A Randomized, Double-blind, Placebo-controlled Multicenter Study to Assess Efficacy and Safety of Pregabalin in Willis-Ekbom Disease/Restless Legs Syndrome
Overview
- Phase
- Phase 3
- Intervention
- Placebos
- Conditions
- Restless Legs Syndrome
- Sponsor
- Seoul National University Hospital
- Enrollment
- 116
- Locations
- 1
- Primary Endpoint
- International restless legs scale score
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This randomized, double-blind, placebo-controlled, multicenter clinical trial is designed to to assess the treatment efficacy and tolerability of pregabalin in patients with idiopathic restless legs syndrome in South Korea.
Detailed Description
Objectives: To assess the treatment efficacy and tolerability of pregabalin in patients with idiopathic restless legs syndrome (RLS) in South Korea. Study Design: A randomized, double-blind, placebo-controlled, multicenter clinical trial Study period: total 14 weeks: 2 weeks for placebo run in period and 12 weeks treatment after randomization (titration for 4 weeks and maintenance for 8 weeks). Subjects: a total number of 100 participants (randomly assigned 1:1 to pregabalin or placebo). The sample number was calculated based on a superiority design, 1-sided, alpha 0.05 with power 80% and drop rate 10%. Inclusion criteria: adults aged between 19-80 and diagnosed with idiopathic RLS with IRLS score of 15 or more. Exclusion criteria: Secondary RLS; serum ferritin \< 10 μg/L or history of oral iron therapy within 3 months or intravenous iron therapy within 1 year; severe comorbid medical or psychiatric disorders; history of pregabalin or gabapentin treatment within 3 months; other comorbid sleep disorders or shift workers. Treatment schedule and dose - Placebo responders, who showed a decrease of IRLS score of 40% or more, are excluded before randomization. Subjects will randomly assigned to receive either pregabalin or placebo with a 1:1 allocation. A starting dose is 75 mg/day for 2 weeks (taken 1-2 hours before habitual bedtime). At the visit of 2 weeks and 4 weeks, a dose can be titrated by 75-150 mg according to the response and tolerability. A dose ranging 75-300 mg per day will be maintained for 8 weeks. Primary outcome: changes in IRLS score after 12-week treatment. Secondary outcomes: remission rate (decrease in IRLS score of 50% or more), CGI (clinical global impression)-improvement, changes in 10-cm visual analog scale (VAS), RLS-6, PSQI (pittsburgh sleep quality index), ISI (insomnia severity index), Johns Hopkins RLS QoL after 12-week treatment. Statistical analysis: ANCOVA for changes in IRLS score with a baseline IRLS score as a covariate. Tolerability: Safety profiles and Liverpool Adverse Event Profile (LAEP) will be assessed.
Investigators
Ki-Young Jung
Professor
Seoul National University Hospital
Eligibility Criteria
Inclusion Criteria
- •IRLS (international restless legs scale) score ≥ 15
- •RLS symptom occurring ≥ 3 times/week and persisting over ≥ 6 months
- •Drug-naive patients or those who stop taking RLS drugs for ≥ 1 week before screening
Exclusion Criteria
- •Secondary RLS (including iron deficiency anemia, pregnancy, chronic kidney disease \[eGFR \< 60 mL/min/1.73 m2\], peripheral neuropathy, others)
- •Serum Ferritin \< 10 μg/L or history of oral iron therapy within 3 months or intravenous iron therapy within 1 year
- •Severe comorbid medical or psychiatric disorders
- •history of pregabalin or gabapentin treatment within 3 months
- •High risk of obstructive sleep apnea by STOP-BANG questionnaire
- •Other comorbid sleep disorders or shift workers
- •Hypersensitivity to pregabalin
- •Galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
Arms & Interventions
Placebo
Intervention: Placebos
Pregabalin
Intervention: Pregabalin 75mg
Outcomes
Primary Outcomes
International restless legs scale score
Time Frame: Baseline (week 0) and post-treatment (week 12)
Changes in International restless legs scale (IRLS) score after 12-week treatment. IRLS is used to assess the severity of patient's RLS symptoms. A total score ranges from 0 to 40 and higher scores mean more severe symptoms. Therefore, greater differences in IRLS scores between baseline and post-treatment mean a better outcome.
Secondary Outcomes
- Restless legs syndrome (RLS)-6(Baseline (week 0) and post-treatment (week 12))
- Johns Hopkins Restless legs syndrome quality of life(Baseline (week 0) and post-treatment (week 12))
- Remission rate(Baseline (week 0) and post-treatment (week 12))
- PSQI (pittsburgh sleep quality index)(Baseline (week 0) and post-treatment (week 12))
- 10-cm visual analog scale (VAS)(Baseline (week 0) and post-treatment (week 12))
- ISI (insomnia severity index)(Baseline (week 0) and post-treatment (week 12))
- CGI (clinical global impression)-improvement(Post-treatment (week 12))