Talampanel to Treat Parkinson's Disease
This study will evaluate the effects of the experimental drug talampanel on dyskinesias (involuntary movements) that develop in patients with Parkinson's disease as a result of long-term treatment with levodopa (Sinemet). The drug will be tested alone and in combination with amantadine-a drug commonly used to alleviate dyskinesias.
Patients between 21 and 80 years of age with Parkinson's disease and dyskinesias may be eligible for this study.
Screening and baseline evaluation. Participants are evaluated with a medical history, physical and neurologic examinations, blood and urine tests, electrocardiogram (EKG) and pregnancy test, if applicable. A chest x-ray and MRI or CT scan of the brain are done if needed. Patients stop taking all antiparkinsonian medications for one month (2 months if taking Selegiline) before the study begins and throughout its duration, except for certain medicines allowed, including Sinemet, Mirapex and Requip. Amantadine can be taken up to 1 week before beginning the study.
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 it 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. At given times during the infusion, saline is given instead of Sinemet. The infusions usually begin in the early morning and continue until evening. Patients resume taking Sinemet between infusions. (Patients who have had dosing infusions in the last 3 months do not have to undergo this phase of the study.)
After the dose-finding phase, patients are randomly assigned to take placebo (a "sugar pill") or talampanel. Those taking talampanel also receive amantadine at their usual dosages. At some point in the study, amantadine is replaced with placebo. Patients in the talampanel group also receive placebo for portions of the study.
Active study phase. At study weeks 1, 5 and 7, patients are admitted to the Clinical Center overnight for a levodopa infusion with talampanel or placebo. The day before the infusion, patients have a brief physical examination, blood and urine tests, an EKG, and a review of symptoms or changes in their condition. The next day, they receive an infusion of levodopa at the dose determined in the dose-finding phase. Then they take a pill containing either talampanel or placebo. Their parkinsonian symptoms and dyskinesias are evaluated and videotaped every 30 minutes for about 6 hours. Blood is drawn and an EKG is obtained. At the end of the infusions and ratings, patients resume their regular Parkinson's medications and are given a new supply of study medications to take home.
At weeks 2, 3, 4 and 6, patients come to the Clinical Center for a review of drug side effects. They have blood drawn and receive a new supply of study medications that last until the next visit.
Follow-up. Two weeks after the study ends, patients are contacted by phone for a review of side effects or they return to the clinic for an evaluation.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Official Title:||AMPA Receptor Antagonist Treatment of Parkinson's Disease|
|Study Start Date:||April 2005|
|Estimated Study Completion Date:||February 2006|
Objective: to evaluate the acute effects of talampanel, a novel antagonist of AMPA type glutamate receptors, on the severity of parkinsonian signs and levodopa-associated motor response complications.
Study Population: patients with moderately advanced Parkinson's disease and dopaminergic therapy related motor complications, between the age of 21 and 80.
Study Design: randomized, controlled, proof-of-principle pilot study lasting approximately 7 weeks.
Study Outcome Parameters: the pharmacokinetic characteristics of orally administered talampanel will be measured by means of plasma drug assays, its therapeutic efficacy will be evaluated using validated motor function scales, and safety will be monitored by means of frequent clinical evaluations and laboratory tests.
|United States, Maryland|
|National Institute of Neurological Disorders and Stroke (NINDS)|
|Bethesda, Maryland, United States, 20892|