Augmenting Effects of L-DOPS With Carbidopa and Entacapone

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00547911
• Date of registration: 19/10/2007
• Prospective Registration: No
• Primary sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Public title: Augmenting Effects of L-DOPS With Carbidopa and Entacapone
• Scientific title: L-Dihydroxyphenylserine (L-DOPS) for Norepinephrine Deficiency: Interactions With Carbidopa and Entacapone
• Date of first enrolment: October 2007
• Target sample size: 14
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00547911
• Study type: Interventional
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: David S Goldstein, M.D.
• Affiliation: National Institute of Neurological Disorders and Stroke (NINDS)

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Multiple System Atrophy

Parkinson Disease

Autonomic Nervous System Diseases

Intervention(s)

Drug: Carbidopa

Drug: Entacapone

Drug: Droxidopa

Primary Outcome(s)

Plasma DHPG Concentrations After 400 mg of Droxidopa + 200 mg of Either Placebo, Carbidopa, or Entacapone [Time Frame: Up to 48 hours after receiving drug(s)]

Plasma Norepinephrine Concentrations After 400 mg of Droxidopa + 200 mg of Either Placebo, Carbidopa, or Entacapone [Time Frame: Up to 48 hours after receiving drug(s)]

Plasma DHMA Concentrations After 400 mg of Droxidopa + 200 mg of Either Placebo, Carbidopa, or Entacapone [Time Frame: Up to 48 hours after receiving drug(s)]

Plasma LDOPS Concentrations After 400 mg of Droxidopa + 200 mg of Either Placebo, Carbidopa, or Entacapone [Time Frame: Up to 48 hours after receiving drug(s)]

Secondary Outcome(s)

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)]

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)]

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)]

Secondary ID(s)

080012

08-N-0012

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 17/07/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00547911