Talampanel to Treat Parkinson's Disease

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00108667
First received: April 15, 2005
Last updated: March 3, 2008
Last verified: February 2006
  Purpose

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.


Condition Intervention Phase
Parkinson Disease
Drug: IV Levodopa
Drug: Talampanel
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: AMPA Receptor Antagonist Treatment of Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 40
Study Start Date: April 2005
Estimated Study Completion Date: February 2006
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

Patients who meet all of the following inclusion criteria on Study Day 1 will be eligible to participate in the study:

  1. Between the ages of 21 and 80, inclusive;
  2. Has been diagnosed with idiopathic Parkinson's disease based on the presence of a characteristic clinical history and neurologic findings;
  3. Has relatively advanced disease with levodopa-associated motor response complications, including ratable peak-dose dyskinesias and wearing-off fluctuations;
  4. Patient is willing to adhere to protocol requirements as evidenced by written, informed consent;
  5. Patient is satisfactorily treated with levodopa with or without short acting dopamine agonist.

EXCLUSION CRITERIA:

Patients meeting any of the following exclusion criteria either at Day 0 or during the study will not be enrolled or will be immediately withdrawn from the study, as appropriate:

  1. Has a history of any medical condition that can reasonably be expected to subject them to unwarranted risk, including lung disease, liver disease and clinically significant cardiac arrhythmias and/or myocardial ischemia;
  2. Has clinically significant laboratory abnormalities including liver enzyme elevation; positivity to any of the autoantibodies tested at Screening (ANA, RF, anti-SM, anti-LKM)
  3. Is unable to be treated with levodopa/carbidopa alone or with a single, relatively short-acting dopamine agonist, such as pramipexole or ropinirole;
  4. Unable or unwilling to discontinue a prohibited concomitant medication as listed below; allowable CNS medications will be maintained at a constant dose throughout the study;
  5. Has not been using an adequate contraceptive method for the last 30 days or unwilling to continue, or is not at least one year post-menopausal (if female);
  6. Is pregnant or breastfeeding;
  7. Is implanted with bilateral deep brain stimulators unless the stimulators are turned off during the entire study;
  8. Has prior bilateral pallidotomy or other ablative surgeries for treatment of PD;
  9. Has cognitive impairment (MMSE less than 25);
  10. Has participated in a clinical study with an investigational drug within the last 30 days;
  11. Has a condition (such as active drug or alcohol abuse) that, in the opinion of the investigators, would interfere with compliance or safety;
  12. Is unwilling to sign an informed consent or to comply with protocol requirements.
  13. Unilateral and bilateral pallidotomy
  14. History of alcoholism.
  15. Orthostatic Hypotension
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00108667

Locations
United States, Maryland
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00108667     History of Changes
Other Study ID Numbers: 050139, 05-N-0139
Study First Received: April 15, 2005
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Parkinson's Disease
AMPA Antagonist
Dyskinesias
Glutamate Antagonist
Parkinson Disease
PD

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Levodopa
Excitatory Amino Acid Antagonists
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on April 17, 2014