Levetiracetam Treatment of L-dopa Induced Dyskinesias
Status:
Completed
Trial end date:
2005-10-01
Target enrollment:
Participant gender:
Summary
This study will evaluate the effects of levetiracetam (Keppra (Trademark) on Parkinson's
disease symptoms and on dyskinesias (involuntary movements) that develop as a result of
long-term treatment with levodopa. Levetiracetam blocks certain protein receptors on brain
cells and thus can change the spread of brain signals believed to be affected in patients
with Parkinson's disease.
Patients between 30 and 80 years of age with relatively advanced Parkinson's disease and
dyskinesias due to levodopa therapy may be eligible for this 6-week study.
Screening and baseline evaluation - Participants are evaluated with a medical history,
physical examination and neurologic evaluation, blood tests, urinalysis, electrocardiogram
(EKG), 24-hour holter monitor (heart monitoring), and cardiology consultation. 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 one month (2 months if taking
Selegiline) before the study begins and throughout its duration. (If necessary, patients may
use short-acting agents, such as Mirapex, Requip or Amantadine.)
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 take levetiracetam or placebo ("sugar
pill") twice a day for 6 weeks. At the end of weeks 1, 2 4, and 5, patients come to the
clinic for blood tests, an EKG, and a review of adverse side effects. At the end of weeks 3
and 6, patients are hospitalized to study the response to treatment. They again stop taking
Sinemet and selegiline and their ability to perform motor tasks is evaluated. They are then
placed on an L-dopa infusion for 10 hours. Placebo may be infused at various times instead of
L-dopa. Motor symptoms are evaluated several times during the infusion. Blood is drawn once
during the infusion for research studies.
Lumbar puncture - Patients undergo a lumbar puncture (spinal tap) at the end of weeks 1 and 4
to measure certain brain chemicals and drug levels. For this test, a local anesthetic is
given and a needle is inserted in the space between the vertebrae in the lower back. About 2
tablespoons of fluid is collected through the needle.
Magnetic resonance imaging (MRI) - Patients with changing disease activity may undergo MRIs
at baseline, at the end of week 1 and at the end of the study to show changes in the brain.
The patient lies in a narrow cylinder (the scanner) that uses radio waves and a magnetic
field to produce images of the brain, which show structural and chemical changes.
Follow-up - 2 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.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)