RCT for Pregabalin in Restless Legs Syndrome in South Korea

Restless Legs Syndrome Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Multicenter Study to Assess Efficacy and Safety of Pregabalin in Willis-Ekbom Disease/Restless Legs Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04161027
• Other study ID #: 1903-121-1021
• Status: Completed
• Phase: Phase 3
• Start date: February 24, 2020
• Est. completion date: April 4, 2022

Study information

• Verified date: April 2023
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: April 4, 2022
• Est. primary completion date: April 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Psychomotor Agitation
• Restless Legs Syndrome
• Syndrome

Intervention

Drug:
• Pregabalin 75mg
Pregabalin 75 mg capsule
• Placebos
Placebo capsule

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	International restless legs scale score	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.	Baseline (week 0) and post-treatment (week 12)
Secondary	Remission rate	A proportion of patients who showed a decrease in IRLS score of 50% or more after treatment. Higher scores mean a better outcome.	Baseline (week 0) and post-treatment (week 12)
Secondary	CGI (clinical global impression)-improvement	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).	Post-treatment (week 12)
Secondary	10-cm visual analog scale (VAS)	Changes in 10-cm VAS after 12-week treatment. A VAS score ranges from 0 (no symptoms) to 10 (very severe symptoms).	Baseline (week 0) and post-treatment (week 12)
Secondary	Restless legs syndrome (RLS)-6	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).	Baseline (week 0) and post-treatment (week 12)
Secondary	PSQI (pittsburgh sleep quality index)	Changes in PSQI scores after 12-week treatment. A total PSQI score ranges from 0 to 21, and higher scores indicate worse sleep quality.	Baseline (week 0) and post-treatment (week 12)
Secondary	ISI (insomnia severity index)	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)	Baseline (week 0) and post-treatment (week 12)
Secondary	Johns Hopkins Restless legs syndrome quality of life	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.	Baseline (week 0) and post-treatment (week 12)