Treatment of Restless Legs Syndrome, Recruiting Patients for Study

OBJECTIVE:

To evaluate the efficacy of botulinum toxin, type A, (BoNT) for the treatment of primary Restless legs syndrome (RLS). We hypothesize that BoNT will be effective at decreasing the deep sensory discomfort of RLS.

STUDY POPULATION:

This protocol is a proof of principle double-blind randomized placebo-BoNT crossover outpatient pilot study of 6 patients diagnosed with moderate to very severe primary RLS.

DESIGN:

All subjects will be evaluated at the NIH Clinical Center by a study investigator to determine eligibility for participation in this protocol. We will obtain a complete medical history, and perform a neurological examination, along with laboratory screening studies. Subjects eligible to participate will receive baseline ratings using the Restless Legs Rating Scale (RLS-RS). Subjects will then be randomized to receive electromyography (EMG)-guided injections of up to 90 units of BoNT or an equivalent volume of saline in each lower extremity, in symptomatic muscles. Subjects will then receive follow up ratings at week 2 and 4 following each injection. Twelve weeks after receiving the first injection, subjects will crossover to receive the alternative compound with similar follow up ratings.

OUTCOME MEASURES:

Primary outcome measure will be mean change from baseline at 4 weeks post-injection on the RLS-RS for placebo and BoNT, while secondary outcome will evaluate patient reported Clinical Global Impression of Change (CGI-C) scores for each group, duration of effect, and adverse events. Only descriptive statistics will be performed on this limited data sample.

• Primary outcome measure will be the mean change from baseline in the RLS scale at week 2 following placebo/BTX injections

OBJECTIVE:

To evaluate the efficacy of botulinum toxin, type A, (BoNT) for the treatment of primary Restless legs syndrome (RLS). We hypothesize that BoNT will be effective at decreasing the deep sensory discomfort of RLS.

STUDY POPULATION:

This protocol is a proof of principle double-blind randomized placebo-BoNT crossover outpatient pilot study of 6 patients diagnosed with moderate to very severe primary RLS.

DESIGN:

All subjects will be evaluated at the NIH Clinical Center by a study investigator to determine eligibility for participation in this protocol. We will obtain a complete medical history, and perform a neurological examination, along with laboratory screening studies. Subjects eligible to participate will receive baseline ratings using the Restless Legs Rating Scale (RLS-RS). Subjects will then be randomized to receive electromyography (EMG)-guided injections of up to 90 units of BoNT or an equivalent volume of saline in each lower extremity, in symptomatic muscles. Subjects will then receive follow up ratings at week 2 and 4 following each injection. Twelve weeks after receiving the first injection, subjects will crossover to receive the alternative compound with similar follow up ratings.

OUTCOME MEASURES:

Primary outcome measure will be mean change from baseline at 4 weeks post-injection on the RLS-RS for placebo and BoNT, while secondary outcome will evaluate patient reported Clinical Global Impression of Change (CGI-C) scores for each group, duration of effect, and adverse events. Only descriptive statistics will be performed on this limited data sample.

• INCLUSION CRITERIA:
• Age 18 or older.
• Diagnosed with primary RLS based on presence of a characteristic clinical history and the International restless legs syndrome study group (IRLSSG) diagnostic criteria.
• A minimum score of 11 on the RLS rating scale (this is equivalent to a minimum rating of moderate severity).
• If subjects are on medications for RLS, the medication regimen must be stabilized for greater than 6 weeks prior to entering the study.

EXCLUSION CRITERIA:

• Subjects with any abnormal findings on neurological exam.
• Subjects with a dermatologic disorder that precludes injections in the legs.
• Subjects with a positive urine pregnancy test.
• Subjects without the capacity to give informed consent.
• Subjects taking aminoglycosides, chloroquine, clindamycin, hydroxychloroquine, magnesium sulfate, quinidine, or an anticoagulant.
• Subjects with abnormal clinical chemistry, hematology or urine drug screen by laboratory testing.