Effects of Monoamine Reuptake Inhibitor NS2330 in Parkinson's Disease

NCT00006077 | Completed Phase 2

• 2 other identifiers: 00018700-N-0187
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the effects of an experimental drug called NS2330 on Parkinson's disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term treatment with levodopa. This drug prevents the neurotransmitter dopamine from entering nerve cells. Patients between 18 and 75 years old who have moderately advanced Parkinson's disease and motor problems resulting from levodopa therapy may be eligible for this 5-week study. Candidates will have a complete medical history and physical examination with a detailed neurological evaluation. If needed, some patients will undergo a magnetic resonance imaging (MRI) or computerized tomography (CT) scan of the brain and a chest X-ray. All patients will have blood and urine tests and an electrocardiogram (EKG) and will take a written test for evaluation of depression. Patients enrolled in the study will, if possible, stop taking all antiparkinson medications except levodopa (Sinemet) for one month before the study begins and through its duration. For the first 1 to 3 days, patients will undergo a levodopa "dose-finding" procedure. For this study, patients will stop taking their usual oral levodopa medicine and instead will have levodopa infused through a vein for up to 12 hours. During the infusions, the drug dose will be increased slowly until either 1) parkinsonism symptoms improve, 2) dyskinesias appear, 3) unacceptable side effects occur, or 4) the maximum study dose is reached. When the patient's optimal dose is determined, treatment will begin. Patients will take three pills containing NS2330 or placebo (a look-alike pill with no active ingredient) 3 days a week for up to 5 weeks, in addition to their regular levodopa medication. All participants will receive placebo at some point in the study; some patients will receive only placebo throughout the entire 5 weeks. On treatment days, patients will have a brief medical examination before receiving the drug and will then be monitored for side effects for about 6 to 8 hours after taking the drug. At the beginning of weeks 2 and 5, the levodopa infusions will be repeated at the previously determined optimum rate. Throughout the study, parkinsonism symptoms, dyskinesias and depression will be evaluated. Blood and urine samples will be collected each week for standard safety tests, and blood will also be drawn periodically to measure NS2330 levels.

Conditions

Parkinson's Disease

Keywords

Clinical Trial; Dyskinesias; Levodopa Infusion; Parkinson's Disease

Interventions

NS2330 DRUG

Levodopa and Domperidone DRUG

Eligibility Criteria

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

You may qualify if:

• Male and Females are eligible for this study.
• Ages 18-75.
• Women must be at least one year post-menopausal or using an adequate contraceptive method for at least one month prior to and during participation in the study.
• All will carry the diagnosis of idiopathic Parkinson's disease based on the presence of a characteristic clinical history and neurologic findings.
• All will have relatively advanced disease with levodopa-associated motor response complications, including wearing-off fluctuations and peak-dose dyskinesias.

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 twice the upper limit of normal, or neutropenia (wbc less than 4000).
• Patients with diphasic or end-of dose dyskinesias or disabling dystonia.
• Patients who are unable to be treated with levodopa/carbidopa alone or a single, relatively short-acting dopamine agonist.
• Patients with any form of Parkinsonism other than idiopathic PD or with a diagnosis of dementia or major psychiatric disorder. Individuals with mild to moderate depression will be sought for this study, unless their depressive disorder currently requires regular medical therapy.
• Patients who are on unacceptable prior/concomitant medications.
• Pregnant women
• Those who are not practicing effective birth control.
• Patients with prior bilateral neurosurgical intervention for the treatment of Parkinsonian symptoms, i.e. deep brain stimulation, pallidotomy, fetal tissue transplantation as well as patients at risk for symptomatic hypotension, cardiac arrhythmia, and/or myocardial ischemia secondary to intravenous levodopa challenge or NS2330 therapy.
• Patients who have taken an investigational drug within the last two months prior to randomization.
• Previous participation in any NS 2330 study.

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)

• 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

• 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

MeSH Terms

Conditions

Parkinson Disease; Dyskinesias

Interventions

Levodopa; Domperidone

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; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

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

Study Record Dates

• First Submitted: August 4, 2000
• First Posted: August 7, 2000
• Study Start: August 1, 2000
• Study Completion: July 1, 2003
• Last Updated: March 4, 2008

Record last verified: 2003-07

Locations

US (1)