Augmenting Effects of L-DOPS With Carbidopa and Entacapone

• Status: Terminated
• Trial end date: 2013-04-01
• Target enrollment: 0
• Participant gender: All

Summary

An experimental drug called L-DOPS increases production in the body of a messenger chemical called norepinephrine. Cells in the brain that make norepinephrine are often gone in Parkinson disease. The exact consequences of this loss are unknown, but they may be related to symptoms such as fatigue, depression, or decreased attention that occur commonly in Parkinson disease. This study will explore effects of L-DOPS in conjunction with carbidopa and entacapone, which are drugs used to treat Parkinson disease. We wish to find out what the effects are of increasing norepinephrine production in the brain and whether carbidopa and entacapone augment those effects.

Volunteers for this study must be at least 18 years of age and able to give consent to participate in the study. To participate in the study, volunteers must discontinue use of alcohol, tobacco, and certain herbal medicines or dietary supplements, and must also taper or discontinue certain kinds of medications that might interfere with the results of the study. Candidates will be screened with a medical history and physical exam.

Participants will be admitted to the National Institutes of Health Clinical Center for two weeks of testing. The study will have three testing phases in a randomly chosen order for each participant:

• Single dose of L-DOPS

• Single dose of L-DOPS in conjunction with carbidopa

• Single dose of L-DOPS in conjunction with entacapone

Each phase will last two days, with a washout day between each phase in which no drugs will be given and no testing will be performed. In each phase, participants will undergo a series of tests and measurements, including blood pressure and electrocardiogram tests. Participants who are healthy volunteers will also have blood drawn and will undergo a lumbar puncture (also known as a spinal tap) to obtain spinal fluid for chemical tests.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Treatments: Carbidopa; Droxidopa; Entacapone; Norepinephrine

Criteria

• INCLUSION CRITERIA:

All subjects in this Protocol will have already undergone clinical laboratory evaluations called for in Clinical Protocol 03-N-0004, "Clinical Laboratory Evaluation of Primary Chronic Autonomic Failure.

EXCLUSION CRITERIA:

Age: People younger than 18 years old are excluded.

Risk: A candidate subject is excluded if, in the judgment of the Principal Investigator or Clinical Director, Protocol participation would place the subject at substantially increased acute medical risk. This includes the risks associated with air travel to the NIH. A candidate subject is excluded if, in the opinion of the Principal Investigator or Clinical Director, the medical risk outweighs the potential scientific benefit.

Disqualifying Conditions: A candidate subject is excluded if there is a disqualifying condition. Examples of disqualifying conditions are hepatic or renal failure, symptomatic congestive heart failure, severe anemia, psychosis, refractory ventricular arrhythmias, and symptomatic coronary heart disease. Persons with dementia interfering with their ability to provide informed consent are excluded. If dementia is suspected, such as by score on the mini-mental examination of less than 24, then a bioethics consult will be obtained.

Medications: A candidate subject is excluded if clinical considerations require that the patient continue treatment with a drug likely to interfere with the scientific results. Examples would be treatment with levodopa/carbidopa or a tricyclic antidepressant. Patients with known or suspected allergy or hypersensitivity to any test drug are excluded. Patients unable to discontinue nicotine or alcohol temporarily are excluded. Patients are not to discontinue any medications before the patient or the patient s doctor discusses this with Dr. Goldstein, the Principal Investigator, or Sandra Pechnik, the Research Nurse. If it is decided that discontinuing medications would be unsafe, then the patient is excluded from the study. Subjects must discontinue use of alcohol and tobacco throughout the period of testing. PD patients who have difficulty tolerating withdrawal of levodopa/carbidopa treatment may be treated with a dopamine receptor agonist during the study, with the dosing remaining the same.

Tricyclic antidepressants, drugs that inhibit L-aromatic-amino-acid decarboxylase or catechol-O-methyltransferase, levodopa, and carbidopa will be withdrawn throughout the period of study. Withdrawal of antiparkinsonian medications may worsen rigidity, bradykinesia, or tremor. These effects are not thought to adversely influence the long-term course of the disease. Withdrawal of tricyclic antidepressants may worsen depression. Drug withdrawal will be done only in inpatients. Alternative drugs, such as serotonin reuptake blockers, anti-anxiety agents, or dopamine receptor agonists, may be used at constant doses during the study.

Herbal Medicines and Dietary Supplements: Certain herbal medicines or dietary supplements are known or suspected to interfere with the experimental results, and such herbal medicines or dietary supplements must be discontinued before enrollment in the study. For many herbal medicines or dietary supplements, the mechanisms of action and therefore the possible effects on the experimental results are unknown. In cases where the subjects wish to continue their herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subjects may participate.

Practical Limitations: Subjects in whom we feel it would be difficult to insert a catheter into a vein are excluded. Subjects who are not expected clinically to tolerate lying still supine during the testing are excluded.

Pregnancy: Pregnant or lactating women are excluded. Women of childbearing potential must have a negative urine or blood test for pregnancy done within 24 hours before any testing involving radioactivity or an experimental drug.

Post-Lumbar Puncture Headache: Candidate Healthy Volunteers are excluded if they had a headache requiring a blood patch after lumbar puncture under fluoroscopic guidance.