Restless Legs Syndrome
Conditions
Keywords
Restless legs syndrome; pregabalin; Willis-Ekbom disease
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.
Interventions
DRUGPregabalin 75mg
Pregabalin 75 mg capsule
DRUGPlacebos
Placebo capsule
Sponsors
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
A randomized, double-blind, placebo-controlled, multicenter clinical trial. Study subjects will be recruited from 4 medical centers in South Korea.
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| International restless legs scale score | 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
| Measure | Time frame | Description |
|---|---|---|
| CGI (clinical global impression)-improvement | Post-treatment (week 12) | The amount of RLS symptom improvement measured by physicians. CGI-improvement is a 7-point scale and rated as 1 (Very much improved), 2 (Much improved), 3 (Minimally improved), 4 (No change), 5 (Minimally worse), 6 (Much worse), and 7 (Very much worse). |
| 10-cm visual analog scale (VAS) | Baseline (week 0) and post-treatment (week 12) | Changes in 10-cm VAS after 12-week treatment. A VAS score ranges from 0 (no symptoms) to 10 (very severe symptoms). |
| Restless legs syndrome (RLS)-6 | Baseline (week 0) and post-treatment (week 12) | Changes in RLS-6 scores after 12-week treatment. A RLS-6 consists of 6 questions for RLS symptoms and a total score ranges from 0 (no symptoms) to 60 (very severe symptoms). |
| Remission rate | Baseline (week 0) and post-treatment (week 12) | A proportion of patients who showed a decrease in IRLS score of 50% or more after treatment. Higher scores mean a better outcome. |
| ISI (insomnia severity index) | Baseline (week 0) and post-treatment (week 12) | Changes in ISI scores after 12-week treatment. A total ISI score range from 0 to 28 and categories: 0-7 (No clinically significant insomnia), 8-14 (Subthreshold insomnia), 15-21 (Moderate insomnia), and 22-28 (Severe insomnia) |
| Johns Hopkins Restless legs syndrome quality of life | Baseline (week 0) and post-treatment (week 12) | Changes in Johns Hopkins Restless legs syndrome quality of life scores after 12-week treatment. A total score ranges from 0 to 100 and lower scores indicate worse quality of life. |
| PSQI (pittsburgh sleep quality index) | Baseline (week 0) and post-treatment (week 12) | Changes in PSQI scores after 12-week treatment. A total PSQI score ranges from 0 to 21, and higher scores indicate worse sleep quality. |
Countries
South Korea
Outcome results
None listed