ACP-103 to Treat Parkinson's Disease
This study will evaluate the effects of an experimental drug called ACP-103 on Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term levodopa treatment. ACP-103 changes the spread of certain brain signals that are affected in patients with Parkinson's disease.
Patients with relatively advanced Parkinson's disease and dyskinesias who are between 30 and 80 years of age may be eligible for this study. Candidates are screened with a complete medical history and physical examination, neurological evaluation, blood and urine tests, and electrocardiogram (ECG). A brain magnetic resonance imaging (MRI) scan, CT scan, and chest x-ray may be done if medically indicated.
Patients enrolled in the study will, if possible, stop taking all antiparkinsonian medications for one month (2 months for Selegiline) before the study begins and throughout its duration. Exceptions are Sinemet (levodopa/carbidopa), Mirapex (pramipexole) and Requip (ropinirole).
Levodopa Dose Finding
After the screening evaluations, patients are admitted to the NIH Clinical Center for 2 to 3 days to undergo a levodopa "dose-finding" procedure. For this test, patients stop taking Sinemet and instead have levodopa infused through a vein. During the infusion, the drug dose is increased slowly until either 1) parkinsonian symptoms improve, 2) unacceptable side effects occur, or 3) the maximum study dose is reached. Side effects are monitored closely during the infusions, and parkinsonian symptoms are evaluated frequently during and after the infusions. The infusions usually begin early in the morning and continue until evening. Once the infusion is finished, patients resume taking their regular oral Sinemet dose. The infusions are repeated once a week during 1-day inpatient evaluations.
Patients are randomly assigned to take either ACP-103 followed by placebo (a look-alike pill with no active ingredient) once a week for 10 weeks or vice versa (placebo followed by ACP-103). Patients are admitted to the Clinical Center for each dose. During this admission they have a brief medical examination, blood and urine tests, ECG, and review of symptoms or changes in their condition. They also have an infusion of levodopa (see above) at the previously determined optimal rate. Parkinsonism symptoms and dyskinesias are evaluated every 30 minutes for about 6 hours. At the end of the infusions and ratings, patients are discharged home with their regular Parkinson's medications until the following visit.
Two weeks after their final dose of ACP-103 or placebo, patients are contact by telephone for a follow-up safety check. At that time, the investigator may ask the patient to return to the clinic for closer evaluation.
Drug: Intravenous Levodopa
|Study Design:||Primary Purpose: Treatment|
|Official Title:||5HT2A/C Serotonin Blockade in Parkinson's Disease|
|Study Start Date:||June 2004|
|Estimated Study Completion Date:||November 2007|
Introduction: In Parkinson's disease (PD), levodopa-induced dyskinesias and motor fluctuations are frequent, disabling complications. Therefore, it is imperative to find nondopaminergic approaches to the palliation of parkinsonian signs. Previously, we demonstrated that drugs that block 5HT2A receptors benefit motor dysfunction in parkinsonian animals.
Objective: To test our hypothesis that blockade of serotonin 2A/2C receptors (5HT2A/C) will lessen the severity of parkinsonian signs and levodopa-associated motor response complications in PD patients.
Methods: In a placebo-controlled, proof-of-principle study, the effect of the 5HT2A/C receptor inverse agonist ACP-103 on levodopa induced motor complications and parkinsonian signs will be assessed in up to 20 patients with moderately advanced Parkinson's disease. 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.
Risks and benefits: Risks involved in this study are a minor increase over minimal risks and are deemed reasonable in relation to potential benefits. This investigation should lead to a better understanding of the pathophysiology and treatment of levodopa-induced motor complications in PD.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|