Clinical Trial: Augmenting Effects of L-DOPS With Carbidopa and Entacapone
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: L-Dihydroxyphenylserine (L-DOPS) for Norepinephrine Deficiency: Interactions With Carbidopa and Entacapone
Brief 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, includi
Detailed Summary:
Objective: L-DOPS is a synthetic chemical that can be converted to norepinephrine (NE). NE is a key messenger of the sympathetic nervous system. Failure of the sympathetic nervous system results in orthostatic hypotension (OH), a fall in blood pressure when the person stands up. Patients with Parkinson disease (PD) often have OH that is related to loss of sympathetic nerves and to NE deficiency. L-DOPS can help treat OH in these patients. Drugs used commonly to treat PD, however, probably influence effects of L-DOPS. Carbidopa, which combined with levodopa (brand name Sinemet) is a standard treatment for PD, might prevent L-DOPS from being turned into NE outside the brain and therefore interfere with effects of L-DOPS on blood pressure. Entacapone (brand name Comtan) might augment production of NE after a dose of L-DOPS, by decreasing metabolic breakdown of L-DOPS. The first goal of this study is to test these hypotheses in patients with neurogenic OH. NE is also a chemical messenger in the brain and is thought to participate in a variety of neuropsychiatric phenomena such as vigilance, mood, memory, and transmission of pain sensation. Patients with OH can have evidence of central NE deficiency. A second goal of this study is to determine whether depressed mood, apathy, fatigue, or pain improve with L-DOPS treatment in these patients. A third goal is to test whether carbidopa and entacapone, which both should enhance delivery of L-DOPS to the brain, augment L-DOPS effects on these symptoms. Finally, a fourth goal is to verify that carbidopa and entacapone augment neurochemical indices of central neural production of NE after a dose of L-DOPS.
Study Population: The subjects are patients with PD+NOH, MSA+NOH, or pure autonomic failure (PAF); and healthy volunteers. A total of 55 patients and 15 healthy volunteers are to be enrolled.
Original Primary Outcome: Concentrations of L-DOPS, norepinephrine, and other catecholamines and their metabolites
Current Secondary Outcome:
- Systolic Blood Pressures After 400 mg of Droxidopa + 200 mg of Either Placebo, Carbidopa, or Entacapone [ Time Frame: Up to 24 hours after receiving drug(s) ]Systolic blood pressure was assessed at baseline and after drug administration at 1 hour, 2 hours, 3 hours, 6 hours, and 24 hours.
- Diastolic Blood Pressures After 400 mg of Droxidopa + 200 mg of Either Placebo, Carbidopa, or Entacapone [ Time Frame: Up to 24 hours after receiving drug(s) ]Diastolic blood pressure was assessed at baseline and after drug administration at 1 hour, 2 hours, 3 hours, 6 hours, and 24 hours.
- Heart Rate After 400 mg of Droxidopa + 200 mg of Either Placebo, Carbidopa, or Entacapone [ Time Frame: Up to 24 hours after receiving drug(s) ]Heart rate was assessed at baseline and after drug administration at 1 hour, 2 hours, 3 hours, 6 hours, and 24 hours.
Original Secondary Outcome: Blood pressure and other hemodynamic measures, supine and upright
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: October 19, 2007
Date Started: October 2007
Date Completion:
Last Updated: June 17, 2014
Last Verified: June 2014
