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Completed

NCT Number: NCT02553265

Carbidopa for the Treatment of Excessive Blood Pressure Variability

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.

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Key information

Conditions

Dysautonomia, Familial Autonomic Nervous System Diseases Baroreflex Failure Syndrome Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hereditary Sensory and Autonomic Neuropathies Heredodegenerative Disorders, Nervous System Hypertension Nervous System Diseases Nervous System Malformations Neurodegenerative Diseases Neuromuscular Diseases Peripheral Nervous System Diseases Polyneuropathies Primary Dysautonomias Vascular Diseases

Age range

10 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

NYU Langone Medical Center, Dyautonomia Center, Suite 9Q, New York, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Carbidopa Low-Dose

Drug

300 mg/day

Other names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486

Placebo

Other

A placebo containing an inert substance, in capsule form that does not contain an active drug ingredient.

Other names: Placebo control pill

Carbidopa High-Dose

Drug

600 mg/day

Other names: Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486

Primary outcomes

  1. Number of Participants Who Reported Adverse Events Related to Study Drug

    Time frame: Up to 90 days

    Adverse events defined as: a change in a patient's baseline condition including intercurrent illnesses irrespective of the relationship to carbidopa treatment. This will be monitored primarily with phone calls at weekly intervals. In addition, patients will be asked about adverse events while at the office. Patients will also fill a daily diary with a specific prompts to note any adverse events.

  2. Number of Participants With Significant Changes in Body Mass That Resulted in Discontinuation From the Study.

    Time frame: Up to 90 days

    Body mass measured in kg

  3. Number of Participants With Abnormal Electrocardiographic Interval Patterns

    Time frame: Up to 90 days

    Clinically significant changes in the intervals of characteristic electrocardiographic patterns

  4. Average Systolic Blood Pressure Variability (Daytime)

    Time frame: up to Week 14

    Patients with FD undergo ambulatory BP monitoring while keeping a detailed log of their activities (sleep/meal-times/medications/posture/symptoms). Variability in blood pressure overtime will be measured by the standard deviation during awake hours

  5. Highest Systolic Blood Pressure

    Time frame: Day 1 of treatment period

    Maximum blood pressure captured on 24-h ambulatory monitoring

  6. Systolic Blood Pressure

    Time frame: up to Week 14

    SBP measured in the seated position

  7. Heart Rate

    Time frame: up to Week 14

    Heart rate in the seated position

  8. Number of Participants Who Displayed Clinical Significant Laboratory Values on CBC or Metabolic Panel

    Time frame: Up to 90 days

    Clinically significant laboratory values include complete blood count (CMC) and metabolic panel related to treatment with carbidopa

  9. Number of Participants Who Displayed Clinically Significant Values in Urine Safety Parameters

    Time frame: Up to 90 days

    Clinically significant values on urinalysis, urine safety parameters related to treatment with carbidopa

Secondary outcomes

  1. Severity of Hypotension During an Active Stand Test

    Time frame: up to Week 14

    Lowest blood pressure captured during 3 minutes of standing

  2. Number of Participants Who Reported Worsening of OH Symptoms or Dropped Out Because of Worsening OH While on Active Study Drug

    Time frame: Up to 90 days

  3. Frequency of Worsening Symptoms Noted in the Patient's Diary

    Time frame: Up to 90 Days

    A tailored questionnaire to examine symptoms over the treatment period and the used of as needed medications. Each day will have a designated page. Since nausea/vomiting and hypertension occur together in FD we will use a diary consisting of a simplified version of the Rhodes Index 44 symptoms of nausea/retching, with items addressing vomiting/throwing up omitted, as most participants will have had anti-reflux surgery to prevent vomiting (fundoplication), graded on a 5-point scale (appendix 2). The diary will also include space to write down any adverse events on a daily basis.

  4. 24-h Urinary Norepinephrine Excretion

    Time frame: up to Week 14

    Norepinephrine concentration determined from a 24-hour urine sample in a bottle shielded from light containing preservative. Patients will be instructed to refrigerate their sample and bring it on the morning of their visit in a cool bag.

  5. Coefficient of Systolic BP Variability (Daytime)

    Time frame: up to Week 14

    The measurement of blood pressure variability based on the standard deviation that also takes into account the underlying level of BP.

  6. Morning Surge in Systolic BP on Awakening From Sleep (24-h)

    Time frame: up to Week 14

    The morning surge will be calculated as the difference between the mean systolic blood pressure during the hour that included the lowest blood pressure during sleep and maximum value detected within 2-h of awakening from sleep

Sponsors and collaborators

Lead sponsor

NYU Langone Health

Other

Registry information

Official study title

Carbidopa in Familial Dysautonomia: Phase-II Study, Investigational New Drug (IND) 117435, Date: 01/07/13

Acronym: CarbiFD

Important dates

Study start
2015
Primary completion
2019
Study completion
2019
First posted
Sep 17, 2015
Registry last updated
Feb 9, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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