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N-Acetyl-Cysteine (NAC) in Early Phase Schizophrenia Spectrum Psychosis (NACPSY)

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: NCT01354132
Recruitment Status : Completed
First Posted : May 16, 2011
Results First Posted : June 7, 2017
Last Update Posted : July 5, 2017
Sponsor:
Collaborator:
Center de Neurosciences Psychiatrique, Lausanne, Switzerland
Information provided by (Responsible Party):
Larry Seidman, Beth Israel Deaconess Medical Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Schizophrenic Psychoses
Interventions Drug: n-acetylcysteine
Drug: Placebo
Enrollment 20
Recruitment Details Participants were recruited at two sites, Lausanne University Hospital, Department of Psychiatry, Lausanne, Switzerland and at the Commonwealth Research Center of Beth Israel Deaconess Medical Center Boston, Massachusetts
Pre-assignment Details 320 signed consent 133 declined to participate 124 excluded - 65 by Physician decision, 59 subject withdrew 63 met all inclusion and no exclusion criteria 31 to NAC and 30 to placebo
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Period Title: Randomization
Started 32 [1] 31 [2]
Completed 31 30
Not Completed 1 1
Reason Not Completed
Physician Decision             1             0
Withdrawal by Subject             0             1
[1]
1 never took study medication dropped by physician decision (White matter lesion on MRI)
[2]
1 never took study medication due to subject withdrawal
Period Title: Double Blind (Visits 1-7)
Started 31 [1] 30 [2]
Completed More Than 1 Visit 4 5
Stopped After First Visit 3 2
Didn't Complete at Least 1 Visit 2 4
Completed 22 19
Not Completed 9 11
Reason Not Completed
Adverse Event             1             0
Withdrawal by Subject             8             11
[1]
9 did not compete 7 study visits
[2]
11 did not compete 7 study visits
Period Title: 1 Month Post Study Medication
Started 22 19
1 Follow-up Visit (Visit 8) 21 16
Completed 21 16
Not Completed 1 3
Reason Not Completed
Withdrawal by Subject             1             3
Arm/Group Title N-acetyl-cysteine Placebo Total
Hide Arm/Group Description

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Total of all reporting groups
Overall Number of Baseline Participants 31 30 61
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants 30 participants 61 participants
26.1  (6.1) 24.7  (5.9) 25.4  (6.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 30 participants 61 participants
Female
5
  16.1%
9
  30.0%
14
  23.0%
Male
26
  83.9%
21
  70.0%
47
  77.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Black or African American Number Analyzed 31 participants 30 participants 61 participants
5 7 12
White Number Analyzed 31 participants 30 participants 61 participants
25 22 47
Maghreb Number Analyzed 31 participants 30 participants 61 participants
1 1 2
Hispanic or Latino Number Analyzed 31 participants 30 participants 61 participants
0 1 1
Not Hispanic or Latino Number Analyzed 31 participants 30 participants 61 participants
31 29 60
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 31 participants 30 participants 61 participants
6
  19.4%
4
  13.3%
10
  16.4%
Switzerland Number Analyzed 31 participants 30 participants 61 participants
26
  83.9%
27
  90.0%
53
  86.9%
Positive and Negative Symptom Scale (PANSS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Positive PANSS Symptoms Number Analyzed 31 participants 30 participants 61 participants
14.3  (5.4) 15.0  (5.6) 14.7  (16.4)
Negative Symptoms Number Analyzed 31 participants 30 participants 61 participants
15.6  (5.0) 17.3  (6.3) 16.4  (5.7)
[1]
Measure Description:

Clinical Measure of Positive (7 items P1-P7) Negative Symptoms (7 items N1-N7) General Psychopathology Symptoms (G1-G16) total of 30 items

Assessed in the previous week:

RATING SCALE

1: Absent 2: Minimal 3: Mild 4: Moderate 5: Moderate Severe 6: Severe 7: Extreme The higher the score the worse the symptoms. The lowest possible score is 30 and the highesr possible score is 210.

Global Assessment of Functioning (GAF)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 31 participants 30 participants 61 participants
54  (10.8) 51.6  (12.8) 52.8  (11.8)
[1]
Measure Description:

Clinical Measure of Global level of Symptoms (Sx) and Functioning from 1 (Worst) to 100 (Best) in groups of 10:

100 – 91: Superior functioning 90 – 81: Absent or minimal Sx 80 – 71: If symptoms are present and expected 70 – 61:Some mild Sx 60 – 51: Moderate Sx 50 – 41: Serious Sx 40 – 31: Some impairment in reality testing or communication 30 – 21: Behavior is considerably influenced by delusions or hallucinations 20 – 11: Some danger of hurting self or others 10 – 1: Persistent danger of severely hurting self or others

Duration of Psychosis   [1] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 31 participants 30 participants 61 participants
848  (767) 747  (693) 796  (726)
[1]
Measure Description: Duration of time in days since onset of psychosis
Social and Occupational Functioning Assessment Scale (SOFAS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 31 participants 30 participants 61 participants
55.8  (11.0) 53.5  (13.0) 54.7  (12.0)
[1]
Measure Description:

Rating of Overall Social and Occupational Functioning on a scale of 1 (worst) to 100 (best) in groups of 10:

100–91: Superior functioning 90–81: Good functioning 80–71: Slight impairment 70–61: Some difficulty 60–51: Moderate difficulty 50–41: Serious impairment 40–31: Major impairment 30–21: Inability to function in almost all areas 20–11: Unable to function independently 10–1: Unable to function without harming self or others

MATRICS Consensus Cognitive Battery (MCCB) excluding MISCEIT managing emotions test)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Standardized T Scores
Processing Speed Number Analyzed 20 participants 16 participants 36 participants
37.72  (11.22) 35.53  (16.31) 36.75  (13.48)
Sustained Attention Number Analyzed 20 participants 16 participants 36 participants
40.23  (11.71) 32.67  (13.15) 36.87  (12.35)
Working Memory Number Analyzed 20 participants 16 participants 36 participants
47.56  (9.70) 38.87  (15.09) 43.70  (12.10)
Verbal Learning Number Analyzed 20 participants 16 participants 36 participants
40.94  (10.09) 40.93  (13.73) 40.94  (11.71)
Visual Learning Number Analyzed 20 participants 16 participants 36 participants
41.06  (10.01) 44.86  (14.42) 42.75  (11.97)
Problem Solving Number Analyzed 20 participants 16 participants 36 participants
48.00  (11.69) 39.93  (12.76) 44.41  (12.17)
[1]
Measure Description: The MCCB has 6 cognitive factors including: 1) processing speed (Trail Making Test, BACS: Symbol Coding, Category Fluency: Animal Naming), 2) sustained attention (Continuous Performance Test –Identical Pairs), 3) working memory (WMS-III Spatial Span and Letter-Number Span), 4) verbal learning (Hopkins Verbal Learning Test-Revised: Immediate Recall), 5) visual learning (Brief Visuospatial Memory test – Revised: Immediate Recall) and 6) problem solving (NAB Mazes). The T-score of 50 is an average score. Scores below 50 indicates cognitive processing lower than age matched healthy populations.
[2]
Measure Analysis Population Description: Numbers in each group analyzed based on those who completed baseline and post testing.
Antipsychotic Medication Chlorpromazine Equivalents   [1] 
Mean (Standard Deviation)
Unit of measure:  Milligrams
Number Analyzed 31 participants 30 participants 61 participants
309  (252) 309  (188) 309  (220)
[1]
Measure Description: Dose of current antipsychotic medication in chlorpromazine equivalents
Blood Marker - Cysteine   [1] 
Mean (Standard Deviation)
Unit of measure:  uM (micrometer)
Number Analyzed 31 participants 30 participants 61 participants
261.3  (37.6) 254.0  (33.6) 257.7  (35.7)
[1]
Measure Description: Cysteine is an amino acid, a building block for proteins and is used throughout the body and was measured in blood plasma.
Blood Marker - GPxbc- Glutathione peroxidase   [1] 
Mean (Standard Deviation)
Unit of measure:  umol/min/gHb
Number Analyzed 31 participants 30 participants 61 participants
21.24  (7.5) 21.01  (6.93) 21.13  (7.17)
[1]
Measure Description: GPxBC is a measurement of glutathiione peroxidase enzymatic activity in glutathione synthesis and the redox system in blood cells. Measured as umol/min/gHb from blood cells.
Blood Marker - Glutathione   [1] 
Mean (Standard Deviation)
Unit of measure:  mM (millimolar) in blood cells
Number Analyzed 31 participants 30 participants 61 participants
0.77  (0.21) 0.84  (0.27) 0.81  (0.24)
[1]
Measure Description: Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids. The level of glutathione is measured in blood cells.
Brain Marker - Glutamine and myo-Inositol   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mM (millimolar)
Glutamine Number Analyzed 13 participants 12 participants 25 participants
3.25  (0.51) 2.93  (0.48) 3.10  (0.50)
Myo-Inositol Number Analyzed 13 participants 12 participants 25 participants
6.25  (1.05) 6.28  (0.62) 6.26  (0.84)
[1]
Measure Description: Brain levels of glutamine and myo-Inositol were measured using Magnetic ResonanceSpectroscopy (H-MRS), both are chemicals that work to protect the brain from high levels of excitatory chemicals such as glutamate.
[2]
Measure Analysis Population Description: MRS was completed on fewer participants.
Brain Marker - Glutathione and Glutamate   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  mM (millimolar)
Glutathione Number Analyzed 13 participants 12 participants 25 participants
0.87  (0.23) 1.12  (0.18) 0.99  (0.21)
Glutamate Number Analyzed 13 participants 12 participants 25 participants
10.12  (0.80) 10.64  (1.23) 10.37  (1.01)
[1]
Measure Description: Brain markers, glutathione and glutamate were measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids. Glutamate is an excitatory neurotransmitter in the brain.
[2]
Measure Analysis Population Description: Only 25 participants had the MRS.
1.Primary Outcome
Title Change in Negative Symptoms of Schizophrenia as Measured on the PANSS
Hide Description

Positive and Negative Symptom Scale was used to assess psychopathology. The sum of items N1 - N7 including N1) blunted affect, N2) emotional withdrawal, N3) poor rapport, N4) passive apathetic social withdrawal, N5) difficulty in abstract thinking, N6) lack of spontaneity and flow of conversation, and N7) sterotyped thinking were used to analyze negative symptoms of schizophrenia and were assessed for the previous week:

RATING SCALE

1: Absent 2: Minimal 3: Mild 4: Moderate 5: Moderate Severe 6: Severe 7: Extreme The higher the score the worse the symptoms. The lowest possible score is 7 and the highest possible score is 49 .

Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done with those who completed the 6 month treatment protocol.
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 22 19
Mean (Standard Deviation)
Unit of Measure: units on a scale
16.9  (4.9) 17.2  (5.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Change in Positive Symptoms (PANSS)
Hide Description

Positive and Negative Symptom Scale was used to assess psychopathology. The Positive symptom subscale of schizophrenia includes the sum of items P1 -P7 including P1) Delusions, P2) conceptual Disorganization, P3) Hallunicatory Behavior, P4) Excitement, P5) Grandiosity, P6) Suspiciousness and Persecution, and P7) Hostility and were assessed for the previous week:

RATING SCALE

1: Absent 2: Minimal 3: Mild 4: Moderate 5: Moderate Severe 6: Severe 7: Extreme The higher the score the worse the symptoms. The lowest possible score is 7 and the highest possible score is 49 .

Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done with participants who completed the 6 month treatment phase
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 22 19
Mean (Standard Deviation)
Unit of Measure: units on a scale
13.7  (7.8) 12.5  (4.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, 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]
3.Secondary Outcome
Title Global Assessment of Functioning (GAF)
Hide Description

Measure Description: Clinical Measure of Global level of Symptoms (Sx) and Functioning from 1 (Worst) to 100 (Best) in groups of 10:

100 - 91: Superior functioning 90 - 81: Absent or minimal Sx 80 - 71: If symptoms are present and expected 70 - 61:Some mild Sx 60 - 51: Moderate Sx 50 - 41: Serious Sx 40 - 31: Some impairment in reality testing or communication 30 - 21: Behavior is considerably influenced by delusions or hallucinations 20 - 11: Some danger of hurting self or others 10 - 1: Persistent danger of severely hurting self or others

Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 22 19
Mean (Standard Deviation)
Unit of Measure: units on a scale
52.2  (11.7) 53.8  (11.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
4.Secondary Outcome
Title Social and Occupational Functioning Assessment Scale (SOFAS)
Hide Description

Measure of social and occupational functioning using the Social and Occupational Functioning Assessment Scale Measure Description: Rating of Overall Social and Occupational Functioning on a scale of 1 (worst) to 100 (best) in groups of 10:

100-91: Superior functioning 90-81: Good functioning 80-71: Slight impairment 70-61: Some difficulty 60-51: Moderate difficulty 50-41: Serious impairment 40-31: Major impairment 30-21: Inability to function in almost all areas 20-11: Unable to function independently 10-1: Unable to function without harming self or others

Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 22 19
Mean (Standard Deviation)
Unit of Measure: units on a scale
54.6  (11.3) 54.8  (10.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title Change in Cognition and Working Memory (MATRICS) Speed of Processing
Hide Description The MATRICS is neurocognitive battery designed to assess cognition. Processing speed is a composite score including the following tests: Trail Making Test, BACS: Symbol Coding, Category Fluency: Animal Naming. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 20 16
Mean (Standard Deviation)
Unit of Measure: T- Scores
41.47  (11.45) 35.85  (14.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments Speed of Processing
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Change in Cognition and Working Memory (MATRICS) Working Memory
Hide Description The MATRICS is neurocognitive battery designed to assess cognition. Working Memory score is a composite score based on the following sub-test WMS-III Spatial Span and Letter-Number Span. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 20 16
Mean (Standard Deviation)
Unit of Measure: T- Scores
47.47  (9.61) 38.08  (17.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.270
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title Change in Cognition and Working Memory (MATRICS) Attention and Vigilance
Hide Description The MATRICS is neurocognitive battery designed to assess cognition. Sustained attention and Vigilance is a composite score based on the Continuous Performance Test -Identical Pairs. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 20 16
Mean (Standard Deviation)
Unit of Measure: T- Scores
40.92  (12.98) 30.40  (13.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.153
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
8.Secondary Outcome
Title Change in Cognition and Working Memory (MATRICS) Verbal Learning
Hide Description The MATRICS is neurocognitive battery designed to assess cognition. Verbal Learning is a composite score based on the Hopkins Verbal Learning Test-Revised: Immediate Recall. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 20 16
Mean (Standard Deviation)
Unit of Measure: T- Scores
42.18  (10.36) 44.62  (12.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.876
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
9.Secondary Outcome
Title Change in Cognition and Working Memory (MATRICS) Visual Learning
Hide Description The MATRICS is neurocognitive battery designed to assess cognition. Visual Learning is a composite score based on the Brief Visuospatial Memory test - Revised: Immediate Recall. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 20 16
Mean (Standard Deviation)
Unit of Measure: T- Scores
46.00  (9.28) 47.75  (19.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.464
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
10.Secondary Outcome
Title Change in Cognition and Working Memory (MATRICS) Reasoning and Problem Solving
Hide Description The MATRICS is neurocognitive battery designed to assess cognition. Problem Solving is a composite score based on the NAB Mazes. The score is a standardized T-Score which indicates the number of standard deviations above or below the mean, a T-Score of 50, in 10 point increments. A T-Score of 60 indicates 1 standard deviation above the mean and a T-Score of 40 indicates 1 standard deviation below the mean. A score below 50 indicated cognitive processing below that of an age and gender matched healthy control population. A score above 50 indicates cognitive processing above that of an age and gender matched healthy control population.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of cognitive data is based on those who completed the cognitive testing at 6 months which required a separate clinic appointment and thus the overall number of participants is lower due to a loss of that data from failure to keep the cognitive testing appointment.
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 20 16
Mean (Standard Deviation)
Unit of Measure: T- Scores
51.13  (10.16) 44.38  (12.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.741
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
11.Secondary Outcome
Title Change in Blood Level of Glutathione
Hide Description Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids. The level of glutathione is measured in blood cells.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 22 19
Mean (Standard Deviation)
Unit of Measure: mM
0.92  (0.42) 0.82  (0.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, 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]
12.Secondary Outcome
Title Blood Plasma Level of Cysteine
Hide Description Cysteine is an amino acid, a building block for proteins and is used throughout the body and was measured in blood plasma.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 22 19
Mean (Standard Deviation)
Unit of Measure: uM
229.6  (62.9) 246.5  (42.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
13.Secondary Outcome
Title GPxbc Glutathione Peroxidase Activity in Blood Cells
Hide Description GPxBC is a measurement of glutathiione peroxidase enzymatic activity in glutathione synthesis and the redox system in blood cells. Measured as umol/min/gHb from blood cells.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 31 30
Mean (Standard Deviation)
Unit of Measure: umol/min/gHb
21.24  (7.5) 21.01  (6.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.90
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
14.Secondary Outcome
Title Glutamine Brain Level for NAC Group
Hide Description Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.
Arm/Group Title N-acetyl-cysteine
Hide Arm/Group Description:
n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: mM
3.16  (0.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6732
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
15.Secondary Outcome
Title Glutamine Brain Level for Placebo Group
Hide Description Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.
Arm/Group Title Placebo Group
Hide Arm/Group Description:

Placebo comparison group for study matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: mM
2.90  (0.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8786
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
16.Secondary Outcome
Title Glutamate Brain Level for NAC Group
Hide Description Brain marker, glutamate, was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutamate is an excitatory neurotransmitter in the brain.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.
Arm/Group Title N-acetyl-cysteine
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: mM
10.25  (1.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5622
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
17.Secondary Outcome
Title Glutamate Brain Level for Placebo Group
Hide Description Glutamine is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS) and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.
Arm/Group Title Placebo Group
Hide Arm/Group Description:
Placebo comparison group for study matching effervescent placebo tablets in water 2 in am and 1 in pm
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: mM
10.65  (1.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9574
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
18.Secondary Outcome
Title Glutathione Brain Level for NAC Group
Hide Description measured by H-MRS in the medial prefrontal cortex Brain markers, glutathione was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.
Arm/Group Title N-acetyl-cysteine
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: mM
1.04  (0.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0043
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
19.Secondary Outcome
Title Glutathione Brain Level for Placebo Group
Hide Description measured by H-MRS in the medial prefrontal cortex Brain markers, glutathione was measured using Magnetic Resonance Spectroscopy (H-MRS) in the medial prefrontal cortex. Glutathione is a tripeptide comprised of three amino acids (cysteine, glutamic acid, and glycine) and acts as an antioxidant, a free radical scavanger and a detoxifying agent. Glutathione is an important co-factor for the enzyme glutathione peroxidase used in the uptake of amino acids.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.
Arm/Group Title Placebo Group
Hide Arm/Group Description:
Placebo comparison group for study matching effervescent placebo tablets in water 2 in am and 1 in pm
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: mM
1.05  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3804
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
20.Secondary Outcome
Title Myo-Inositol Brain Level for the NAC Group
Hide Description Myo-Inositol is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS)MRS and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.
Arm/Group Title N-acetyl-cysteine
Hide Arm/Group Description:

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: mM
6.27  (1.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection N-acetyl-cysteine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9403
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
21.Secondary Outcome
Title Myo-Inositol Brain Level for Placebo Group
Hide Description Myo-Inositol is measured in the medial prefrontal cortex using Magnetic Resonance Spectroscopy (H-MRS)MRS and is a chemical that works to protect the brain from high levels of excitatory chemicals such as glutamate.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects in the NAC and Placebo group is lower as not everyone in the study agreed to a MRS, in addition the MRS was only done at the Switzerland site.
Arm/Group Title Placebo Group
Hide Arm/Group Description:
Placebo comparison group for study matching effervescent placebo tablets in water 2 in am and 1 in pm
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: mM
6.26  (1.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9215
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame Baseline and 6 months
Adverse Event Reporting Description Adverse Events were evaluated every month for 6 months and 1 month post treatment
 
Arm/Group Title N-acetyl-cysteine Placebo
Hide Arm/Group Description

N-Acetyl cysteine effervescent tablets in water 2 in am and 1 in pm for 28 weeks

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

matching effervescent tablets in water 2 in am and 1 in pm

n-acetylcysteine: 900 mg effervescent PharmaNAC tablet in water or juice: two tablets in the AM, one tablet in PM

All-Cause Mortality
N-acetyl-cysteine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/31 (0.00%)   0/30 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
N-acetyl-cysteine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/31 (0.00%)   0/30 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
N-acetyl-cysteine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   26/31 (83.87%)   29/30 (96.67%) 
Cardiac disorders     
Hypotension   7/31 (22.58%)  8/30 (26.67%) 
Hypertension   6/31 (19.35%)  5/30 (16.67%) 
Gastrointestinal disorders     
Nausea   10/31 (32.26%)  11/30 (36.67%) 
Constipation   11/31 (35.48%)  12/30 (40.00%) 
Immune system disorders     
Rash   6/31 (19.35%)  8/30 (26.67%) 
Nervous system disorders     
Tremor   11/31 (35.48%)  11/30 (36.67%) 
Rigidity   7/31 (22.58%)  13/30 (43.33%) 
Akathisia   11/31 (35.48%)  9/30 (30.00%) 
Dry Mouth   16/31 (51.61%)  15/30 (50.00%) 
Increased Salivation   7/31 (22.58%)  6/30 (20.00%) 
Sedation   18/31 (58.06%)  21/30 (70.00%) 
Psychiatric disorders     
Emotional Indifference   17/31 (54.84%)  21/30 (70.00%) 
Skin and subcutaneous tissue disorders     
Hair Loss   4/31 (12.90%)  4/30 (13.33%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Larry Seidman, PhD
Organization: Beth Israel Deaconess Medical Center
Phone: 617 754-1238
Responsible Party: Larry Seidman, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01354132     History of Changes
Other Study ID Numbers: 2008P000460
107865 ( Other Identifier: FDA IND )
First Submitted: May 13, 2011
First Posted: May 16, 2011
Results First Submitted: March 17, 2017
Results First Posted: June 7, 2017
Last Update Posted: July 5, 2017