RCT for Pregabalin in Restless Legs Syndrome in South Korea

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

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.

Study Overview

• Status: Completed
• Conditions: Restless Legs Syndrome
• Intervention / Treatment: Drug: Pregabalin 75mg; Drug: Placebos

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.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebos; Placebo capsule
Experimental: Pregabalin	Drug: Pregabalin 75mg; Pregabalin 75 mg capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Ki-Young Jung, MD, PhD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Actual): April 4, 2022
• Study Completion (Actual): April 4, 2022

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 10, 2019
• First Posted (Actual): November 13, 2019

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Restless legs syndrome; pregabalin; Willis-Ekbom disease
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Dyskinesias; Psychomotor Disorders; Parasomnias; Syndrome; Psychomotor Agitation; Restless Legs Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: 1903-121-1021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No