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Botulinum Toxin to Treat Restless Legs Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00479154
Recruitment Status : Completed
First Posted : May 28, 2007
Results First Posted : April 26, 2012
Last Update Posted : April 26, 2012
Information provided by (Responsible Party):
Fatta Nahab, National Institutes of Health Clinical Center (CC)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Restless Legs Syndrome Drug: Botulinum Toxin A Phase 1 Phase 2

Detailed Description:


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.


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.


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.


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study of Botulinum Toxin Type A for the Treatment of Restless Legs Syndrome
Study Start Date : May 2007
Actual Primary Completion Date : April 2008
Actual Study Completion Date : April 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Botox Restless Legs

Arm Intervention/treatment
Experimental: Botulinum Toxin A
Injection of onabotulinumtoxinA
Drug: Botulinum Toxin A
Maximum dose of 90 units/leg was injected.
Other Name: onabotulinum toxin

Placebo Comparator: Placebo (saline)
Injection of saline placebo
Drug: Botulinum Toxin A
Maximum dose of 90 units/leg was injected.
Other Name: onabotulinum toxin

Primary Outcome Measures :
  1. Change in Restless Legs Syndrome Rating Scale [ Time Frame: Week 2 and Week 4 for each intervention (vs. baseline) ]
    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).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • 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.


  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00479154

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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Principal Investigator: Fatta Nahab, MD NINDS/NIH
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Responsible Party: Fatta Nahab, Assistant Clinical Investigator, National Institutes of Health Clinical Center (CC) Identifier: NCT00479154    
Other Study ID Numbers: 070160
07-N-0160 ( Other Identifier: Intramural NINDS Protocol # 07-N-0160 )
First Posted: May 28, 2007    Key Record Dates
Results First Posted: April 26, 2012
Last Update Posted: April 26, 2012
Last Verified: April 2012
Keywords provided by Fatta Nahab, National Institutes of Health Clinical Center (CC):
Restless Leg Syndrome
Botulinum Toxin
Additional relevant MeSH terms:
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Psychomotor Agitation
Restless Legs Syndrome
Pathologic Processes
Neurologic Manifestations
Nervous System Diseases
Psychomotor Disorders
Neurobehavioral Manifestations
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Mental Disorders
Botulinum Toxins
Botulinum Toxins, Type A
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents