Protocol Number: 04-N-0101

Title:

Levetiracetam Treatment of L-dopa Induced Dyskinesias

Number:

04-N-0101

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.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Patients who meet all of the following inclusion criteria will be able to participate in the study:

1. Patient is between the ages of 30 and 80, inclusive;

2. Patient has been diagnosed with idiopathic Parkinson's disease based on the presence of a characteristic clinical history and neurological findings;

3. Patient has relatively advanced disease with levodopa-associated motor response complications, including peak-dose dyskinesias and wearing-off fluctuations ;

4. Patient is willing to adhere to protocol requirements as evidenced by written, informed consent.

EXCLUSION CRITERIA:

Patients meeting any of the following exclusion criteria will not be enrolled or immediately withdrawn from the study, as appropriate:

1. Patient has a history of any medical condition that can reasonably be expected to subject them to unwaranted risk;

2. Patient has clinically significant laboratory abnormalities including impaired renal function (CL(cr) equals 30-50 ml/min.);

3. Patient is uable to br treated with levodopa/carbidopa alone or with a single, relatively short-acting dopamine agonist, such as pramipexole or ropinirole;

4.Patient is taking a prohibited concomitant medication;

5. Patient has not been using or was not continuing to use an adequate contraceptive method for the last 30 days, or is not at least one year post-menopausal (if female);

6. Patient is pregnant or breastfeeding;

7. Patient is implanted with bilateral deep brain stimulators;

8. Patient has prior pallidotomy or other ablative surgeries for treatment of PD;

9. Patient has cognitive impairment (MMSE less than 25);

10. Patient has participated in a clinical study with an investigational drug within the last 30 days;

11. Patient has a condition (such as active drug or alcohol abuse) that, in the opinion of the investigators, would interfere with compliance or safety;

12. Patient is unwilling to sign an informed consent or to comply with protocol requirements;

13. Patient has a history of psychiatric illness.

Special Instructions: Currently Not Provided

Keywords:

Parkinson's Disease

Keppra

Motor Fluctuations

Intravenous Levodopa

Antiparkinsonian Response

Recruitment Keywords:

Parkinson Disease

PD

Conditions:

Dyskinesias

Parkinson Disease

Investigational Drug(s):

Intravenous Levodopa

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Related Articles, Links No abstract Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci. 1973 Dec; 20(4): 415-55. No abstract available. PMID: 4272516

Kish SJ, Shannak K, Hornykiewicz O. Related Articles, Links Abstract Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. N Engl J Med. 1988 Apr 7; 318(14): 876-80. PMID: 3352672

Mizuno Y, Mori H, Kondo T. Related Articles, Links Abstract Parkinson's disease: from etiology to treatment. Intern Med. 1995 Nov; 34(11): 1045-54. Review. PMID: 8774962

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