Botulinum Toxin to Treat Restless Legs Syndrome

Pilot Study of Botulinum Toxin Type A for the Treatment of Restless Legs Syndrome

This study will test whether botulinum toxin (Botox) may relieve the uncomfortable sensations patients with restless legs syndrome (RLS) experience. RLS is a common movement disorder that causes sensory discomfort and restlessness, most often in the legs, which improves with movement. Although medications are available to treat the disorder, many people experience side effects that prevent them from continuing on the medication. The Food and Drug Administration has approved Botox for other movement disorders and for some cosmetic uses.

People 18 years of age or older with moderate to severe RLS who have been taking RLS medications for more than 6 weeks before entering the study may be eligible to participate. Candidates are screened with a medical history, physical and neurological examinations, blood tests and, for women who can become pregnant, a urine pregnancy test.

Participants are randomly assigned to receive injections of either Botox or placebo (salt water) into up to nine areas of the legs. The correct location of the muscles to be injected is determined by electromyography (EMG), a test that measures the electrical activity of muscles. For surface EMG, electrodes (small metal disks) are filled with a conductive gel and taped to the skin. Needle EMG involves inserting a needle into a muscle. Both methods are used in this study.

At 2 and 4 weeks after the injections, subjects are interviewed by telephone and asked to describe their symptoms, side effects and any improvement they may have noticed. After 12 weeks they return to NIH for injections with the alternate compound; that is, those who received Botox previously are given placebo for the second set of injections, and vice-versa. Subjects are again contacted by telephone 2 and 4 weeks after the injections to report their symptoms, side effects and benefits.

Study Overview

• Status: Completed
• Conditions: Restless Legs Syndrome
• Intervention / Treatment: Drug: Botulinum Toxin A

Detailed Description

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:

The primary outcome measure will be mean change from baseline at 4 weeks post-injection on the RLS-RS for placebo and BoNT, while the other pre specified outcomes 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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botulinum Toxin A; Injection of onabotulinumtoxinA	Drug: Botulinum Toxin A; Maximum dose of 90 units/leg was injected.; Other Names: onabotulinum toxin
Placebo Comparator: Placebo (saline); Injection of saline placebo	Drug: Botulinum Toxin A; Maximum dose of 90 units/leg was injected.; Other Names: onabotulinum toxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Restless Legs Syndrome Rating Scale	Primary outcome measure will be the mean change from baseline in RLS scale at week 2 following placebo/BTX injections. Scoring criteria are: Mild (score 1-10); Moderate (score 11-20); Severe (score 21-30); Very severe (score 31-40).	Week 2 and Week 4 for each intervention (vs. baseline)

Collaborators and Investigators

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Fatta Nahab, MD, NINDS/NIH

Publications and helpful links

General Publications

• Blasi J, Chapman ER, Link E, Binz T, Yamasaki S, De Camilli P, Sudhof TC, Niemann H, Jahn R. Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature. 1993 Sep 9;365(6442):160-3. doi: 10.1038/365160a0.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: May 25, 2007
• First Submitted That Met QC Criteria: May 25, 2007
• First Posted (Estimate): May 28, 2007

Study Record Updates

• Last Update Posted (Estimate): April 26, 2012
• Last Update Submitted That Met QC Criteria: April 25, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Botulinum Toxin; RLS; Restless Leg Syndrome
• 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; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 070160; 07-N-0160 (Other Identifier: Intramural NINDS Protocol # 07-N-0160)