Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 73 of 88 for:    "Neuromuscular Disease" | "Norepinephrine"

The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia

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: NCT01234675
Recruitment Status : Completed
First Posted : November 4, 2010
Results First Posted : July 22, 2015
Last Update Posted : August 21, 2019
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Mansoor Ahmed M.D., Cleveland Sleep Research Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Sleep Disorders
Fibromyalgia
Sleep
Interventions Drug: Milnacipran
Drug: Placebo
Enrollment 19
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Then Milnacipran Milnacipran Then Placebo
Hide Arm/Group Description 50 mg twice daily (BID) maintenance dose 50 mg twice daily (BID) maintenance dose
Period Title: First Intervention (6 Weeks)
Started 10 9
Completed 9 8
Not Completed 1 1
Reason Not Completed
Adverse Event             0             1
Withdrawal by Subject             1             0
Period Title: Second Intervention (6 Weeks)
Started 9 8
Completed 7 8
Not Completed 2 0
Arm/Group Title All Study Participants
Hide Arm/Group Description 2 treatment period, with each period 6 weeks and 7 day washout period Milnacipran in treatment period 1, Placebo in treatment period 2 Placebo treatment in Period 1, and Milnacipran in Period 2
Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 19 participants
49.2
(28 to 72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
17
  89.5%
Male
2
  10.5%
Baseline polysomnographic sleep parameters  
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 19 participants
Latency to persistent sleep (LPS) 49.4  (43.4)
Total sleep time (TST) 340.7  (78.9)
Wake after sleep onset (WASO) 97.2  (70.6)
Number of awakenings after sleep onset (NAASO)  
Mean (Standard Deviation)
Unit of measure:  Awakenings
Number Analyzed 19 participants
31.9  (12.9)
Sleep efficiency (SE)  
Mean (Standard Deviation)
Unit of measure:  Percentage of total sleep time
Number Analyzed 19 participants
72.3  (15.8)
Arousal index (AI)  
Mean (Standard Deviation)
Unit of measure:  Arousals per hour
Number Analyzed 19 participants
24.8  (9.8)
Total stage shifts   [1] 
Mean (Standard Deviation)
Unit of measure:  Stage shifts
Number Analyzed 19 participants
147.4  (42.2)
[1]
Measure Description: Sleep stage shifts: stage 1, stage 2, stage 3, REM sleep
Rapid Eye Movement (REM) latency   [1] 
Mean (Standard Deviation)
Unit of measure:  Minutes
Number Analyzed 19 participants
126.5  (91.3)
[1]
Measure Description: Time from sleep onset to the first epoch of rapid eye movement (REM) sleep
Sleep architecture   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of total sleep time
Number Analyzed 19 participants
Stage N1 18.9  (6.6)
Stage N2 59.0  (13)
Stage N3 4.2  (8.4)
REM Sleep 18.0  (7.3)
[1]
Measure Description: Pattern of sleep as it shifts between the different sleep stages. Sleep stages 1-3 are collectively referred to as non--rapid eye movement sleep (NREM)
1.Primary Outcome
Title Number of Awakenings After Sleep Onset (NAASO)
Hide Description Number of awakenings after defined sleep onset until lights on.
Time Frame 4-Week maintenance treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
15 subjects completed the study
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: Awakenings
39.5  (4.5) 34.9  (4.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.424
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value 4.6
Confidence Interval (2-Sided) 95%
-7.3 to 16.6
Estimation Comments [Not Specified]
2.Primary Outcome
Title Sleep Efficiency (SE)
Hide Description Percentage of time spent asleep while in bed
Time Frame 4-Week maintenance treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: percentage of total sleep time
77.1  (3.8) 83.3  (2.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.049
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value -6.1
Confidence Interval (2-Sided) 95%
-12.2 to -0.04
Estimation Comments [Not Specified]
3.Primary Outcome
Title Wake After Sleep Onset (WASO)
Hide Description Wake time after defined sleep onset until lights on.
Time Frame 4-Week maintenance treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: minutes
76.2  (10.8) 53.6  (8.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.056
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value 22.6
Confidence Interval (2-Sided) 95%
-0.6 to 45.8
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Latency to Persistent Sleep Onset (LPS)
Hide Description It is defined as time from lights out to the first consecutive 2 minutes of uninterrupted sleep.
Time Frame 4-Week treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: minutes
41.6  (6.2) 38.6  (5.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.683
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value -6.1
Confidence Interval (2-Sided) 95%
-12.5 to 18.5
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Total Sleep Time (TST)
Hide Description Total sleep of all Rapid Eye Movement (REM) and Non- Rapid Eye Movement Sleep (NTREM) from lights out to lights on.
Time Frame 4-Week treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: minutes
361.7  (19.6) 386.1  (12.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.155
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value -1.502
Confidence Interval (2-Sided) 95%
-59.1 to 10.4
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Arousal Index (AI)
Hide Description Number of arousals per hour of sleep
Time Frame 4-Week treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: arousals per hour
30.2  (2.2) 31.2  (4.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.805
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-9.8 to 7.8
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Slow Wave Sleep (SWS)
Hide Description Time spent in stage 3 of non-rapid eye movement sleep and often referred to as deep sleep.
Time Frame 4-Week treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: percentage of total sleep time
8.4  (2.7) 9.4  (2.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.844
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-11.6 to 9.6
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Sleep Problem Index 2, Medical Outcomes Study Sleep Scale (MOS-SS)
Hide Description This is a subjective index derived from the medical outcomes study sleep scale (MOS-SS) scored on a 0-100 possible range with higher scores indicating more severe sleep disruption. The scale is a self-report instrument consisting of 12 items that assess perceived initiation and maintenance of sleep, respiratory problems during sleep, sleep duration, perceived adequacy of sleep and daytime somnolence.
Time Frame 4-Week treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: score on a scale
37.8  (4.4) 34.9  (3.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.509
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
-6.4 to 12.2
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Sleep Quality Scale
Hide Description Sleep quality measure derived from daily sleep diary rating ranging from 0 ("very poor") to 10 ("excellent")
Time Frame 4-Week treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: score on a scale
5.2  (0.52) 4.9  (0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
-0.3 to 0.6
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Fatigue Severity Scale (FSS) Total Score
Hide Description The scale is a 9-item self-report of fatigue in the past week and scored on a 7-point scale with 1 = strongly disagree and 7 = strongly agree. Scores range from 9 to 63 with higher scores indicating higher fatigue severity. A total score greater or equal to 36 suggests fatigue.
Time Frame 4-Week treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: score on a scale
41.0  (3.4) 42.3  (3.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.685
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value -1.03
Confidence Interval (2-Sided) 95%
-8.2 to 5.6
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Fibromyalgia Impact Questionnaire (FIQ) Total Score
Hide Description The scale is composed of 10 items relating to fibromyalgia symptoms experienced in the past week. Score ranges from 0 to 100 with higher scores indicating a greater effect of fibromyalgia on a person's life.
Time Frame 4-Week treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: score on a scale
40.0  (6.8) 45.3  (4.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.349
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value -5.3
Confidence Interval (2-Sided) 95%
-17.0 to 6.4
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Brief Pain Inventory (BPI) Mean Severity Score
Hide Description The score is derived from the BPI scale and measures pain intensity in the past 24 hour. The pain severity score is derived as the average score of 4 pain items assessing pain at its "worst", "least", "average" and "now" and ranges from 0-10 with higher scores reflecting greater pain
Time Frame 4-Week treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: score on a scale
4.1  (0.6) 4.7  (0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.305
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.8 to 5.6
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Brief Pain Inventory (BPI) Mean Interference Score
Hide Description The score is derived from the BPI scale and measures the effect of pain on functioning in the past 24 hour. It is the average score of 7 items interfering with general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. Score ranges from 0-10 with higher scores reflecting greater interference.
Time Frame 4-Week treatment with milnacipran and placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:
Treatment with 50 mg BiD
50 mg placebo BiD
Overall Number of Participants Analyzed 15 15
Mean (Standard Error)
Unit of Measure: score on a scale
3.8  (0.6) 4.3  (0.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Milnacipran, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.425
Comments [Not Specified]
Method Paired T test
Comments [Not Specified]
Method of Estimation Estimation Parameter Paired difference
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.8 to 0.8
Estimation Comments [Not Specified]
Time Frame Adverse event data was collected on and after Day 1 of the first treatment period. The data collection continued till the two weeks after the second treatment period.
Adverse Event Reporting Description Additional data was collected after the end of study visit if the patient reported an adverse event.
 
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description Drug: milnacipran, 50 mg twice daily for 4 weeks. Drug: Placebo 50 mg, twice daily for 4 weeks.
All-Cause Mortality
Milnacipran Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Milnacipran Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/19 (0.00%)      1/19 (5.26%)    
Gastrointestinal disorders     
Gall Stones  [1]  0/19 (0.00%)  0 1/19 (5.26%)  1
Indicates events were collected by systematic assessment
[1]
During the study the subject was diagnosed with having gall stones. After the blind was broken, the site found out that she was on placebo, and was never treated with the study drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Milnacipran Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/19 (63.16%)      10/19 (52.63%)    
Cardiac disorders     
Increased Heartrate   1/19 (5.26%)  1 0/19 (0.00%)  0
Elevated Blood Pressure   0/19 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal disorders     
nausea  [1]  4/19 (21.05%)  4 0/19 (0.00%)  0
Constipation   2/19 (10.53%)  2 2/19 (10.53%)  2
Abdominal pain   2/19 (10.53%)  2 3/19 (15.79%)  3
diarrhea   0/19 (0.00%)  0 1/19 (5.26%)  1
General disorders     
Dry Mouth   1/19 (5.26%)  1 1/19 (5.26%)  1
Increased Perspirations   1/19 (5.26%)  1 0/19 (0.00%)  0
Cold sweats   1/19 (5.26%)  1 0/19 (0.00%)  0
Immune system disorders     
Pruritis   1/19 (5.26%)  1 0/19 (0.00%)  0
Petechial rash   1/19 (5.26%)  1 0/19 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Foot sprain   1/19 (5.26%)  1 0/19 (0.00%)  0
Nervous system disorders     
Headache   3/19 (15.79%)  3 0/19 (0.00%) 
Flushing   2/19 (10.53%)  2 0/19 (0.00%)  0
Worsening of pain   0/19 (0.00%)  0 2/19 (10.53%)  2
Renal and urinary disorders     
Excessive urination   1/19 (5.26%)  1 0/19 (0.00%)  0
Reproductive system and breast disorders     
Excessive menstrual bleeding   1/19 (5.26%)  1 0/19 (0.00%)  0
Abnormal ejaculation   1/19 (5.26%)  1 0/19 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Sinusitis   2/19 (10.53%)  2 1/19 (5.26%)  1
cold/flu   1/19 (5.26%)  1 2/19 (10.53%)  2
Streptococcal infection (throat)   0/19 (0.00%)  0 1/19 (5.26%)  1
Skin and subcutaneous tissue disorders     
Periodontal disease   1/19 (5.26%)  1 0/19 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
nausea and vomiting
A well-established adaptation and re-adaptation to laboratory effects may have compromised our results. Other study biases include biases inherent in the crossover design, and a small sample size.
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
Layout table for Results Point of Contact information
Name/Title: Mansoor Ahmed, MD
Organization: Cleveland Sleep Research Center
Phone: 4402438044
EMail: sleepresearchcenter@yahoo.com
Layout table for additonal information
Responsible Party: Mansoor Ahmed M.D., Cleveland Sleep Research Center
ClinicalTrials.gov Identifier: NCT01234675     History of Changes
Other Study ID Numbers: SAV-MD-17
First Submitted: November 3, 2010
First Posted: November 4, 2010
Results First Submitted: February 5, 2015
Results First Posted: July 22, 2015
Last Update Posted: August 21, 2019