Carbidopa for the Treatment of Excessive Blood Pressure Variability

NCT ID: NCT02553265

Last Updated: 2022-02-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-09-30

Study Completion Date

2019-05-10

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Dysautonomia, Familial Baroreflex Failure Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Matching placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Low-Dose Carbidopa

Group Type EXPERIMENTAL

Carbidopa Low-Dose

Intervention Type DRUG

300 mg/day

High-Dose Carbidopa

Group Type ACTIVE_COMPARATOR

Carbidopa High-Dose

Intervention Type DRUG

600 mg/day

Interventions

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Carbidopa Low-Dose

300 mg/day

Intervention Type DRUG

Placebo

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

Intervention Type OTHER

Carbidopa High-Dose

600 mg/day

Intervention Type DRUG

Other Intervention Names

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Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486 Placebo control pill Lodosyn ®, DL-α-methyl-α-hydrazino-3, 4-dihydroxyphenyl-propionic acid, HMD, MK-486

Eligibility Criteria

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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.
Minimum Eligible Age

10 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NYU Langone Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Horacio C Kaufmann, MD

Role: PRINCIPAL_INVESTIGATOR

NYU School of Medicine

Lucy J Norcliffe-Kaufmann, PhD

Role: PRINCIPAL_INVESTIGATOR

NYU School of Medicine

Locations

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NYU Langone Medical Center, Dyautonomia Center, Suite 9Q

New York, New York, United States

Site Status

NYU Medical Center

New York, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 23553478 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22739220 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22129610 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22045363 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21098405 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25323828 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://med.nyu.edu/neurology/dysautonomia-center

New York University (NYU) Dysautonomia Center Research Site

http://nyulangone.org/conditions/familial-dysautonomia

Familial dysautonomia medical information

http://familialdysautonomia.org/

Patient Advocacy Group

Other Identifiers

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FD-R-004772

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

13-00065

Identifier Type: -

Identifier Source: org_study_id

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