Riluzole to Treat Parkinson's Disease

NCT00013624 | Completed Phase 2

• 2 other identifiers: 01011801-N-0118
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the effects of the drug riluzole on Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term treatment with levodopa. Riluzole blocks the action of the chemical messenger glutamate, thought to be involved in producing Parkinson's symptoms. The drug is currently approved to treat amyotrophic lateral sclerosis, another neurologic condition. Patients with relatively advanced Parkinson's disease between 20 and 80 years of age may be eligible for this 4-week study. Participants will have a complete medical history and physical examination, and a detailed neurological evaluation. The evaluations will include blood tests and an electrocardiogram, and possibly brain magnetic resonance imaging (MRI), CT scan, and chest X-ray. Participants will, if possible, stop taking all antiparkinsonian medications except levodopa (Sinemet) for one month before the study begins and throughout its duration. For the first 1 to 3 days, patients will be admitted to the NIH Clinical Center to undergo a levodopa "dose-finding" procedure. For this study, patients will stop taking their oral Sinemet and instead will have levodopa infused through a vein for up to 8 hours/day. During the infusions, the levodopa dose will be increased slowly until either 1) parkinsonian symptoms improve, 2) unacceptable side effects occur, or 3) the maximum study dose is reached. Symptoms will be monitored frequently to find two infusion rates: 1) one that is less than what is needed to relieve symptoms (suboptimal rate), and 2) one that relieves symptoms but may produce dyskinesias (optimal rate). When the dose-finding phase is completed, treatment will begin. Patients will take riluzole or placebo (a look-a-like pill with no active ingredient) twice a day, along with their regular Sinemet, for 3 weeks. (All participants will receive placebo at some time during the study, and some patients will receive only placebo throughout the entire 4 weeks.) At the end of each week, patients will be readmitted to the hospital and receive the previous week's dose of riluzole or placebo in combination with a levodopa infusion at the rate determined in the dose-finding phase of the study. The procedure for the infusion will be the same as that for the dose-finding phase. The dose of riluzole will be increased until the optimum dose has been achieved or until side effects occur (at which time the dose will be lowered or the drug stopped). Throughout the study, parkinsonian symptoms and dyskinesias will be evaluated using standardized rating scales and blood samples will be drawn periodically to measure drug levels.

Conditions

Parkinson's Disease

Keywords

Riluzole; Dyskinesias; L-Dopa Infusion; Parkinson's Disease

Interventions

IV Levodopa DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females between the ages of 20-80 are eligible for study. Women must be either at least one year post-menopausal, or using an adequate contraceptive method for at least one month prior to and during participation in this study. All will carry the diagnosis of idiopathic Parkinson's disease based on the presence of a characteristic clinical history and neurological findings. All will have relatively advanced disease with levodopa-associated motor response complications, including peak-dose dyskinesias and wearing-off fluctuations.

You may not qualify if:

• The presence or history of any medical condition that can reasonably be expected to subject the patient to unwarranted risk. Any clinically significant laboratory abnormalities including liver enzyme elevations more than two times the upper limit of normal, or neutropenia (wbc less than 3000).
• Parkinson's disease patients exhibiting diphasic or end-of dose dyskinesias or disabling dystonia will be excluded. Patients who are unable to be treated with levodopa/carbidopa alone or with a single, relatively short-acting dopamine agonist will also be excluded.
• Patients with a form of parkinsonism other than idiopathic PD or with a diagnosis of dementia (MMSE less than 24) or major psychiatric disorder (UPDRS \[Part I Item 3\] greater than or equal to 2).
• Patients with unacceptable prior/concomitant medications will also be excluded.
• Since the influence of any investigational compound on the unborn child and reproductive organs is unknown, pregnant women and those not practicing effective means of birth control will be excluded as well.
• Patients with prior bilateral surgical intervention for the treatment of parkinsonian symptoms, i.e. deep brain stimulation, pallidotomy, fetal tissue transplantation as well as patients must at risk for hypotension, cardiac arrhythmia, and/or myocardial ischemia secondary to intravenous levodopa challenge will be excluded.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institute of Neurological Disorders and Stroke (NINDS)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Mizuno Y, Mori H, Kondo T. Parkinson's disease: from etiology to treatment. Intern Med. 1995 Nov;34(11):1045-54. doi: 10.2169/internalmedicine.34.1045.

  PMID: 8774962 BACKGROUND

• Chase TN, Oh JD, Blanchet PJ. Neostriatal mechanisms in Parkinson's disease. Neurology. 1998 Aug;51(2 Suppl 2):S30-5. doi: 10.1212/wnl.51.2_suppl_2.s30.

  PMID: 9711978 BACKGROUND

• Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci. 1973 Dec;20(4):415-55. doi: 10.1016/0022-510x(73)90175-5. No abstract available.

  PMID: 4272516 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Dyskinesias

Interventions

Levodopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 24, 2001
• First Posted: March 26, 2001
• Study Start: March 1, 2001
• Study Completion: March 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-03

Locations

US (1)