This study will evaluate the effects of the drug riluzole on Parkinson's disease symptoms and
on dyskinesias (involuntary movements) that develop as a result of long-term treatment with
levodopa. Riluzole blocks the action of the chemical messenger glutamate, thought to be
involved in producing Parkinson's symptoms. The drug is currently approved to treat
amyotrophic lateral sclerosis, another neurologic condition.
Patients with relatively advanced Parkinson's disease between 20 and 80 years of age may be
eligible for this 4-week study. Participants will have a complete medical history and
physical examination, and a detailed neurological evaluation. The evaluations will include
blood tests and an electrocardiogram, and possibly brain magnetic resonance imaging (MRI), CT
scan, and chest X-ray.
Participants will, if possible, stop taking all antiparkinsonian medications except levodopa
(Sinemet) for one month before the study begins and throughout its duration. For the first 1
to 3 days, patients will be admitted to the NIH Clinical Center to undergo a levodopa
"dose-finding" procedure. For this study, patients will stop taking their oral Sinemet and
instead will have levodopa infused through a vein for up to 8 hours/day. During the
infusions, the levodopa dose will be increased slowly until either 1) parkinsonian symptoms
improve, 2) unacceptable side effects occur, or 3) the maximum study dose is reached.
Symptoms will be monitored frequently to find two infusion rates: 1) one that is less than
what is needed to relieve symptoms (suboptimal rate), and 2) one that relieves symptoms but
may produce dyskinesias (optimal rate).
When the dose-finding phase is completed, treatment will begin. Patients will take riluzole
or placebo (a look-a-like pill with no active ingredient) twice a day, along with their
regular Sinemet, for 3 weeks. (All participants will receive placebo at some time during the
study, and some patients will receive only placebo throughout the entire 4 weeks.) At the end
of each week, patients will be readmitted to the hospital and receive the previous week's
dose of riluzole or placebo in combination with a levodopa infusion at the rate determined in
the dose-finding phase of the study. The procedure for the infusion will be the same as that
for the dose-finding phase. The dose of riluzole will be increased until the optimum dose has
been achieved or until side effects occur (at which time the dose will be lowered or the drug
stopped).
Throughout the study, parkinsonian symptoms and dyskinesias will be evaluated using
standardized rating scales and blood samples will be drawn periodically to measure drug
levels.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)