Carbidopa for the Treatment of Nausea and Vomiting in Familial Dysautonomia

NCT01212484 | Completed Phase 3 Results

• 1 other identifier: 09-0011
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a pilot clinical trial of carbidopa to treat disabling attacks of nausea and vomiting in patients with familial dysautonomia (FD, also known as Riley Day syndrome or hereditary sensory and autonomic neuropathy type III). FD is a rare autosomal recessive disease in which the growth and development of selective nerves is impaired. Patients with FD suffer recurrent uncontrollable nausea and vomiting crises accompanied by skin flushing, tachycardia and arterial hypertension. Current treatments of nausea are ineffective or have intolerable side sides. Our long-term goal is to treat nausea effectively and without side effects, a therapeutic intervention that would markedly improve the quality of life of patients with FD. The investigators have recently found that resting plasma dopamine levels are high in patients with FD and increase up to 40-fold during nausea and vomiting attacks. This led us to postulate that stimulation of dopamine receptors in the chemoreceptor trigger zone of the brainstem is the likely mechanism of vomiting. Carbidopa is a reversible competitive inhibitor of aromatic L-amino acid decarboxylase (also known as dopa-decarboxylase) that cannot cross the blood brain barrier. It has been used successfully for many years to block the extracerebral synthesis of dopamine and avoid nausea and vomiting in patients with Parkinson's disease taking levodopa. The investigators reasoned that carbidopa could have a similar antiemetic effect in patients with FD. The investigators propose to conduct a pilot trial to assess the safety, tolerability and efficacy of carbidopa for the treatment of nausea in patients with FD. The pilot trial will recruit 25 patients with FD who complain of severe nausea that affects their quality of life. The trial will be divided into two consecutive, but independent parts. Part 1, will address the safety and tolerability of carbidopa in patients with FD using an open-label dose titration phase followed by 4-weeks of open-label treatment. Part 2, will address the efficacy of carbidopa for the treatment of nausea in patients with FD using a randomized, placebo controlled, double blind, 4-week cross over design. The investigators hope to demonstrate that carbidopa is a safe, well-tolerated drug that blocks the peripheral formation of dopamine and thus prevents dopamine-induced nausea and vomiting attacks in patients with FD.

Conditions

Familial Dysautonomia

Outcome Measures

Primary Outcomes (2)

• Composite Daily Score

  Daily scores were reported on a modified version of the Rhodes Index of Nausea, Vomiting and Retching, which included all 5 items relating to nausea and retching. Items addressing vomiting/throwing up were omitted, as all participants had antireflux surgery that prevented vomiting (Nissen fundoplication). Retching distress, nausea distress, number of nausea episodes per day, number of retching episodes per day, and the amount of time spent feeling nauseous were graded on a 5-point scale. Scores range from 0 (no nausea/distress) to 20 (most nausea/distress).

  4 weeks

• 24 Hour Dopamine Levels

  Assay of 24 hour dopamine level excretion in urine

  4 weeks

Secondary Outcomes (1)

• Number of Episodes of Daily Nausea

  4 weeks

Study Arms (2)

Placebo (first), Carbidopa (second)

EXPERIMENTAL

Crossover design Placebo first followed by carbidopa

Drug: Carbidopa; Drug: Placebo

Carbidopa (first), Placebo (second)

EXPERIMENTAL

Crossover design carbidopa first followed by placebo

Drug: Carbidopa; Drug: Placebo

Interventions

Carbidopa DRUG

The trial will be divided into two consecutive, but independent parts. Phase 1, will address the safety and tolerability of carbidopa in patients with FD using an open-label dose titration phase followed by 4-weeks of open-label treatment. Phase 2, will address the efficacy of carbidopa for the treatment of nausea in patients with FD using a randomized, placebo controlled, double blind, 4-week cross over design.

Also known as: Lodosyn

Carbidopa (first), Placebo (second); Placebo (first), Carbidopa (second)

Placebo DRUG

The trial will be divided into two consecutive, but independent parts. Phase 1, will address the safety and tolerability of carbidopa in patients with FD using an open-label dose titration phase followed by 4-weeks of open-label treatment. Phase 2, will address the efficacy of carbidopa for the treatment of nausea in patients with FD using a randomized, placebo controlled, double blind, 4-week cross over design.

Carbidopa (first), Placebo (second); Placebo (first), Carbidopa (second)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male of female patients aged 12 and older
• Confirmed diagnosis of familial dysautonomia by genetic testing.
• Symptoms of severe nausea
• Written informed consent or ascent to participate in the pilot trial and understanding that they can withdraw consent at anytime without affecting their future care.
• Ability to comply with the requirements of the study procedures, including taking blood pressure measurements at home.

You may not qualify if:

• Patients taking metroclopromide, domperidone, risperidone or other dopamine blockers
• Patients taking MAO-inhibitors
• 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 an electrocardiogram documenting significant abnormality that may jeopardize the patient's health.
• Patients with significant pulmonary, liver, renal (creatinine \>2.0 mg/ml) or cardiac illness
• Patients who are unable to clearly identify and rate their symptoms of nausea.
• Women who are pregnant or lactating
• Patients who have a significant abnormality on clinical examination that may, in

Sponsors & Collaborators

• NYU Langone Health: lead

MeSH Terms

Conditions

Dysautonomia, Familial

Interventions

Carbidopa

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hereditary Sensory and Autonomic Neuropathies; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Methyldopa; Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Hydrazines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Horacio Kaufmann, MD; director of Dysautonomia Center
• Organization: NYU Medical Center

horacio.kaufmann@nyumc.org

212 263 7225

Study Officials

• Horacio C Kaufmann, M.D.

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2010
• First Posted: September 30, 2010
• Study Start: December 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: October 1, 2012
• Last Updated: March 28, 2016
• Results First Posted: March 28, 2016

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share