Efficacy and Safety Study of Topiramate to Treat Restless Legs Syndrome

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Determine the Effacy and Safety of Topiramate in Subjects With Restless Legs Syndrome (RLS)

This study is intended to determine whether topiramate is an efficacious and safe treatment for restless legs syndrome.

Study Overview

• Status: Completed
• Conditions: Restless Legs Syndrome
• Intervention / Treatment: Drug: Topiramate

Detailed Description

Benzodiazepines, levo-dopa/carbidopa, dopamine agonists, anticonvulsants, and opioids have been used with variable success, to treat RLS. Often, RLS patients treated with a benzodiazepine, over the course of several months, develop tolerance to the medication. Also, benzodiazepines can cause confusion or daytime sleepiness and may be addictive. Patients may also develop tolerance to levo-dopa/carbidopa treatment. Because of the short half-life, symptoms may be suppressed for only the first part of the sleep period and then recur later during the night. Rebound has been reported. Worse yet, augmentation, the occurrence of RLS symptoms, often more severe than before treatment began, earlier in the day, may occur in up to 80% of RLS patients treated with levod-dopa/carbidopa. Dopamine agonists, including pergolide, pramipexole, and ropinirole, are effective for some patients but not for others. Common side effects of these drugs include coryza, hypotension, and rash. Of the anticonvulsants, preliminary reports suggest that gabapentin, carbamazepine, and divalproex can suppress RLS symptoms in some patients, especially those with mild RLS. Side effects include sleepiness, ataxia, and weight gain. Opioid treatment for RLS has been described as effective but, aside from the stigma of taking controlled substances regularly, side effects may include nausea, sedation, constipation, and dysequilibrium. Iron supplementation is therapeutic in some patients with iron deficiency and RLS.

Preliminary anecdotal data suggest that topiramate reduces RLS symptoms. Topiramate has several potential mechanisms of action including enhancement of GABA-mediated inhibition, which may account for the observed benefit in patients with RLS.

Topiramate may be a better alternative than the currently available treatments to suppress RLS symptoms. Like gabapentin, it offers the possibility of decreasing RLS symptoms while also diminishing pain, especially in those patients who have limb pain from neuropathy, radiculopathy, or other causes. Unlike gabapentin, topiramate may help overweight patients with RLS lose weight, if anedotal reports on weight reduction with the medication are correct.

• Study Type: Interventional
• Enrollment: 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • NeuroCare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The symptoms of each subject must meet the diagnostic criteria of the International RLS Study Group
• More than five periodic leg movements per hour recorded during baseline polysomnography (PSG)
• Each subject must discontinue all treatments for RLS and agreed not to take other RLS treatments during the study

Exclusion Criteria:

• Clinically unstable medical problems
• History of nephrolithiasis
• Progressive neurologic disease
• Inadequate therapeutic response from two previous treatment regimens for RLS
• Subjects unable to discontinue medications known to cause or suppress RLS
• Subjects with sleep apnea syndrome
• Subjects consuming daily more than three beverages containing caffeine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Educational/Counseling/Training
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The average number of periodic leg movements during three consecutive nights of actigraphy beginning at the end of the double blind phase

Secondary Outcome Measures

Outcome Measure
Proportion of time in bed without leg movements during the three consecutive nights of actigraphy beginning at the end of the double blind phase
SF-36 at the last visit of the double blind phase
Score on the RLS Rating Scale (modified) questionnaire at the last visit of the double blind phase
Periodic leg movements during sleep and wakefulness during the PSG recorded at the end of the double blind phase
PSG measures including periodic leg movement arousal index, latency until sustained sleep, sleep efficacy, and wake after sleep onset
Sleep diaries at the last double-blind visit
Epworth sleepiness scale at the last double-blind visit

Collaborators and Investigators

• Sponsor: Neurocare
• Collaborators: Ortho-McNeil Pharmaceutical
• Investigators: Principal Investigator: Michael P Biber, MD, NeuroCare

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Study Completion: April 1, 2005

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Estimate): December 16, 2005
• Last Update Submitted That Met QC Criteria: December 15, 2005
• Last Verified: September 1, 2005

More Information

Terms related to this study

• Keywords: Polysomnography; Restless Legs Syndrome; Actigraphy; Topiramate
• 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; Hypoglycemic Agents; Physiological Effects of Drugs; Anticonvulsants; Topiramate
• Other Study ID Numbers: CAPSS-178