Effect of Ropinirole on Spinal Cord Reflexes and Restless Legs Syndrome
Condition: Restless Legs Syndrome
MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome
Study type: Observational

Summary: 
      This study will examine the effects of the drug Ropinirole on spinal cord reflexes and on
      symptoms of restless legs syndrome (RLS). Patients with RLS have uncomfortable sensations in
      the legs, usually in the evening or early part of the night. Most patients also have periodic
      involuntary leg movements. The condition tends to worsen over time, resulting in severe
      discomfort and sleep disturbances. Ropinirole affects chemical messengers thought to be
      involved in spinal cord function and in modulating RLS symptoms.

      Healthy normal volunteers and patients with RLS between 18 and 80 years of age may be
      eligible for this study. Patients must have mild to moderate RLS and periodic limb movements.
      All candidates will be screened with a medical history, physical and neurological
      evaluations, electromyogram (see below), polysomnogram (see below), electrocardiogram (ECG),
      and blood and urine tests. They may also have magnetic resonance imaging (MRI) or
      computerized tomography (CT) scans and a chest x-ray. Participants must stop taking all
      medications prohibited by the study for at least 1 week before the study starts and
      throughout its duration.

      The study will last approximately 2 to 3 weeks for healthy volunteers and 7 to 8 weeks for
      patients. Participants will undergo the following baseline evaluations:
      electroencephalography (EEG), a measure of brain wave activity; polysomnography (PSG), an
      overnight sleep study; electromyography (EMG), a measure of muscle activity; and spinal
      flexor reflex studies (spinal cord responses to electrical stimulation). For these studies,
      several electrodes are attached to the scalp or to the legs and arms using a cream that helps
      conduct brain signals through the cables to be recorded. The nervous system activity can be
      assessed at rest or after stimulation with an electric current. For EMG, a small needle is
      inserted into a few muscles and the subject is asked to relax or to contract the muscles. The
      electrical activity of the muscle cells is recorded and analyzed by a computer. Spinal flexor
      reflex studies usually involve stimulating the nerves in the legs with very brief electric
      currents of mild to moderate intensity. Flexor reflex studies will be done early in the night
      while the subject is awake and also during sleep. Brain, muscle and breathing activities will
      be monitored continuously during sleep.

      A suggested immobilization test (SIT) will be done around 10 p.m. During the test, the
      subject sits still for about 1 hour, while the leg muscle activity is recorded using special
      electronic devices attached to the skin. At the end of the test, volunteers will be asked
      questions about symptoms they may have experienced during the test, and patients will be
      asked questions about their RLS symptoms during the test.

      After the baseline tests, participants will be randomly assigned to take either Ropinirole
      tablets or a placebo (a look-alike inactive substance) daily for 5 weeks. They will be
      admitted to the NIH Clinical Center for 3 to 4 nights at the end of the second week and for 2
      nights at the end of the study to repeat the baseline tests described above. Volunteers will
      take Ropinirole or placebo daily for 1 week. They will be admitted to the Clinical Center for
      3 to 4 days at the beginning and then at the end of the study for repeat testing.

      Medical examinations, ECGs and blood tests will be done at various times during the study for
      safety monitoring. Patients' blood pressure will be monitored weekly. Small amounts of blood
      will be drawn up to three times each day for routine studies, research and drug levels.
      Throughout the study volunteers will complete questionnaires for evaluation of possible RLS
      symptoms, and patients will have their symptoms assessed using a RLS Severity Rating Scale.
      Two weeks after the study ends, participants will be interviewed by telephone about any
      adverse experiences.
    

Detailed description: 
      The objective of this study is to evaluate the effects of stimulation of dopaminergic D2, D3
      receptors on spinal cord excitability and on the severity of symptoms in patients with mild
      to moderately advanced restless legs syndrome. In a controlled proof-of-principle clinical
      study, the acute efficacy of ropinirole will be assessed through the use of validated
      electrophysiological tests and severity scales. Safety will be monitored by means of frequent
      clinical evaluations and laboratory tests.
    

Keywords: Dopamine; Spinal Physiology; Flexor Reflex; Ropinirole; Motor Control; Dopaminergic; Restless Legs