Lisuride Patch to Treat Parkinson's Disease
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.
Drug: Intravenous Levodopa
Drug: Lisuride Transdermal System
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Transcutaneous Lisuride Therapy of Parkinson's Disease|
- Change in parkinsonian severity variance.
- Change in dyskinesia severity.
- Change in antiparkinsonian efficacy half-time for levodopa.
- Change in parkinsonian severity.
- Change in optimal oral levodopa requirement.
- Change in patient diary rating.
- Change in daytime somnolence.
|Study Start Date:||August 2004|
|Estimated Study Completion Date:||March 2007|
Introduction: Parkinson's disease (PD) is a progressive degenerative disease of unknown etiology. Treatment is symptomatic and the most successful approach has been to replace the missing dopamine through administration of its precursor levodopa. As the disease progresses, the usefulness of this approach gradually diminishes, and motor complications become a source of significant disability. Although a number of pharmacological strategies have attempted to improve this situation, none has yet proven fully satisfactory. A novel transcutaneous formulation of the dopamine agonist lisuride will be used to test the ability of this approach to reduce levodopa-induced motor response complications.
Objective: The objective of this study is to evaluate the risks and benefits of continuous dopaminomimetic replacement therapy in patients with advanced Parkinson's disease.
Study population: Approximately 22 moderately advanced parkinsonian patients will be enrolled into a randomized, placebo-controlled, double-blind, proof-of-principle study, lasting approximately 16 weeks. Lisuride efficacy will be assessed through the use of validated motor function scales. Safety will be monitored by means of frequent clinical evaluations and laboratory tests.
Anticipated Risks and Benefits: The potential risks associated with this study amount to only a minor increase over minimal risk and are primarily associated with adverse reactions to the medications involved. Lisuride has been approved for use in Europe for more than 20 years and has a wide margin of safety. Patients receiving drug could benefit from improvement of their clinical condition; those on placebo will also receive proper medical care that may lead to a better quality of life.
Outcome Estimate and Potential Meaning for the Field: This study should further the understanding of mechanisms contributing to motor disability in patients with PD and thus lead to the development of improved therapeutic interventions for this disorder and for associated motor response complications.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|