Polysomnography Study Of Pregabalin And Pramipexole Versus Placebo In Patients With Restless Legs Syndrome And Associated Sleep Disturbance
This study has been completed.
Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00991276
First received: October 6, 2009
Last updated: September 6, 2012
Last verified: September 2012
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Purpose
The purpose of this study is to assess the efficacy and safety of pregabalin and pramipexole versus placebo in the treatment of restless legs syndrome and associated sleep disturbance.
Condition  Intervention  Phase 

Restless Legs Syndrome 
Drug: pregabalin Drug: placebo Drug: pramipexole 
Phase 3 
Study Type:  Interventional 
Study Design:  Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Participant, Investigator, Outcomes Assessor) Primary Purpose: Treatment 
Official Title:  A Randomized, DoubleBlind, PlaceboControlled, 3Way Crossover, Multicenter Polysomnography Study Of Pregabalin And Pramipexole In Adults With Restless Legs Syndrome 
Resource links provided by NLM:
Further study details as provided by Pfizer:
Primary Outcome Measures:
 Wake After Sleep Onset (WASO) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or Early Termination (ET) ]WASO as determined by Polysomnography (PSG) was time spent awake from sleep onset to final awakening. WASO= Wake Time During Sleep [WTDS] epochs + Wake Time After Sleep [WTAS] epochs)/2. WTDS: number of wake epochs (30 seconds of PSG recording) after onset of persistent sleep and prior to final awakening or end of 8hour recording/2 and WTAS: number of wake epochs after final awakening until end of the 8hour recording/2. WASO was measured on 2 consecutive days within a period. Arithmetic mean of WASO of each participant for all periods was taken prior to employing linear mixed model.
Secondary Outcome Measures:
 Periodic Limb Movement Arousal Index (PLMAI) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]PLMAI, as determined by PSG was number of periodic limb movements leading to arousal per hour (per hour of Total Sleep Time [TST]). Arithmetic mean of PLMAI of each participant for all periods was taken prior to employing linear mixed model.
 Subjective Total Sleep Time (sTST) [ Time Frame: Week 3 and Week 5 of Each Intervention Period or ET ]sTST as derived from Subjective Sleep Questionnaire (SSQ), a participant reported subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. Completed by the participant 30 minutes after waking; recall period is the night before. Arithmetic mean of sTST of each participant for all periods was taken prior to employing linear mixed model.
 Minutes of Stage N1, N2, N3 and R Sleep [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]Minutes of Stage 1 NonRapid Eye Movement (NonREM) sleep (Stage N1), Stage 2 NonREM sleep (Stage N2), Stage 3 NonREM sleep (Stage N3) or Slow Wave Sleep (SWS) and Stage REM (Stage R) sleep, as determined by PSG were calculated as total number of Stage N1 30second (30sec) epochs divided by 2, total number of Stage N2 30sec epochs divided by 2, total number of Stage N3 30sec epochs divided by 2 and total number of Stage R 30sec epochs divided by 2 respectively. Arithmetic mean of minutes of stage N1, N2, N3 and R sleep of each participant for all periods was taken prior to employing linear mixed model.
 Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]NAASO1, as determined by PSG, was the number of times there was a wake period of at least 1 epoch from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage 2 NonREM [Stage N2] 30second (30sec) epoch, Stage 3 NonREM [Stage N3] 30sec epoch, or stage rapid eye movement [stage R] 30sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NAASO1 of each participant for all periods was taken prior to employing linear mixed model.
 Restless Legs SyndromeNext Day Impact (RLSNDI) [ Time Frame: Week 3 and Week 5 of Each Intervention Period or ET ]RLSNDI:participantrated instrument to assess daytime performance and participant's previous night's sleep, consists of 14 items encompassing 5 domains:tiredness;emotional functioning;social functioning;cognitive functioning;activities of daily living and 1 global item for overall wellbeing. Each item: 010 scale; 0=Not at all; 10=Extremely. Total score: sum of scores from question 114 (question 10, 11: scores reversed). Total score range: 0140; higher scores: more severe impact. Arithmetic mean of RLSNDI of each participant for all periods was taken prior to employing linear mixed model.
 Periodic Limb Movement Index (PLMI) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]PLMI, as determined by PSG was number of periodic limb movements per hour based on time in bed (TIB). Arithmetic mean of PLMI of each participant for all periods was taken prior to employing linear mixed model.
 Periodic Limb Movement in Sleep Index (PLMSI) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]PLMSI, as determined by PSG was number of periodic limb movements in sleep per hour based on TST. Arithmetic mean of PLMSI of each participant for all periods was taken prior to employing linear mixed model.
 Number of Awakenings of at Least 2 Epochs After Sleep Onset (NAASO2) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]NAASO2, as determined by PSG, was the number of times there was a wake period of at least 2 30sec epochs from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30sec epoch, Stage N3 30sec epoch, or Stage R 30sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NAASO2 of each participant for all periods was taken prior to employing linear mixed model.
 Number of Arousals (NASO) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]NASO, as determined by PSG, was calculated as number of times there is a shift from a stage N2 to N3 or R 30sec epoch to a stage N1 30sec epoch from the onset of persistent sleep to light on. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period. Arithmetic mean of NASO of each participant for all periods was taken prior to employing linear mixed model.
 Arousal Index (NASOI) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]Arousal index, as determined by PSG, was NASO per hours of sleep from the onset of persistent sleep to light on. Arithmetic mean of NASOI of each participant for all periods was taken prior to employing linear mixed model.
 International Restless Legs Syndrome Study Group Rating Scale (IRLS) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]IRLS: psychometrically; clinically valid; clinicianadministered instrument assesses severity of RLS. RLS symptom severity and impact on daily living comprise of 10 items giving 2 subscale scores and 1 global score. Subscale scores: symptom severity(6 items) and impact on daily living(3 items), item 3 loaded equally on both subscales. Global score calculated from 10 items. Score of all items range from 04, total score range:040. Lower scores: lower severity and better quality of life. Arithmetic mean of IRLS of each participant for all periods was taken prior to employing linear mixed model.
 Percentage of Participants With Response to Clinical Global Impression  Improvement (CGII) Scale [ Time Frame: Baseline, Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]CGII: 7point clinician rated scale to assess improvement in disease condition as compared to the start of the study medication (baseline), ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved). Higher score = more affected.
 Latency to Stage R Sleep (LREM) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]LREM, as determined by PSG, was number of nonwake epochs from the beginning of the recording to the first occurrence of Stage R sleep divided by 2. Arithmetic mean of LREM of each participant for all periods was taken prior to employing linear mixed model.
 Latency to Persistent Sleep (LPS) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]LPS, as determined by PSG, was number of epochs from the beginning of the recording ("lightsout") to the start of the first 20 consecutive nonwake epochs (10 minutes of persistent sleep) divided by 2. Arithmetic mean of LPS of each participant for all periods was taken prior to employing linear mixed model.
 Wake Time During Sleep (WTDS) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]WTDS, as determined by PSG, was the number of wake (30sec) epochs after the onset of persistent sleep and prior to the final awakening or at the end of 8hour recording. WTDS was the sum of 2 consecutive days of recordings divided by 2 at the end of each intervention period. Arithmetic mean of WTDS of each participant for all periods was taken prior to employing linear mixed model.
 Wake Time After Sleep (WTAS) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]WTAS, as determined by PSG, was the number of wake (30sec) epochs after the final awakening until the end of the 8hour recording. WTAS was the sum of 2 consecutive days of recordings divided by 2 at the end of each intervention period. Arithmetic mean of WTAS of each participant for all periods was taken prior to employing linear mixed model.
 Total Sleep Time (TST) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]TST, as determined by PSG, was the number of nonwake (30sec) epochs from the beginning of recording to the end of the recording. TST was the sum of 2 consecutive days of recording divided by 2 at the end of each intervention period. Arithmetic mean of TST of each participant for all periods was taken prior to employing linear mixed model.
 Sleep Efficiency (SE) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]SE, as determined by PSG, was the TST divided by the time in bed (TIB)(both in minutes), multiplied by 100. Sum of 2 consecutive days of recording divided by 2 at the end of each intervention period. Arithmetic mean of SE of each participant for all periods was taken prior to employing linear mixed model.
 Hourly and Quarterly Assessment of Wake After Sleep Onset (WASO) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]WASO, as determined by PSG was time spent awake from sleep onset to final awakening. WASO = (sum of WTDS 30sec epochs and WTAS 30sec epochs)/2, measured on 2 consecutive days at end of each intervention period by each individual hour (8 hours total) and each individual quarter of night (eight hours in 2 hour increments). Arithmetic mean of WASO of each participant for all periods was taken prior to employing linear mixed model.
 Hourly and Quarterly Assessment of Number of Awakenings of at Least 1 Epoch After Sleep Onset (NAASO1) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]NAASO1, as determined by PSG, was the number of times there was a wake period of at least 1 30sec epoch from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30sec epoch, Stage N3 30sec epoch, or Stage R 30sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NAASO1 of each participant for all periods was taken prior to employing linear mixed model.
 Hourly and Quarterly Assessment of Number of Awakenings of at Least 2 Epoch After Sleep Onset (NAASO2) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]NAASO2, as determined by PSG, was the number of times there was a wake period of at least 2 30sec epochs from the onset of persistent sleep to light on. Each entry to be counted must be separated by a Stage N2 30sec epoch, Stage N3 30sec epoch, or Stage R 30sec epoch. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NAASO2 of each participant for all periods was taken prior to employing linear mixed model.
 Hourly and Quarterly Assessment of Number of Arousals (NASO) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]NASO, as determined by PSG was the number of times there is a shift from a stage N2 to N3 or R 30sec epoch to a stage N1 30sec epoch from the onset of persistent sleep to light on. The sum of 2 consecutive days of recording was divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of NASO for each participant at each period was taken prior to employing linear mixed model.
 Hourly and Quarterly Assessment of Periodic Limb Movement (PLM) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]PLM, as determined by PSG was number of periodic limb movements based on time in bed (TIB). Calculated at each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean of PLM of each participant for all periods was taken prior to employing linear mixed model.
 Hourly and Quarterly Assessment of Sleep Efficiency (SE) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]SE, as determined by PSG, was the TST divided by the time in bed (TIB)(both in minutes), multiplied by 100. Sum of 2 consecutive days of recording divided by 2 at the end of each intervention period by each individual hour (8 hours total) and each individual quarter of the night (eight hours in 2 hour increments). Arithmetic mean for SE of each participant for all periods was taken prior to employing linear mixed model.
 Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale [ Time Frame: Week 3 and Week 5 of Each Intervention Period or ET ]SSQ: participantrated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items giving 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This (1 item) subscale: numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0 awakenings to 30 awakenings. Lower value indicates better quality of sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST.
 Subjective Sleep Questionnaire (SSQ): Total Wake Time After Sleep Onset Subscale [ Time Frame: Week 3 and Week 5 of each intervention period or ET ]SSQ: participantrated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This 1 item subscale (in minutes): numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 01440 minutes. Lower value: better sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST.
 Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale [ Time Frame: Week 3 and Week 5 of each intervention period or ET ]SSQ: participantrated instrument to assess sleep behavior; measures sleep quantity, quality. Comprised of 5 items yielding 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. This 1 item subscale: numerical rating completed by participant 30 minutes after waking; recall period: night before, Range: 0 to 100, higher score: better quality of sleep. Arithmetic mean of this subscale score of each participant for all periods was taken prior to employing linear mixed model. Results of hours of sleep subscale reported as sTST.
 Subjective Sleep Questionnaire (SSQ): Latency Subscale [ Time Frame: Week 3 and Week 5 of each intervention period or ET ]SSQ: participantrated instrument assesses sleep behavior; measures sleep quantity, quality. Comprised of 5 items giving 5 subscale scores: latency, hours of sleep, number of awakenings, total wake time after sleep onset, quality of sleep. Latency (time to fall asleep [in minutes]): numerical rating completed by participant 30 minutes after waking; recall period: night before. Range: 0  840 minutes, lower value: better sleep. Arithmetic mean of subscale score of each participant for all periods was taken prior to employing linear mixed model. Hours of sleep subscale results reported as sTST.
 Medical Outcomes Study  Sleep Scale (MOSSS) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]MOSSS:Participant rated instrument, assesses sleep quantity, quality;with 12 items(7 subscale scores:sleep disturbance, snoring, awakening short of breath/with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep;2 composite index scores:sleep problems Index I, II). Subscale scores total range:0100(except sleep quantity[range 024 hours], optimal sleep[range 01: 0= <7 or >8 hours;1=7/8 hours]). Higher scores=poorer sleep outcomes(except sleep quantity, adequacy). Arithmetic mean of MOSSS scores of each participant for all periods was taken before linear mixed model analysis.
 Restless Leg Syndrome  Quality of Life Scale (RLSQoL) [ Time Frame: Week 5 (End of Intervention Period 1), Week 11 (End of Intervention Period 2) and Week 17 (End of Intervention Period 3) or ET ]RLSQoL: psychometrically and clinically valid and reliable participantrated instrument, assesses impact of RLS on participant quality of life. Specifically, it assessed effects of RLS on health status function (symptom severity, daily activity, social functioning, sleep, concentrating and decision making, travelling, sexual activity, and work) giving a summary score ranging from 0100. Higher scores reflect better quality of life. Recall period: 1 week prior to assessment. Arithmetic mean of RLSQoL score of each participant for all periods was taken prior to employing linear mixed model.
Enrollment:  85 
Study Start Date:  December 2009 
Study Completion Date:  June 2011 
Primary Completion Date:  June 2011 (Final data collection date for primary outcome measure) 
Arms  Assigned Interventions 

Experimental: pregabalin 
Drug: pregabalin
capsules; 300 mg onceperday; 4 weeks of treatment
Other Name: Lyrica

Placebo Comparator: placebo 
Drug: placebo
capsules; 0 mg onceperday; 4 weeks of treatment

Active Comparator: pramipexole 
Drug: pramipexole
capsules; 0.5 mg onceperday; 4 weeks of treatment
Other Name: Mirapex

Eligibility
Ages Eligible for Study:  18 Years and older (Adult, Senior) 
Sexes Eligible for Study:  All 
Accepts Healthy Volunteers:  No 
Criteria
Inclusion Criteria:
 Diagnosis of restless legs syndrome with a total score of 15 or more points on the International RLS rating scale (IRLS).
 RLS symptoms interfering with sleep on 3 or more nights per week for at least 6 months.
 PSG confirmation of WASO of at least 60 min, PLMI of 10 or more, and total sleep time of at least 3 hrs and less than 6.5 hrs.
Exclusion Criteria:
 Secondary RLS.
 Daytime RLS symptoms requiring treatment.
 Primary sleep disorder.
 Sleep apnea.
 Night or shift work.
 Concurrent medical disorder that could interfere with efficacy assessment or present a safety concern.
 Pregnant or lactating women.
 Women of childbearing potential not using acceptable method of birth control.
 Use of prohibited medication.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00991276
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00991276
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Sponsors and Collaborators
Pfizer
Investigators
Study Director:  Pfizer CT.gov Call Center  Pfizer 
More Information
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Keywords provided by Pfizer:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on April 24, 2017
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party:  Pfizer 
ClinicalTrials.gov Identifier:  NCT00991276 History of Changes 
Other Study ID Numbers: 
A0081185 
Study First Received:  October 6, 2009 
Results First Received:  May 18, 2012 
Last Updated:  September 6, 2012 
Keywords provided by Pfizer:
restless legs syndrome RLS polysomnography PSG sleep disturbance patient reported outcome 
Additional relevant MeSH terms:
Syndrome Psychomotor Agitation Restless Legs Syndrome Disease Pathologic Processes Dyskinesias Neurologic Manifestations Nervous System Diseases Psychomotor Disorders Neurobehavioral Manifestations Signs and Symptoms Sleep Disorders, Intrinsic Dyssomnias Sleep Wake Disorders Parasomnias 
Mental Disorders Pramipexole Pregabalin Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs Antiparkinson Agents AntiDyskinesia Agents Dopamine Agonists Dopamine Agents Neurotransmitter Agents Analgesics Sensory System Agents Peripheral Nervous System Agents 
ClinicalTrials.gov processed this record on April 24, 2017