Carbidopa for the Treatment of Excessive Blood Pressure Variability (CarbiFD)

NYU Langone Health

Status and phase

Completed

Phase 2

Conditions

Baroreflex Failure Syndrome

Dysautonomia, Familial

Treatments

Drug: Carbidopa High-Dose

Drug: Carbidopa Low-Dose

Other: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02553265

13-00065

FD-R-004772 (Other Grant/Funding Number)

Details and patient eligibility

About

The overall study objectives are to determine whether carbidopa (Lodosyn®) is safe and well tolerated and to assess whether it can inhibit catecholamine-induced paroxysmal hypertension and normalize or reduce the exaggerated blood pressure variability in patients with familial dysautonomia (FD, also called hereditary sensory and autonomic neuropathy type III or Riley-Day syndrome). Funding Source- FDA OOPD.

Full description

The investigators propose to perform a double-blind randomized trial with a cross over design to compare high dose (600 mg/day) and low dose (300 mg per day) carbidopa blockade with placebo. Patients will be randomly assigned to a high-dose/low-dose/placebo sequence, lowdose/placebo/high-dose sequence or placebo/high-dose/low-dose sequence. Participants will remain on each treatment period for 28-days.

Aim 1: To evaluate the safety and tolerability of carbidopa in FD patients with particular emphasis on the orthostatic fall in blood pressure.

Aim 2: As proof of concept, examine the hemodynamic effects of carbidopa and determine its effects on norepinephrine production, BP variability and paroxysmal hypertension.

Aim 3: In a dose finding study, compare the effects of low (300 mg/day) and high (600 mg/day) dose carbidopa blockade vs. placebo on BP variability and paroxysmal hypertension.

Enrollment

22 patients

Sex

All

Ages

10 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female patients with familial dysautonomia (FD) age 10 or older
Unstable blood pressure, defined as:
- Systolic BP standard deviation >15 mmHg
- Or coefficient of variation >15%
- Or documented episodic hypertensive peaks (>140mmHg)
Confirmed diagnosis of FD (genetic testing)
Providing written informed consent (or ascent) to participate in the trial
Ability to comply with the requirements of the study procedures.

Exclusion criteria

Patients taking monoamine oxidase (MAO)-inhibitors
Patients taking: metoclopramide, domperidone, risperidone or other dopamine blockers
Patients taking tricyclic antidepressants
Patients taking neuroleptic drugs (haloperidol and chlorpromazine)
Patients with a known hypersensitivity to any component of this drug.
Patients with atrial fibrillation, angina or significant ECG abnormality
Patients with significant pulmonary, cardiac, liver, renal (creatinine >2.0 mg/ml)
Patients who have a significant abnormality on clinical examination that may, in the investigator's opinion might jeopardize their healthy participating in this trial.
Women who are pregnant or lactating.