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Antioxidant Therapy in RYR1-Related Congenital Myopathy (RYR1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02362425
Recruitment Status : Completed
First Posted : February 13, 2015
Results First Posted : December 24, 2019
Last Update Posted : December 24, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Nursing Research (NINR) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Neuromuscular Disease
Interventions Drug: N-acetylcysteine
Drug: Placebo
Enrollment 63
Recruitment Details  
Pre-assignment Details  
Arm/Group Title RYR1-RM Volunteers Healthy Volunteers RYR1-RM Volunteers: N-acetylcysteine (NAC) RYR1-RM Volunteers: Placebo
Hide Arm/Group Description Subjects with RYR1-RM entered into the Natural History Phase of the study. Healthy volunteers entered into the study for a one-visit assessment; no treatment given. RYR1-RM subjects who were eventually randomized to NAC 900 mg tablets RYR1-RM subjects who were eventually randomized to Placebo 900 mg tablets without active NAC
Period Title: Phase 1 (up to 6 Months)
Started 53 10 0 0
Completed 37 10 0 0
Not Completed 16 0 0 0
Reason Not Completed
Withdrawal by Subject             2             0             0             0
Medicinal contraindication             1             0             0             0
Screening failure             1             0             0             0
Confirmatory genetic testing negative             3             0             0             0
Study closure             9             0             0             0
Period Title: Phase 2 (up to 6 Months, Randomized)
Started 0 0 16 17
Completed 0 0 15 14
Not Completed 0 0 1 3
Reason Not Completed
Adverse Event             0             0             0             2
Withdrawal by Subject             0             0             0             1
Discontinued study drug due to procedure             0             0             1             0
Arm/Group Title RYR1-RM Volunteers Healthy Volunteers RYR1-RM Volunteers: N-acetylcysteine (NAC) RYR1-RM Volunteers :Placebo Total
Hide Arm/Group Description All participants with RYR1-RM enrolled into the natural history period of the trial. Healthy volunteers were evaluated to determine normal values of biomarkers, muscle ultrasound, and near infrared spectroscopy in this rare disease, in order to develop a comparison between healthy and RYR1-RM individuals. N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on participant weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day Placebo 900 mg tablets identical but did not contain NAC Total of all reporting groups
Overall Number of Baseline Participants 53 10 16 17 96
Hide Baseline Analysis Population Description
The baseline analysis population contains the healthy volunteer participants, who only had one visit to determine normal values of biomarkers, muscle ultrasound, and near infrared spectroscopy in this rare disease, in order to develop a comparison between healthy and RYR1-RM individuals.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Phase 1: Natural History Period Number Analyzed 53 participants 10 participants 0 participants 0 participants 63 participants
29.2  (17.5) 44.8  (13.2) 31.7  (17.9)
Phase 2: Randomized Period Number Analyzed 0 participants 0 participants 16 participants 17 participants 33 participants
28.1  (17.4) 26.7  (18.5) 27.4  (17.7)
[1]
Measure Analysis Population Description: Baseline measures are provided for the 53 RYR1-RM participants and the 10 healthy volunteers in the natural history phase, and for the 33 subjects who continued on into the randomized phase.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase 1: Natural History Period Number Analyzed 53 participants 10 participants 0 participants 0 participants 63 participants
Female 29 7 36
Male 24 3 27
Phase 2: Randomized Period Number Analyzed 0 participants 0 participants 16 participants 17 participants 33 participants
Female 9 10 19
Male 7 7 14
[1]
Measure Analysis Population Description: Baseline measures are provided for the 53 RYR1-RM participants and the 10 healthy volunteers in the natural history phase, and for the 33 subjects who continued on into the randomized phase.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase 1: Natural History Period Number Analyzed 53 participants 10 participants 0 participants 0 participants 63 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
  11.3%
2
  20.0%
8
  12.7%
White
47
  88.7%
8
  80.0%
55
  87.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Phase 2: Randomized Period Number Analyzed 0 participants 0 participants 16 participants 17 participants 33 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   6.3%
0
   0.0%
1
   3.0%
White
15
  93.8%
17
 100.0%
32
  97.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: Baseline measures are provided for the 53 RYR1-RM participants and the 10 healthy volunteers in the natural history phase, and for the 33 subjects who continued on into the randomized phase.
Region of Enrollment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 53 participants 10 participants 0 participants 0 participants 63 participants
53
 100.0%
10
 100.0%
0 0
63
 100.0%
[1]
Measure Analysis Population Description: This measure of Region of Enrollment is presented for subjects enrolled in the Natural History phase of the study as well as the Healthy Volunteers.
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 0 participants 0 participants 16 participants 17 participants 33 participants
16 17 33
[1]
Measure Analysis Population Description: This measure of Region of Enrollment is presented for the subjects in the randomized period of the study, ie, randomized population.
Body Mass Index BMI(kg/m^2)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Phase 1: Natural History Period Number Analyzed 53 participants 10 participants 0 participants 0 participants 63 participants
22.1  (8.7) 32.1  (6.1) 24.4  (8.7)
Phase 2: Randomized Period Number Analyzed 0 participants 0 participants 16 participants 17 participants 33 participants
22.8  (8.2) 21.5  (6.5) 21.9  (7.5)
[1]
Measure Analysis Population Description: Baseline measures are provided for the 53 RYR1-RM participants and the 10 healthy volunteers in the natural history phase, and for the 33 subjects who continued on into the randomized phase.
Mode of Inheritance, dominant/de novo   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Phase 1: Natural History Period Number Analyzed 53 participants 0 participants 0 participants 0 participants 53 participants
40 40
Phase 2: Randomized Period Number Analyzed 0 participants 0 participants 16 participants 17 participants 33 participants
12 13 25
[1]
Measure Description: Mode of Inheritance is not applicable to healthy volunteer participants and therefore was not collected.
[2]
Measure Analysis Population Description: Mode of Inheritance is not applicable to healthy volunteer participants and therefore was not collected. Baseline measures are provided for each of the other two parts of the study: natural history and randomized. Of the 53 participants in the natural history period, 33 continued on into the randomized phase.
1.Primary Outcome
Title Urine 15-F2t Isoprostane Concentration
Hide Description Urine will be assayed for 15-isoprostane-F2, which is formed when arachidonic acid reacts with reactive oxygen species(ROS). A validated gas chromatography(GC)-mass spectrometer (MS) method will be used to quantify 15-isoprostane-F2
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers post-baseline (months 6 and 12), thus they are not included in the analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ng/mg Cr
2.7
(1.7 to 3.7)
2.6
(1.5 to 3.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments Null Hypothesis: In RYR1-RM myopathy patients, there will be no statistically significant difference in corrected 15-F2t-isoprostane concentration and/or corrected 15=f2t-Isop:PGR2alpha ratio between NAC and placebo groups at month 12, after controlling for established a priori confounders.
Type of Statistical Test Superiority
Comments An a priori power calculation, with power at 80% and a two-sided α of 0·05, determined that n=76 participants (n=38 per group) would be required to detect a statistically significant post-intervention difference in plasma glutathione (GSH) concentration between NAC and placebo groups. After the primary endpoint was changed, re-evaluation of the sample size determined that a larger sample (total n=182) would be required. As per protocol, the study was completed at this time.
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method Regression, Linear
Comments Model comparing 12 m corrected 15-F2t-isoprostane conc. controlling for pre-intervention value. Investigated covariates: smoking and drinking status.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-1.4 to 1.6
Estimation Comments [Not Specified]
2.Primary Outcome
Title Six Minute Walk Test (6MWT)
Hide Description Meters walked in 6 minutes will be recorded; distances in meters will be recorded at each minute interval; speed will be calculated.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Least Squares Mean (95% Confidence Interval)
Unit of Measure: meters
495.8
(475.8 to 515.9)
471.9
(451.1 to 492.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments In RYR1-RM myopathy patients, there will be no statistically significant difference in 6MWT (six minute walk test) total distance between NAC and placebo groups at month 12, after controlling for established a priori confounders.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .11
Comments Model controlled for six-month(pre-intervention) distance and treatment group. Investigated covariates: height
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 23.9
Confidence Interval (2-Sided) 95%
-5.5 to 53.4
Estimation Comments [Not Specified]
3.Secondary Outcome
Title DCF-fluorescence Intensity (AU)
Hide Description Dichlorodihydrofluorescein (DCFH) will be used on participate muscle biopsies to analyze intracellular oxidant activity [H2DCFDA (H2-DCF, DCF)].
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was performed only on participants in the randomized population who volunteered to have the muscle biopsy performed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 6 4
Mean (95% Confidence Interval)
Unit of Measure: AU
1.9
(0.7 to 3.1)
3.4
(1.7 to 5.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-3.6 to 0.7
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to Ascend Steps (Seconds)
Hide Description Participants completed the following timed function tests: supine to stand, ascend four steps, descend four steps, and walk/run 10 meters. For time taken to ascend four steps, the subject was asked to ascend four steps whilst being timed.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 15 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: seconds
3.2
(2.9 to 3.5)
3.3
(3.0 to 3.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.62
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.5 to 0.3
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Descend Steps
Hide Description Participants completed the following timed function tests: supine to stand, ascend four steps, descend four steps, and walk/run 10 meters. For time taken to descend four steps, the subject was asked to descend four steps whilst being timed.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 15 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: seconds
1.9
(1.5 to 2.3)
2.4
(2.1 to 2.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.1 to 0.0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Walk/Run 10 Meters
Hide Description Participants completed the following timed function tests: supine to stand, ascend four steps, descend four steps, and walk/run 10 meters. For walk/run 10 meters, participants were timed as they walked/ran a marked 10-meter course as quickly as possible.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 15 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: seconds
5.2
(4.3 to 6.1)
5.9
(5.0 to 6.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.1 to 0.6
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Supine to Stand
Hide Description Participants completed the following timed function tests: supine to stand, ascend four steps, descend four steps, and walk/run 10 meters. For time taken to transition from supine to standing, participants were asked to lay supine and then the time taken to move from supine to standing was recorded.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 15 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: seconds
7.4
(6.6 to 8.1)
8.4
(7.7 to 9.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.1 to 0.0
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Motor Function Measure-32 (MFM-32) Domain 1 (D1)
Hide Description Motor Function Measure, MFM-32 is a well-established scale of motor function in congenital muscle disease. The D1 domains measure standard and transfers, and consist of 13 items. Generic Values for each domain are: 0 = cannot perform the task, 1 = initiated the task, 2 - performs the movement incompletely, or completely but imperfectly, 3 = performs the task fully and 'normally'. Total score is the sum of all the domains for D1 divided by the maximum score possible and multiplied by 100. Min=0, Max = 100. Lower numbers on the scale represent a worse outcome.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 15 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: % of maximum score
74.9
(72.1 to 77.6)
71.5
(68.6 to 74.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.09
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.4
Confidence Interval (2-Sided) 95%
-0.6 to 7.3
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Motor Function Measure-32 (MFM-32) Domain 2 (D2)
Hide Description Motor Function Measure, MFM-32 is a well-established scale of motor function in congenital muscle disease. The D2 domains measure axial and proximal motor function and consists of 12 items. Generic Values for each domain are: 0 = cannot perform the task, 1 = initiated the task, 2 - performs the movement incompletely, or completely but imperfectly, 3 = performs the task fully and 'normally'. The total score is the sum of all the MFM-32 domains for D2, divided by maximum score possible and multiplied by 100. Min = 0, Max = 100. Lower numbers on the scale represent a worse outcome.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 15 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: % of maximum score
97.0
(95.9 to 98.1)
96.7
(95.5 to 97.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.3 to 2.0
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Motor Function Measure-32 (MFM-32) Domain 3 (D3)
Hide Description Motor Function Measure, MFM-32 is a well-established scale of motor function in congenital muscle disease. The D3 domains measure distal motor function and consist of 7 items. Generic Values for each domain are: 0 = cannot perform the task, 1 = initiated the task, 2 - performs the movement incompletely, or completely but imperfectly, 3 = performs the task fully and 'normally'. The total score is the sum of all the MFM-32 domains for D3, divided by maximum score possible and multiplied by 100. Min = 0, Max = 100. Lower numbers on the scale represent a worse outcome.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 15 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: % of maximum score
95.5
(93.9 to 97.1)
96.7
(95.0 to 98.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-3.5 to 1.1
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Motor Function Measure-32 (MFM-32) Total Score
Hide Description Motor Function Measure, MFM-32 is a well-established scale of motor function in congenital muscle disease. Generic Values for each domain are: 0 = cannot perform the task, 1 = initiated the task, 2 - performs the movement incompletely, or completely but imperfectly, 3 = performs the task fully and 'normally'. The total score is the sum of all the MFM-32 domains, divided by maximum score possible (96) and multiplied by 100. Min = 0, Max = 100. Lower numbers on the scale represent a worse outcome.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 15 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: % of maximum score
84.1
(82.8 to 85.4)
83.0
(81.7 to 84.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-0.8 to 3.0
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Hand Grip Strength
Hide Description Grip and pinch strength were determined using Myotools dynamometry. The myogrip hand held dynamometer was used to assess grip strength. Higher scores represent better outcomes.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 15 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kg
17.8
(16.1 to 19.5)
17.9
(16.1 to 19.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.93
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-2.6 to 2.4
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Hand Pinch Strength
Hide Description Grip and pinch strength were determined using Myotools dynamometry. The myopinch pinch gauge was used to measure finger strength. Higher scores represent better outcomes.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 15 14
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kg
4.7
(4.0 to 5.5)
4.9
(4.2 to 5.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.3 to 0.8
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Peak Torque Flexion
Hide Description Lower-body isometric strength testing was used to determine peak torque during flexion and extension. Participant's blood pressure was assessed, to rule-out hypertension (>140/90), prior to starting the test. Participants were then asked to push against a stationary arm and remained at the same joint angle for the duration of each test. Two short trials were completed to establish maximal force for each participant. This was followed by a long trial of flexion and extension to capture rate of fatigue to 50% after reaching their pre-determined maximal force. In the interest of safety, participants with hypertension and/or a history of knee injury did not perform the test.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 14 12
Least Squares Mean (95% Confidence Interval)
Unit of Measure: nM
24.7
(23.0 to 26.3)
22.6
(20.8 to 24.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.09
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
-0.4 to 4.6
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Peak Torque Extension
Hide Description Lower-body isometric strength testing was used to determine peak torque during flexion and extension. Participant's blood pressure was assessed, to rule-out hypertension (>140/90), prior to starting the test. Participants were then asked to push against a stationary arm and remained at the same joint angle for the duration of each test. Two short trials were completed to establish maximal force for each participant. This was followed by a long trial of flexion and extension to capture rate of fatigue to 50% after reaching their pre-determined maximal force. In the interest of safety, participants with hypertension and/or a history of knee injury did not perform the test.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 14 12
Least Squares Mean (95% Confidence Interval)
Unit of Measure: nM
24.7
(23.0 to 26.3)
38.8
(35.3 to 42.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.09
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.2
Confidence Interval (2-Sided) 95%
-0.7 to 9.0
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Adult Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue
Hide Description Participants were asked to complete the PROMIS (patient-reported outcomes measurement information system) through the NIH online, self-administered Clinical Trials Survey System. PROMIS scores are normed to 100 meaning that the raw score is converted to a scale where 50 is the mean and the standard deviation is 10. Scores less than 50 indicate less fatigue compared to the average and scores over 50 indicate more fatigue than the average. Lower scores represent better outcomes.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 9 7
Least Squares Mean (95% Confidence Interval)
Unit of Measure: t score
49.5
(43.9 to 55.1)
55.0
(49.5 to 60.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.5
Confidence Interval (2-Sided) 95%
-13.4 to 2.4
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Adult Quality of Life in Neurological Disorders (NeuroQoL) Fatigue
Hide Description Participants were asked to complete the NeuroQoL questionnaire through the NIH online, self-administered Clinical Trials Survey System. The NeuroQoL scores were normed to 100, meaning that the raw score is converted to a scale where 50 is the mean and the standard deviation is 10. Scores less than 50 indicate less fatigue compared to the average and scores over 50 indicate more fatigue than the average. Lower scores represent better outcomes.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 9 7
Least Squares Mean (95% Confidence Interval)
Unit of Measure: t score
45.1
(40.0 to 50.3)
51.5
(46.3 to 56.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.08
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.4
Confidence Interval (2-Sided) 95%
-13.7 to 1.0
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue
Hide Description Participants were asked to complete the PROMIS questionnaire through the NIH online, self-administered Clinical Trials Survey System. PROMIS scores were normed to 100 meaning that the raw scores were converted to a scale where 50 is the mean and the standard deviation is 10. Scores less than 50 indicate less fatigue compared to the average and scores over 50 indicate more fatigue than the average. Lower scores represent better outcomes.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 2 5
Least Squares Mean (95% Confidence Interval)
Unit of Measure: t score
34.8
(18.5 to 88.2)
51.1
(30.9 to 71.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -16.27
Confidence Interval (2-Sided) 95%
-80.1 to 47.5
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Pediatric Quality of Life in Neurological Disorders (NeuroQoL) Fatigue
Hide Description Participants were asked to complete the NeuroQoL questionnaire through the NIH online, self-administered Clinical Trials Survey System. NeuroQoL scores were normed to 100 meaning that the raw score is converted to a scale where 50 is the mean and the standard deviation is 10. Scores less than 50 indicate less fatigue compared to the average and scores over 50 indicate more fatigue than the average. Lower scores represent better outcomes.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 2 5
Least Squares Mean (95% Confidence Interval)
Unit of Measure: t score
43.1
(0.7 to 85.5)
53.1
(40.4 to 65.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.0
Confidence Interval (2-Sided) 95%
-59.5 to 39.5
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Multidimensional Fatigue Inventory - 20 (MFI-20) General Fatigue Score
Hide Description Participants were asked to complete the MFI-20 questionnaire through the NIH online, self-administered Clinical Trials Survey System. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Values range from 4-20 for each scale. Higher scores represent increased fatigue/ worse outcome.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 14 12
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
11.6
(9.7 to 13.5)
13.7
(11.7 to 15.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-5.0 to 0.6
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Multidimensional Fatigue Inventory-20 (MFI-20) Physical Fatigue Score
Hide Description Participants were asked to complete the MFI-20 questionnaire through the NIH online, self-administered Clinical Trials Survey System. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Values range from 4-20 for each scale. Higher scores represent increased fatigue/ worse outcome.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 14 12
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
11.5
(9.3 to 13.6)
11.9
(9.7 to 14.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-3.6 to 2.7
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Multidimensional Fatigue Inventory-20 (MFI-20) Reduced Activity Score
Hide Description Participants were asked to complete the MFI-20 questionnaire through the NIH online, self-administered Clinical Trials Survey System. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Values range from 4-20 for each scale. Higher scores represent increased fatigue/ worse outcome.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 14 12
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
9.2
(7.2 to 11.2)
8.7
(6.6 to 10.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-2.5 to 3.5
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Multidimensional Fatigue Inventory-20 (MFI-20) Reduced Motivation Score
Hide Description Participants were asked to complete the MFI-20 questionnaire through the NIH online, self-administered Clinical Trials Survey System. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Values range from 4-20 for each scale. Higher scores represent increased fatigue/ worse outcome.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 14 12
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
7.8
(6.2 to 9.4)
7.4
(5.7 to 9.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.70
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.8 to 2.7
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Multidimensional Fatigue Inventory-20 (MFI-20) Mental Fatigue Score
Hide Description Participants were asked to complete the MFI-20 questionnaire through the NIH online, self-administered Clinical Trials Survey System. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Values range from 4-20 for each scale. Higher scores represent increased fatigue/ worse outcome.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 14 12
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
8.8
(6.7 to 10.9)
8.6
(6.4 to 10.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-2.8 to 3.3
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score
Hide Description Participants were asked to complete the FACIT-f questionnaire through the NIH online, self-administered Clinical Trials Survey System. Minimum value = 0, maximum value = 160. Higher scores represent a better outcome/ better QOL.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 9 7
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
76.1
(67.7 to 84.5)
73.6
(64.1 to 83.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.5
Confidence Interval (2-Sided) 95%
-10.3 to 15.2
Estimation Comments [Not Specified]
26.Secondary Outcome
Title Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Trial Outcome Index
Hide Description Participants were asked to complete the FACIT-F questionnaire through the NIH online, self-administered Clinical Trials Survey System. The Trial Outcome Index (TOI) is the sum of the physical well-being, functional well-being and 'additional concerns' subscales. The minimum value = 0, and maximum value = 52. Scores under 30 is considered to be severe fatigue. Higher scores represent a better outcome/QOL.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 9 7
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
37.6
(32.3 to 42.8)
37.0
(31.0 to 42.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.87
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-7.4 to 8.5
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Pediatric Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score
Hide Description Pediatric participants (< 18 years) were asked to complete the Peds-FACIT-F questionnaire through the NIH online, self-administered Clinical Trials Survey System.Minimum value = 0, maximum value = 52. Higher scores represent a better outcome/ better QOL.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 6 6
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
29.8
(12.0 to 47.6)
42.3
(30.4 to 54.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetylcysteine (NAC), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -12.5
Confidence Interval (2-Sided) 95%
-38.9 to 13.9
Estimation Comments [Not Specified]
28.Secondary Outcome
Title Blood Glutathione Reduced (GSH):Oxidized (GSSG) Ratio
Hide Description GSH:GSSG ratio analyzed only at baseline to offer comparison of RYR1-RM affected individuals to the general population.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title RYR1-RM Volunteers Healthy Volunteer
Hide Arm/Group Description:
All participants with RYR1-RM enrolled into the natural history period of the trial.
Healthy volunteers who participated in a one-visit assessment.
Overall Number of Participants Analyzed 38 10
Mean (Standard Deviation)
Unit of Measure: ratio
10.8  (7.2) 0.54  (1.18)
29.Other Pre-specified Outcome
Title Urine 15-F2t Isoprostane Concentration Pre-Intervention
Hide Description Urine will be assayed for 15-isoprostane-F2, which is formed when arachidonic acid reacts with reactive oxygen species(ROS). A validated gas chromatography(GC)-mass spectrometer (MS) method will be used to quantify 15-isoprostane-F2
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers post baseline, thus they are not included in this analysis..
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: ng/mg Cr
3.6  (2.2) 3.1  (1.9)
30.Other Pre-specified Outcome
Title Six Minute Walk Test (6MWT) Pre-Intervention
Hide Description Meters walked in 6 minutes will be recorded; distances in meters will be recorded at each minute interval; speed will be calculated.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: meters
519.1  (119.0) 453.8  (128.5)
31.Other Pre-specified Outcome
Title DCF-fluorescence Intensity (AU) Pre-Intervention
Hide Description Dichlorodihydrofluorescein (DCFH) will be used on participate muscle biopsies to analyze intracellular oxidant activity [H2DCFDA (H2-DCF, DCF)].
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was performed only on participants in the randomized population who volunteered to have the muscle biopsy performed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 7 5
Mean (Standard Deviation)
Unit of Measure: AU
1.7  (0.9) 2.0  (1.6)
32.Other Pre-specified Outcome
Title Time to Ascend Steps (Seconds) Pre-Intervention
Hide Description Participants completed the following timed function tests: supine to stand, ascend four steps, descend four steps, and walk/run 10 meters. For time taken to ascend four steps, the subject was asked to ascend four steps whilst being timed.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: seconds
2.9  (1.5) 3.4  (1.8)
33.Other Pre-specified Outcome
Title Descend Steps Pre-Intervention
Hide Description Participants completed the following timed function tests: supine to stand, ascend four steps, descend four steps, and walk/run 10 meters. For time taken to descend four steps, the subject was asked to descend four steps whilst being timed.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: seconds
2.2  (1.0) 2.3  (1.0)
34.Other Pre-specified Outcome
Title Walk/Run 10 Meters Pre-Intervention
Hide Description Participants completed the following timed function tests: supine to stand, ascend four steps, descend four steps, and walk/run 10 meters. For walk/run 10 meters, participants were timed as they walked/ran a marked 10-meter course as quickly as possible.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 15
Mean (Standard Deviation)
Unit of Measure: seconds
5.0  (2.2) 4.6  (1.7)
35.Other Pre-specified Outcome
Title Supine to Stand Pre-Intervention
Hide Description Participants completed the following timed function tests: supine to stand, ascend four steps, descend four steps, and walk/run 10 meters. For time taken to transition from supine to standing, participants were asked to lay supine and then the time taken to move from supine to standing was recorded.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 15
Mean (Standard Deviation)
Unit of Measure: seconds
6.9  (5.5) 6.7  (5.4)
36.Other Pre-specified Outcome
Title Motor Function Measure-32 (MFM-32) Domain 1 (D1) Pre-Intervention
Hide Description Motor Function Measure, MFM-32 is a well-established scale of motor function in congenital muscle disease. The D1 domains measure standard and transfers, and consist of 13 items. Generic Values for each domain are: 0 = cannot perform the task, 1 = initiated the task, 2 - performs the movement incompletely, or completely but imperfectly, 3 = performs the task fully and 'normally'. Total score is the sum of all the domains for D1 divided by the maximum score possible and multiplied by 100. Min=0, Max = 100. Lower numbers on the scale represent a worse outcome.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: % of maximum score
75.8  (16.6) 71.6  (21.2)
37.Other Pre-specified Outcome
Title Motor Function Measure-32 (MFM-32) Domain 2 (D2) Pre-Intervention
Hide Description Motor Function Measure, MFM-32 is a well-established scale of motor function in congenital muscle disease. The D2 domains measure axial and proximal motor function and consists of 12 items. Generic Values for each domain are: 0 = cannot perform the task, 1 = initiated the task, 2 - performs the movement incompletely, or completely but imperfectly, 3 = performs the task fully and 'normally'. The total score is the sum of all the MFM-32 domains for D2, divided by maximum score possible and multiplied by 100. Min = 0, Max = 100. Lower numbers on the scale represent a worse outcome.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis..
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: % of maximum score
96.0  (4.8) 96.6  (7.3)
38.Other Pre-specified Outcome
Title Motor Function Measure-32 (MFM-32) Domain 3 (D3) Pre-Intervention
Hide Description Motor Function Measure, MFM-32 is a well-established scale of motor function in congenital muscle disease. The D3 domains measure distal motor function and consist of 7 items. Generic Values for each domain are: 0 = cannot perform the task, 1 = initiated the task, 2 - performs the movement incompletely, or completely but imperfectly, 3 = performs the task fully and 'normally'. The total score is the sum of all the MFM-32 domains for D3, divided by maximum score possible and multiplied by 100. Min = 0, Max = 100. Lower numbers on the scale represent a worse outcome.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: % of maximum score
96.7  (3.8) 95.2  (5.3)
39.Other Pre-specified Outcome
Title Motor Function Measure-32 (MFM-32) Total Score Pre-Intervention
Hide Description Motor Function Measure, MFM-32 is a well-established scale of motor function in congenital muscle disease. Generic Values for each domain are: 0 = cannot perform the task, 1 = initiated the task, 2 - performs the movement incompletely, or completely but imperfectly, 3 = performs the task fully and 'normally'. The total score is the sum of all the MFM-32 domains, divided by maximum score possible (96) and multiplied by 100. Min = 0, Max = 100. Lower numbers on the scale represent a worse outcome.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: % of maximum score
84.4  (7.6) 82.7  (9.8)
40.Other Pre-specified Outcome
Title Hand Grip Strength Pre-Intervention
Hide Description Grip and pinch strength were determined using Myotools dynamometry. The myogrip hand held dynamometer was used to assess grip strength. Higher scores represent better outcomes.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: kg
20.5  (14.0) 17.5  (11.0)
41.Other Pre-specified Outcome
Title Hand Pinch Strength Pre-Intervention
Hide Description Grip and pinch strength were determined using Myotools dynamometry. The myopinch pinch gauge was used to measure finger strength. Higher scores represent better outcomes.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: kg
6.5  (5.0) 5.1  (2.3)
42.Other Pre-specified Outcome
Title Peak Torque Flexion Pre-Intervention
Hide Description Lower-body isometric strength testing was used to determine peak torque during flexion and extension. Participant's blood pressure was assessed, to rule-out hypertension (>140/90), prior to starting the test. Participants were then asked to push against a stationary arm and remained at the same joint angle for the duration of each test. Two short trials were completed to establish maximal force for each participant. This was followed by a long trial of flexion and extension to capture rate of fatigue to 50% after reaching their pre-determined maximal force. In the interest of safety, participants with hypertension and/or a history of knee injury did not perform the test.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 14
Mean (Standard Deviation)
Unit of Measure: nM
31.9  (22.0) 25.2  (21.3)
43.Other Pre-specified Outcome
Title Peak Torque Extension Pre-Intervention
Hide Description Lower-body isometric strength testing was used to determine peak torque during flexion and extension. Participant's blood pressure was assessed, to rule-out hypertension (>140/90), prior to starting the test. Participants were then asked to push against a stationary arm and remained at the same joint angle for the duration of each test. Two short trials were completed to establish maximal force for each participant. This was followed by a long trial of flexion and extension to capture rate of fatigue to 50% after reaching their pre-determined maximal force. In the interest of safety, participants with hypertension and/or a history of knee injury did not perform the test.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 16 14
Mean (Standard Deviation)
Unit of Measure: nM
56.9  (42.9) 41.6  (45.5)
44.Other Pre-specified Outcome
Title Adult Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue Pre-Intervention
Hide Description Participants were asked to complete the PROMIS (patient-reported outcomes measurement information system) through the NIH online, self-administered Clinical Trials Survey System. PROMIS scores are normed to 100 meaning that the raw score is converted to a scale where 50 is the mean and the standard deviation is 10. Scores less than 50 indicate less fatigue compared to the average and scores over 50 indicate more fatigue than the average. Lower scores represent better outcomes.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 7 10
Mean (Standard Deviation)
Unit of Measure: t score
59.2  (11.8) 58.5  (11.3)
45.Other Pre-specified Outcome
Title Adult Quality of Life in Neurological Disorders (NeuroQoL) Fatigue Pre-Intervention
Hide Description Participants were asked to complete the NeuroQoL questionnaire through the NIH online, self-administered Clinical Trials Survey System. The NeuroQoL scores were normed to 100, meaning that the raw score is converted to a scale where 50 is the mean and the standard deviation is 10. Scores less than 50 indicate less fatigue compared to the average and scores over 50 indicate more fatigue than the average. Lower scores represent better outcomes.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 7 10
Mean (Standard Deviation)
Unit of Measure: t score
53.25  (8.5) 51.9  (7.4)
46.Other Pre-specified Outcome
Title Pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Pre-Intervention
Hide Description Participants were asked to complete the PROMIS questionnaire through the NIH online, self-administered Clinical Trials Survey System. PROMIS scores were normed to 100 meaning that the raw scores were converted to a scale where 50 is the mean and the standard deviation is 10. Scores less than 50 indicate less fatigue compared to the average and scores over 50 indicate more fatigue than the average. Lower scores represent better outcomes.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 4 4
Mean (Standard Deviation)
Unit of Measure: t score
42.6  (8.4) 57.3  (7.7)
47.Other Pre-specified Outcome
Title Pediatric Quality of Life in Neurological Disorders (NeuroQoL) Fatigue Pre-Intervention
Hide Description Participants were asked to complete the NeuroQoL questionnaire through the NIH online, self-administered Clinical Trials Survey System. NeuroQoL scores were normed to 100 meaning that the raw score is converted to a scale where 50 is the mean and the standard deviation is 10. Scores less than 50 indicate less fatigue compared to the average and scores over 50 indicate more fatigue than the average. Lower scores represent better outcomes.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 4 5
Mean (Standard Deviation)
Unit of Measure: t score
45.9  (6.4) 52.8  (2.8)
48.Other Pre-specified Outcome
Title Multidimensional Fatigue Inventory - 20 (MFI-20) General Fatigue Score Pre-Intervention
Hide Description Participants were asked to complete the MFI-20 questionnaire through the NIH online, self-administered Clinical Trials Survey System. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Values range from 4-20 for each scale. Higher scores represent increased fatigue/ worse outcome.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 13 15
Mean (Standard Deviation)
Unit of Measure: scores on a scale
12.9  (4.2) 14.3  (3.8)
49.Other Pre-specified Outcome
Title Multidimensional Fatigue Inventory-20 (MFI-20) Physical Fatigue Score Pre-Intervention
Hide Description Participants were asked to complete the MFI-20 questionnaire through the NIH online, self-administered Clinical Trials Survey System. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Values range from 4-20 for each scale. Higher scores represent increased fatigue/ worse outcome.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 13 15
Mean (Standard Deviation)
Unit of Measure: scores on a scale
12.1  (5.6) 13.0  (3.9)
50.Other Pre-specified Outcome
Title Multidimensional Fatigue Inventory-20 (MFI-20) Reduced Activity Score Pre-Intervention
Hide Description Participants were asked to complete the MFI-20 questionnaire through the NIH online, self-administered Clinical Trials Survey System. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Values range from 4-20 for each scale. Higher scores represent increased fatigue/ worse outcome.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 13 15
Mean (Standard Deviation)
Unit of Measure: scores on a scale
9.5  (4.7) 11.3  (3.2)
51.Other Pre-specified Outcome
Title Multidimensional Fatigue Inventory-20 (MFI-20) Reduced Motivation Score Pre-Intervention
Hide Description Participants were asked to complete the MFI-20 questionnaire through the NIH online, self-administered Clinical Trials Survey System. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Values range from 4-20 for each scale. Higher scores represent increased fatigue/ worse outcome.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 13 15
Mean (Standard Deviation)
Unit of Measure: scores on a scale
7.9  (3.1) 9.1  (3.5)
52.Other Pre-specified Outcome
Title Multidimensional Fatigue Inventory-20 (MFI-20) Mental Fatigue Score Pre-Intervention
Hide Description Participants were asked to complete the MFI-20 questionnaire through the NIH online, self-administered Clinical Trials Survey System. The MFI consists of 5 subscales: general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation. Values range from 4-20 for each scale. Higher scores represent increased fatigue/ worse outcome.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 13 15
Mean (Standard Deviation)
Unit of Measure: scores on a scale
8.8  (4.8) 9.7  (4.4)
53.Other Pre-specified Outcome
Title Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score Pre-Intervention
Hide Description Participants were asked to complete the FACIT-f questionnaire through the NIH online, self-administered Clinical Trials Survey System. Minimum value = 0, maximum value = 160. Higher scores represent a better outcome/ better QOL.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
69.2  (16.9) 71.3  (20.9)
54.Other Pre-specified Outcome
Title Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Trial Outcome Index Pre-Intervention
Hide Description Participants were asked to complete the FACIT-F questionnaire through the NIH online, self-administered Clinical Trials Survey System. The Trial Outcome Index (TOI) is the sum of the physical well-being, functional well-being and 'additional concerns' subscales. The minimum value = 0, and maximum value = 52. Scores under 30 is considered to be severe fatigue. Higher scores represent a better outcome/QOL.
Time Frame 6 months
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Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: scores on a scale
33.8  (11.4) 34.3  (10.3)
55.Other Pre-specified Outcome
Title Pediatric Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score Pre-Intervention
Hide Description Pediatric participants (< 18 years) were asked to complete the Peds-FACIT-F questionnaire through the NIH online, self-administered Clinical Trials Survey System.Minimum value = 0, maximum value = 52. Higher scores represent a better outcome/ better QOL.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Outcome measures are reported for participants who were randomized and continued into the randomized, double-blind period of the trial. Missing data was not imputed. This measure was not collected for Healthy Volunteers, thus they are not included in this analysis.
Arm/Group Title N-acetylcysteine (NAC) Placebo
Hide Arm/Group Description:
N-acetylcysteine (NAC) 900 mg tablets; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day
Placebo 900 mg tablets identical but did not contain NAC
Overall Number of Participants Analyzed 5 4
Mean (Standard Deviation)
Unit of Measure: scores on a scale
43.2  (7.7) 37.0  (8.4)
56.Other Pre-specified Outcome
Title Urine 15-F2t Isoprostane Concentration at Baseline
Hide Description Urine will be assayed for 15-isoprostane-F2, which is formed when arachidonic acid reacts with reactive oxygen species(ROS). A validated gas chromatography(GC)-mass spectrometer (MS) method will be used to quantify 15-isoprostane-F2
Time Frame Baseline
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Hide Analysis Population Description
Healthy volunteers who participated in a one-visit assessment and RYR1-RM Volunteers measured at Baseline.
Arm/Group Title RYR1-RM Volunteers Healthy Volunteers
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All participants with RYR1-RM enrolled into the natural history period of the trial.
Healthy volunteers entered into the study for a one-visit assessment; no treatment given.
Overall Number of Participants Analyzed 49 10
Mean (Standard Deviation)
Unit of Measure: ng/mg Cr
3.17  (1.48) 1.36  (0.48)
Time Frame Adverse events (AE) were collected from start of study drug through the end of the study at 12 months. AEs were analyzed for the natural history period and the treatment period separately.
Adverse Event Reporting Description (Institutional Review Board) IRB determination was used for the classification of adverse events
 
Arm/Group Title RYR1-RM Volunteers RYR1-RM Volunteers: N-acetylcysteine (NAC) RYR1-RM Volunteers :Placebo Healthy Volunteers
Hide Arm/Group Description All participants with RYR1-RM enrolled into the natural history period of the trial N-acetylcysteine (NAC) 900 mg tablets for 6 months; week 1 up to 1800 mg/day; Week 2- through end of study based on subject weight: < 50 kg subjects up to 2700 mg/day, >50 kg subjects 2700 mg/day Placebo 900 mg tablets for 6 months; identical but did not contain NAC Healthy volunteers were evaluated at a one-visit assessment at baseline to determine normal values of biomarkers, muscle ultrasound, and near infrared spectroscopy in order to develop a comparison between healthy and RYR1-RM individuals
All-Cause Mortality
RYR1-RM Volunteers RYR1-RM Volunteers: N-acetylcysteine (NAC) RYR1-RM Volunteers :Placebo Healthy Volunteers
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/53 (0.00%)   0/16 (0.00%)   0/17 (0.00%)   0/10 (0.00%) 
Hide Serious Adverse Events
RYR1-RM Volunteers RYR1-RM Volunteers: N-acetylcysteine (NAC) RYR1-RM Volunteers :Placebo Healthy Volunteers
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/53 (1.89%)   4/16 (25.00%)   5/17 (29.41%)   0/10 (0.00%) 
Congenital, familial and genetic disorders         
Intestinal Malrotation  1  1/53 (1.89%)  1/16 (6.25%)  0/17 (0.00%)  /10 
Gastrointestinal disorders         
Diarrhoea  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  /10 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  /10 
Reproductive system and breast disorders         
Uterine Leiomyoma  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  /10 
Ovarian Cyst  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  /10 
Respiratory, thoracic and mediastinal disorders         
Asthma  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  /10 
Chest Discomfort  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  /10 
Vascular disorders         
Hypotension  1  0/53 (0.00%)  1/16 (6.25%)  1/17 (5.88%)  /10 
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
RYR1-RM Volunteers RYR1-RM Volunteers: N-acetylcysteine (NAC) RYR1-RM Volunteers :Placebo Healthy Volunteers
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   36/53 (67.92%)   16/16 (100.00%)   17/17 (100.00%)   5/10 (50.00%) 
Blood and lymphatic system disorders         
Left inguinal lymph node  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Congenital, familial and genetic disorders         
Malrotation of bowel  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Eye disorders         
Blurred Vision  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Gastrointestinal disorders         
Barrett's Oesophagus  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Stomach Virus  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Diarrhoea  1  0/53 (0.00%)  2/16 (12.50%)  3/17 (17.65%)  0/10 (0.00%) 
Constipation  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Faecal Incontinence  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Abdominal Distension  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Nausea  1  1/53 (1.89%)  1/16 (6.25%)  4/17 (23.53%)  0/10 (0.00%) 
Vomiting  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Abdominal Pain Upper  1  0/53 (0.00%)  1/16 (6.25%)  1/17 (5.88%)  0/10 (0.00%) 
Dry Mouth  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Abdominal pain  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
General disorders         
Influenza-like Illness  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Pyrexia  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Pain  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Infections and infestations         
Infection  1  0/53 (0.00%)  0/16 (0.00%)  2/17 (11.76%)  0/10 (0.00%) 
Upper Respiratory Tract Infection  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Injury, poisoning and procedural complications         
Fall  1  2/53 (3.77%)  5/16 (31.25%)  2/17 (11.76%)  0/10 (0.00%) 
Joint Dislocation  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Investigations         
Gamma-glutamyl Transferase Increased  1  1/53 (1.89%)  2/16 (12.50%)  0/17 (0.00%)  0/10 (0.00%) 
Alanine Aminotransferase Increased  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  1/10 (10.00%) 
Prothombin Time Prolonged  1  0/53 (0.00%)  0/16 (0.00%)  2/17 (11.76%)  0/10 (0.00%) 
Red Cell Distribution Width Increased  1  1/53 (1.89%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Activated Partial Thromboplastin Time Prolonged  1  1/53 (1.89%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Blood Creatinine Phosphokinase Increased  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Blood Creatinine Decreased  1  5/53 (9.43%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Blood Pressure Increased  1  0/53 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Hematocrit increased  1  2/53 (3.77%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Hemoglobin increased  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Mean corpuscular volume increased  1  2/53 (3.77%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
mean corpuscular hemoglobin concentration decreased  1  2/53 (3.77%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
C-reactive protein increased  1  3/53 (5.66%)  0/16 (0.00%)  0/17 (0.00%)  2/10 (20.00%) 
Creatinine kinase increased  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
White blood cell count increased  1  2/53 (3.77%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
White blood cell count decreased  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  1/10 (10.00%) 
Alkaline phosphatase increased  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Mean Platelet Volume (MVP) low  1  0/53 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  1/10 (10.00%) 
Bilirubin high  1  0/53 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  1/10 (10.00%) 
Aspartate Aminotransferase Increased  1  0/53 (0.00%)  0/16 (0.00%)  0/17 (0.00%)  1/10 (10.00%) 
Metabolism and nutrition disorders         
Dehydration  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Musculoskeletal and connective tissue disorders         
Myalgia  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Arthrosis  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Bone island benign tumor  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Bursitis  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Enchondroma  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Malignant Melanoma  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Nervous system disorders         
Headache  1  0/53 (0.00%)  0/16 (0.00%)  2/17 (11.76%)  0/10 (0.00%) 
Migraine  1  0/53 (0.00%)  0/16 (0.00%)  3/17 (17.65%)  0/10 (0.00%) 
Memory Impairment  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Dizziness  1  0/53 (0.00%)  0/16 (0.00%)  2/17 (11.76%)  0/10 (0.00%) 
Reproductive system and breast disorders         
Menorrhagia  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Inguinal hernia  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Ovarian cyst  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Uterine fibroids  1  1/53 (1.89%)  0/16 (0.00%)  0/17 (0.00%)  0/10 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Asthma  1  0/53 (0.00%)  1/16 (6.25%)  1/17 (5.88%)  0/10 (0.00%) 
Skin and subcutaneous tissue disorders         
Night Sweats  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
Pruritis  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Urticaria  1  0/53 (0.00%)  0/16 (0.00%)  1/17 (5.88%)  0/10 (0.00%) 
Vascular disorders         
Flushing  1  0/53 (0.00%)  1/16 (6.25%)  0/17 (0.00%)  0/10 (0.00%) 
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Katherine Meileur Chief, Neuromuscular Symptoms Unit
Organization: National Institute of Nursing
Phone: 301-435-1503
EMail: meilleurk@mail.nih.gov
Layout table for additonal information
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Nursing Research (NINR) )
ClinicalTrials.gov Identifier: NCT02362425    
Other Study ID Numbers: 150072
15-NR-0072
First Submitted: February 12, 2015
First Posted: February 13, 2015
Results First Submitted: March 27, 2019
Results First Posted: December 24, 2019
Last Update Posted: December 24, 2019