Efficacy and Safety Study of Topiramate to Treat Restless Legs Syndrome

Sponsor

Neurocare (Other)

Overall Status

Completed

CT.gov ID

NCT00200941

Collaborator

Ortho-McNeil Pharmaceutical (Industry)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Restless Legs Syndrome	Drug: Topiramate	Phase 4

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 Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Educational/Counseling/Training

Official Title:

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

Study Start Date :

Aug 1, 2001

Study Completion Date :

Apr 1, 2005

Outcome Measures

Primary Outcome Measures

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

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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