Clinical trial NCT00200941: Efficacy and Safety Study of Topiramate to Treat Restless Legs Syndrome
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Restless Legs Syndrome
Keywords: Restless Legs Syndrome
Topiramate
Actigraphy
Polysomnography
Lead sponsor: Neurocare
Sponsor class: OTHER
Collaborators: name: Ortho-McNeil Pharmaceutical
First posted: 2005-09-20
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: ECT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: The average number of periodic leg movements during three consecutive nights of actigraphy beginning at the end of the double blind phase
Secondary outcomes:
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
measure: SF-36 at the last visit of the double blind phase
measure: Score on the RLS Rating Scale (modified) questionnaire at the last visit of the double blind phase
measure: Periodic leg movements during sleep and wakefulness during the PSG recorded at the end of the double blind phase
measure: PSG measures including periodic leg movement arousal index, latency until sustained sleep, sleep efficacy, and wake after sleep onset
measure: Sleep diaries at the last double-blind visit
measure: Epworth sleepiness scale at the last double-blind visit
Other outcomes:
Locations:
city: Newton
country: United States
facility: Neurocare
state: Massachusetts
Study officials:
affiliation: Neurocare
name: Michael P Biber, MD
role: PRINCIPAL_INVESTIGATOR
References: