This study will evaluate the effectiveness of a skin patch formulation of the dopamine
agonist Lisuride in controlling parkinsonian symptoms and dyskinesias (involuntary movements)
caused by levodopa. Lisuride is currently available in tablet form; this study will test
whether a patch formulation that provides continuous stimulation of the dopamine receptors
will better control disease symptoms.
Patients between 40 and 80 years old with Parkinson's disease and dyskinesias may be eligible
for this 4-month study. Participants undergo the following procedures:
Screening and baseline evaluation: Participants are evaluated with a medical history,
physical examination, neurologic evaluation, blood tests, urinalysis, and electrocardiogram.
A chest X-ray and MRI or CT scan of the brain are done, if needed. If possible, patients stop
taking all antiparkinsonian medications except levodopa (Sinemet) for 1 month (2 months for
Selegiline) before the study begins and throughout its duration.
Dose-finding phase: Patients are admitted to the NIH Clinical Center for 2 to 3 days for a
levodopa "dose-finding" procedure. For this test, patients stop taking Sinemet and instead
have levodopa infused through a vein. During the infusions, the drug dose is increased slowly
until parkinsonian symptoms improve or unacceptable side effects occur or the maximum study
dose is reached. Symptoms are monitored frequently. (Patients who have had dosing infusions
in the last 3 months do not have to undergo this phase of the study.)
Active study phase: Patients are randomly assigned to one of two treatment groups. One group
receives a placebo (a patch with no active drug) and a patch that contains Lisuride; the
other group receives placebo throughout the entire study. Patients are instructed on how to
apply the patches. During the first 2 weeks of this study phase, the number of patches
containing active drug is gradually increased until the individual's optimum dose is reached.
Patches are changed about every 2 days. During this time, intake of other antiparkinsonian
medications is tapered down and patients are evaluated frequently. For the next 3 months,
patients wear the patches continuously at the optimum dose. The patches are changed every 2
days or once a week, depending on the individual patient's need. Two levodopa infusion
studies are done in the active study phase as they were in the dose-finding phase - at the
beginning of the dose escalation phase and again at the end of the dose maintenance phase. In
addition, patients are tested for their ability to perform different motor tasks.
Sleep studies: Because oral Lisuride can cause excessive sleepiness, some patients are asked
to participate in a sleep study to evaluate sleep patterns during the night and daytime
sleepiness. The subject's brain, muscles, and breathing are continuously monitored during
sleep. Also, an electroencephalogram (EEG) is done to record brain waves while the subject
lies quietly, breathes deeply, watches flashes of light, sleeps, or performs a task.
Safety checks: Patients are monitored closely for safety with a history of side effects,
blood tests, and ECG each time a new supply of study drug is dispensed.
Follow-up: 2 weeks after completing the active phase of the study, patients are contacted by
phone for a follow-up evaluation.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)