Effects Of Pregabalin (Lyrica) On Sleep Maintenance In Subjects With Fibromyalgia

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate the effect of Lyrica on Wake after sleep onset in subjects with fibromyalgia with sleep maintenance disturbance (on polysomnogram)

Official Title
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Effects Of Pregabalin On Sleep Maintenance In Subjects With Fibromyalgia Syndrome And Sleep Maintenance Disturbance: A Randomized Placebo-Controlled 2-Way Crossover Polysomnography Study

Conditions
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Fibromyalgia, Sleep Disorders

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet diagnostic criteria for fibromyalgia; Subjects must report difficulty in maintaining sleep at least 3 times per week and meet Research Diagnostic Criteria (RDC) for insomnia disorder, corroborated by subject diary, and meet PSG inclusion criteria at visit 3. Exclusion Criteria: History of active sleep disorder other than Research Diagnostic Criteria(RDC) insomnia criteria or any sleep or circadian rhythm disturbance; Use of medications known to affect sleep wake function by Visit 2; Involved in night or rotating shift work, or travel across >4 time zones 14 days prior to screening and during study; regular daytime napping PSG finding of apnea/hypopnea or periodic limb movement with arousal index >10/hr on either night of PSG.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lyrica<br>flexible dosing Lyrica 300-450mg/day | Drug: Pregabalin<br>* Capsule, flexible dosing double-blind. Treatment duration is approximately 4 weeks titrated to 300-450 mg/day<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Capsule, flexible dosing double-blind. Treatment duration is approximately 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wake After Sleep Onset (WASO) at Weeks 5 and 11 | WASO was the sum of wake time during sleep measured in epochs (30 seconds of polysomnography [PSG]) recording) after the onset of persistent sleep and prior to final awakening and wake time after sleep (the number of epochs after the final awakening until the end of PSG recording [i.e. awake epoch immediately prior to the end of the recording]) on 2 consecutive nights divided by 2 at the end of each intervention period. | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or Early Termination (ET) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wake Time During Sleep (WTDS) | WTDS, as determined by PSG, was the total amount of time awake the participant experienced after the onset of persistent sleep and prior to the final awakening, or at the end of 8 hours of recording. WTDS was the sum of 2 consecutive nights of recordings divided by 2 at the end of each intervention period. | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | 
| Wake Time After Sleep (WTAS) | WTAS, as determined by PSG, was the total amount of time awake after the final awakening until the end of the 8 hours. WTAS was the sum of 2 consecutive nights of recordings divided by 2 at the end of each intervention period. | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | 
| Total Sleep Time (TST) | TST, as determined by PSG, was the number of non-wake epochs from the beginning of recording to the end of the recording. TST was the sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period. | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | 
| Sleep Efficiency (SE) | SE, as determined by PSG, was the TST divided by the time in bed, multiplied by 100. The sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period. | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | 
| Number of Awakenings After Sleep Onset (NAASO 1) | NAASO 1, as determined by PSG, was the number of times there was a wake period of at least one epoch in duration. Each entry counted was separated by a Stage 2 epoch, Stage 3 and 4 epoch, or Stage rapid eye movement (REM) epoch. The sum of 2 consecutive nights of recording was divided by 2 at the end of each intervention period. | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | 
| Number of Awakenings After Sleep Onset (NAASO 2) | NAASO 2, as determined by PSG, was the number of times that there was a wake period of at least two epochs in duration. Each entry counted was separated by a Stage 2 epoch, Stage 3 and 4 epoch, or Stage REM epoch. The sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period. | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | 
| Latency to Persistent Sleep (LPS) | LPS, as determined by PSG, was the total number of epochs recorded on 2 consecutive nights divided by 2 at the end of each intervention period, from the beginning of the recording to the start of the first 20 consecutive non-wake epochs. | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | 
| WASO by Hour of the Night | WASO, as determined by PSG, was the wake time during sleep (number of wake epochs after the onset of persistent sleep and prior to final awakening) and wake time after sleep (the number of epochs after the final awakening until the end of PSG recording) on 2 consecutive nights divided by 2 at the end of each intervention period by each individual hour (8 hours total). | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | 
| WASO by Each Quarter of the Night | WASO, as determined by PSG, was the sum of wake time during sleep (number of wake epochs after the onset of persistent sleep and prior to final awakening) and wake time after sleep (the number of epochs after the final awakening until the end of PSG recording) on 2 consecutive nights divided by 2 at the end of each intervention period by each individual quarter of the night (eight hours in 2 hour increments). | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | 
| Slow Wave Sleep (SWS) | SWS, as determined by PSG, Stage 3 plus 4 sleep divided by TST times 100 was the percentage of TST. The sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period. | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | 
| Change From Baseline in MOS-SS Sleep Disturbance at Weeks 5 and 11 | MOS-SS, a participant rated instrument used to assess sleep quantity and quality over the previous week, was comprised of 12 items yielding 7 subscale scores and 2 index composite index scores. Sleep Disturbance subscale score (4 items): individual scores were transformed (actual raw score minus lowest possible score divided by possible raw score range times 100) and ranged from 0 to 100; higher score indicated greater disturbance. Total score ranged=0 to 100; higher score indicates greater intensity of attribute. Change was score at week x minus score at baseline. | Week 1 (Baseline Intervention Period 1), Week 5 (End of Intervention Period 1), Week 7 (Baseline Intervention Period 2) and Week 11 (End of Intervention Period 2) or ET | 
| Change From Baseline in MOS-SS Sleep Problems Index II Weeks 5 and 11 | MOS-SS, a participant rated instrument used to assess sleep quantity and quality over the previous week, was compromised of 12 items yielding 7 subscale scores and 2 index composite index scores. Composite index included Sleep Problems Index II (9 items), scores ranged from 0 to 100; higher scores indicated greater sleep problems. Change was score at week x minus score at baseline. | Week 1 (Baseline Intervention Period 1), Week 5 (End of Intervention Period 1), Week 7 (Baseline Intervention Period 2) and Week 11 (End of Intervention Period 2) or ET | 
| Sleep Quality | Sleep Quality as meassured by numeric rating scale (NRS), a participant rated scale 0 to 10, (0 = very poor sleep, 10 = excellent sleep). Weekly values were calculated as the average of the participants daily diary scores. | Weeks 1, 2, 3 and 4 of Each Intervention Period or ET | 
| Latency of Sleep Onset (LSO) | LSO as reported on daily Subjective Sleep Questionnaire (SSQ), a participant reported subjective estimate of the amount of time to fall asleep after lights out. Weekly values were calculated as the average minutes reported on the participant's daily SSQ. | Weeks 1, 2, 3 and 4 of Each Intervention Period or ET | 
| Daily Pain Score | Pain intensity as measured by NRS; a participant rated scale 0 to 10 (0 = no pain to 10 = worst pain possible). Weekly values were calculated as the average of the participants daily pain scores. | Daily up to Day 73 or ET | 
| Subjective Wake After Sleep Onset (sWASO) | sWASO as reported on daily SSQ, a participant reported subjective estimate of the total amount of time the participant was awake after initial sleep onset until final awakening. Weekly values were calculated as the average of the participant's daily SSQ values. | Weeks 1, 2, 3 and 4 of Each Intervention Period or ET | 
| Subjective Total Sleep Time (sTST) | sTST as reported on daily SSQ, a participant reported subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. Weekly values were calculated as the average of the participants daily SSQ values. | Weeks 1, 2, 3 and 4 of Each Intervention Period or ET | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibromyalgia sleep maintenance disturbance pregabalin