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Dysautonomia, FamilialPhase 2CarbiFDNCT02553265

Carbidopa for the Treatment of Excessive Blood Pressure Variability

A Phase 2 study testing Carbidopa Low-Dose and Carbidopa High-Dose in people with Dysautonomia, Familial and Baroreflex Failure Syndrome, run by NYU Langone Health at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 10 to 60 years
What is being tested?
Carbidopa Low-Dose and Carbidopa High-Dose
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
22 participants
Where
2 sitesUnited States
Study dates
Sep 2015to 10 May 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 9Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • NYU Langone Medical Center, Dyautonomia Center, Suite 9Q

    New York, New York, 10016

  • NYU Medical Center

    New York, New York, 10016

Other trials in United States

About this study

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

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.

Read the detailed 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.

Being tested
Carbidopa Low-Dose, Placebo, Carbidopa High-Dose
Keywords
Familial dysautonomia (HSAN III), Norepinephrine, Sympathetic nervous system, Autonomic nervous system, Blood pressure variability, Hypertension, Carbidopa/Lodosyn, Afferent baroreflex failure, Clinical trial
Medical subject headings
Dysautonomia, Familial, Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Carbidopa Low-DoseDrug

    Also called Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486

    300 mg/day

  • PlaceboOther

    Also called Placebo control pill

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

  • Carbidopa High-DoseDrug

    Also called Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486

    600 mg/day

Study groups in NCT02553265
Study groupRoleWhat they receive
PlaceboPlacebo comparatorMatching placebo
Receives: Other: Placebo
Low-Dose CarbidopaExperimentalNot described
Receives: Drug: Carbidopa Low-Dose
High-Dose CarbidopaActive comparatorNot described
Receives: Drug: Carbidopa High-Dose

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: Up to 90 days

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

    Body mass measured in kg

    Measured: Up to 90 days

  3. Number of Participants With Abnormal Electrocardiographic Interval Patterns

    Clinically significant changes in the intervals of characteristic electrocardiographic patterns

    Measured: Up to 90 days

  4. Average Systolic Blood Pressure Variability (Daytime)

    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

    Measured: up to Week 14

  5. Highest Systolic Blood Pressure

    Maximum blood pressure captured on 24-h ambulatory monitoring

    Measured: Day 1 of treatment period

  6. Systolic Blood Pressure

    SBP measured in the seated position

    Measured: up to Week 14

  7. Heart Rate

    Heart rate in the seated position

    Measured: up to Week 14

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

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

    Measured: Up to 90 days

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

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

    Measured: Up to 90 days

Secondary outcomes (6)
  1. Severity of Hypotension During an Active Stand Test

    Lowest blood pressure captured during 3 minutes of standing

    Measured: up to Week 14

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

    Measured: Up to 90 days

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

    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.

    Measured: Up to 90 Days

  4. 24-h Urinary Norepinephrine Excretion

    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.

    Measured: up to Week 14

  5. Coefficient of Systolic BP Variability (Daytime)

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

    Measured: up to Week 14

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

    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

    Measured: up to Week 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2015 (estimated)
  2. Study startSep 2015
  3. Primary completion10 May 2019
  4. Study completion10 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02553265
Sponsor's protocol ID
13-00065
Other IDs
FD-R-004772
Acronym
CarbiFD
Status last verified
Jan 2022
First submitted
14 Sep 2015
Last updated
9 Feb 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Norcliffe-Kaufmann L, Martinez J, Axelrod F, Kaufmann H. Hyperdopaminergic crises in familial dysautonomia: a randomized trial of carbidopa. Neurology. 2013 Apr 23;80(17):1611-7. doi: 10.1212/WNL.0b013e31828f18f0. Epub 2013 Apr 3.

    PubMed 23553478
  • Norcliffe-Kaufmann LJ, Axelrod FB, Kaufmann H. Cyclic vomiting associated with excessive dopamine in Riley-day syndrome. J Clin Gastroenterol. 2013 Feb;47(2):136-8. doi: 10.1097/MCG.0b013e3182582cbf.

    PubMed 22739220
  • Norcliffe-Kaufmann L, Axelrod FB, Kaufmann H. Developmental abnormalities, blood pressure variability and renal disease in Riley Day syndrome. J Hum Hypertens. 2013 Jan;27(1):51-5. doi: 10.1038/jhh.2011.107. Epub 2011 Dec 1.

    PubMed 22129610
  • Kaufmann H, Malamut R, Norcliffe-Kaufmann L, Rosa K, Freeman R. The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale. Clin Auton Res. 2012 Apr;22(2):79-90. doi: 10.1007/s10286-011-0146-2. Epub 2011 Nov 2.

    PubMed 22045363
  • Norcliffe-Kaufmann L, Axelrod F, Kaufmann H. Afferent baroreflex failure in familial dysautonomia. Neurology. 2010 Nov 23;75(21):1904-11. doi: 10.1212/WNL.0b013e3181feb283.

    PubMed 21098405
  • Palma JA, Norcliffe-Kaufmann L, Fuente-Mora C, Percival L, Mendoza-Santiesteban C, Kaufmann H. Current treatments in familial dysautonomia. Expert Opin Pharmacother. 2014 Dec;15(18):2653-71. doi: 10.1517/14656566.2014.970530. Epub 2014 Oct 17.

    PubMed 25323828

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carbidopa Low-Dose and Carbidopa High-Dose in people with Dysautonomia, Familial and Baroreflex Failure Syndrome, run by NYU Langone Health at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Reported Adverse Events Related to Study Drug (time frame: Up to 90 days). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02553265, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2022; AzTrials last refreshed its copy on 8 Nov 2026.

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