Trial Outcomes & Findings for The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia (NCT NCT01234675)

NCT ID: NCT01234675

Last Updated: 2019-08-21

Results Overview

Number of awakenings after defined sleep onset until lights on.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 19 participants
• Primary outcome timeframe: 4-Week maintenance treatment with milnacipran and placebo
• Results posted on: 2019-08-21

Participant Flow

Participant milestones

Measure	Placebo Then Milnacipran 50 mg twice daily (BID) maintenance dose	Milnacipran Then Placebo 50 mg twice daily (BID) maintenance dose
First Intervention (6 Weeks) STARTED	10	9
First Intervention (6 Weeks) COMPLETED	9	8
First Intervention (6 Weeks) NOT COMPLETED	1	1
Second Intervention (6 Weeks) STARTED	9	8
Second Intervention (6 Weeks) COMPLETED	7	8
Second Intervention (6 Weeks) NOT COMPLETED	2	0

Reasons for withdrawal

Measure	Placebo Then Milnacipran 50 mg twice daily (BID) maintenance dose	Milnacipran Then Placebo 50 mg twice daily (BID) maintenance dose
First Intervention (6 Weeks) Adverse Event	0	1
First Intervention (6 Weeks) Withdrawal by Subject	1	0

Baseline Characteristics

The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia

Baseline characteristics by cohort

Measure	All Study Participants n=19 Participants 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
Age, Continuous	49.2 years n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Baseline polysomnographic sleep parameters Latency to persistent sleep (LPS)	49.4 minutes STANDARD_DEVIATION 43.4 • n=5 Participants
Baseline polysomnographic sleep parameters Total sleep time (TST)	340.7 minutes STANDARD_DEVIATION 78.9 • n=5 Participants
Baseline polysomnographic sleep parameters Wake after sleep onset (WASO)	97.2 minutes STANDARD_DEVIATION 70.6 • n=5 Participants
Number of awakenings after sleep onset (NAASO)	31.9 awakenings STANDARD_DEVIATION 12.9 • n=5 Participants
Sleep efficiency (SE)	72.3 percentage of total sleep time STANDARD_DEVIATION 15.8 • n=5 Participants
Arousal index (AI)	24.8 arousals per hour STANDARD_DEVIATION 9.8 • n=5 Participants
Total stage shifts	147.4 Stage shifts STANDARD_DEVIATION 42.2 • n=5 Participants
Rapid Eye Movement (REM) latency	126.5 minutes STANDARD_DEVIATION 91.3 • n=5 Participants
Sleep architecture Stage N1	18.9 percentage of total sleep time STANDARD_DEVIATION 6.6 • n=5 Participants
Sleep architecture Stage N2	59.0 percentage of total sleep time STANDARD_DEVIATION 13 • n=5 Participants
Sleep architecture Stage N3	4.2 percentage of total sleep time STANDARD_DEVIATION 8.4 • n=5 Participants
Sleep architecture REM Sleep	18.0 percentage of total sleep time STANDARD_DEVIATION 7.3 • n=5 Participants

PRIMARY outcome

Timeframe: 4-Week maintenance treatment with milnacipran and placebo

Population: 15 subjects completed the study

Number of awakenings after defined sleep onset until lights on.

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Number of Awakenings After Sleep Onset (NAASO)	39.5 Awakenings Standard Error 4.5	34.9 Awakenings Standard Error 4.2

PRIMARY outcome

Timeframe: 4-Week maintenance treatment with milnacipran and placebo

Percentage of time spent asleep while in bed

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Sleep Efficiency (SE)	77.1 percentage of total sleep time Standard Error 3.8	83.3 percentage of total sleep time Standard Error 2.3

PRIMARY outcome

Timeframe: 4-Week maintenance treatment with milnacipran and placebo

Wake time after defined sleep onset until lights on.

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Wake After Sleep Onset (WASO)	76.2 minutes Standard Error 10.8	53.6 minutes Standard Error 8.1

SECONDARY outcome

Timeframe: 4-Week treatment with milnacipran and placebo

It is defined as time from lights out to the first consecutive 2 minutes of uninterrupted sleep.

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Latency to Persistent Sleep Onset (LPS)	41.6 minutes Standard Error 6.2	38.6 minutes Standard Error 5.8

SECONDARY outcome

Timeframe: 4-Week treatment with milnacipran and placebo

Total sleep of all Rapid Eye Movement (REM) and Non- Rapid Eye Movement Sleep (NTREM) from lights out to lights on.

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Total Sleep Time (TST)	361.7 minutes Standard Error 19.6	386.1 minutes Standard Error 12.5

SECONDARY outcome

Timeframe: 4-Week treatment with milnacipran and placebo

Number of arousals per hour of sleep

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Arousal Index (AI)	30.2 arousals per hour Standard Error 2.2	31.2 arousals per hour Standard Error 4.0

SECONDARY outcome

Timeframe: 4-Week treatment with milnacipran and placebo

Time spent in stage 3 of non-rapid eye movement sleep and often referred to as deep sleep.

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Slow Wave Sleep (SWS)	8.4 percentage of total sleep time Standard Error 2.7	9.4 percentage of total sleep time Standard Error 2.6

SECONDARY outcome

Timeframe: 4-Week treatment with milnacipran and placebo

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.

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Sleep Problem Index 2, Medical Outcomes Study Sleep Scale (MOS-SS)	37.8 score on a scale Standard Error 4.4	34.9 score on a scale Standard Error 3.8

SECONDARY outcome

Timeframe: 4-Week treatment with milnacipran and placebo

Sleep quality measure derived from daily sleep diary rating ranging from 0 ("very poor") to 10 ("excellent")

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Sleep Quality Scale	5.2 score on a scale Standard Error 0.52	4.9 score on a scale Standard Error 0.4

SECONDARY outcome

Timeframe: 4-Week treatment with milnacipran and placebo

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.

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Fatigue Severity Scale (FSS) Total Score	41.0 score on a scale Standard Error 3.4	42.3 score on a scale Standard Error 3.1

SECONDARY outcome

Timeframe: 4-Week treatment with milnacipran and placebo

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.

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Fibromyalgia Impact Questionnaire (FIQ) Total Score	40.0 score on a scale Standard Error 6.8	45.3 score on a scale Standard Error 4.0

SECONDARY outcome

Timeframe: 4-Week treatment with milnacipran and placebo

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

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Brief Pain Inventory (BPI) Mean Severity Score	4.1 score on a scale Standard Error 0.6	4.7 score on a scale Standard Error 0.4

SECONDARY outcome

Timeframe: 4-Week treatment with milnacipran and placebo

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.

Outcome measures

Measure	Milnacipran n=15 Participants Treatment with 50 mg BiD	Placebo n=15 Participants 50 mg placebo BiD
Brief Pain Inventory (BPI) Mean Interference Score	3.8 score on a scale Standard Error 0.6	4.3 score on a scale Standard Error 0.5

Adverse Events

Milnacipran

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Milnacipran n=19 participants at risk Drug: milnacipran, 50 mg twice daily for 4 weeks.	Placebo n=19 participants at risk Drug: Placebo 50 mg, twice daily for 4 weeks.
Gastrointestinal disorders Gall Stones	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.

Other adverse events

Measure	Milnacipran n=19 participants at risk Drug: milnacipran, 50 mg twice daily for 4 weeks.	Placebo n=19 participants at risk Drug: Placebo 50 mg, twice daily for 4 weeks.
Gastrointestinal disorders nausea	21.1% 4/19 • Number of events 4 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Nervous system disorders Headache	15.8% 3/19 • Number of events 3 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
General disorders Dry Mouth	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Nervous system disorders Flushing	10.5% 2/19 • Number of events 2 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Gastrointestinal disorders Constipation	10.5% 2/19 • Number of events 2 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	10.5% 2/19 • Number of events 2 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Gastrointestinal disorders Abdominal pain	10.5% 2/19 • Number of events 2 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	15.8% 3/19 • Number of events 3 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Respiratory, thoracic and mediastinal disorders Sinusitis	10.5% 2/19 • Number of events 2 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Nervous system disorders Worsening of pain	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	10.5% 2/19 • Number of events 2 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
General disorders Increased Perspirations	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Respiratory, thoracic and mediastinal disorders cold/flu	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	10.5% 2/19 • Number of events 2 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Cardiac disorders Increased Heartrate	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Gastrointestinal disorders diarrhea	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Reproductive system and breast disorders Excessive menstrual bleeding	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Respiratory, thoracic and mediastinal disorders Streptococcal infection (throat)	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Renal and urinary disorders Excessive urination	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Skin and subcutaneous tissue disorders Periodontal disease	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Cardiac disorders Elevated Blood Pressure	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
General disorders Cold sweats	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Reproductive system and breast disorders Abnormal ejaculation	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Musculoskeletal and connective tissue disorders Foot sprain	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Immune system disorders Pruritis	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.
Immune system disorders Petechial rash	5.3% 1/19 • Number of events 1 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.	0.00% 0/19 • 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. Additional data was collected after the end of study visit if the patient reported an adverse event.

Additional Information

Mansoor Ahmed, MD

Cleveland Sleep Research Center

Phone: 4402438044

Email: sleepresearchcenter@yahoo.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place