Botulinum Toxin to Treat Restless Legs Syndrome
Condition: Restless Legs Syndrome
MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

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.
    

Intervention name(s): Botulinum Toxin A
Intervention type(s): Drug
Intervention description(s): Maximum dose of 90 units/leg was injected.
Other intervention name(s): onabotulinum toxin
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Restless Leg Syndrome; Botulinum Toxin; RLS