Clinical Trial: Carbidopa for the Treatment of Nausea and Vomiting in Familial Dysautonomia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Carbidopa for the Treatment of Nausea and Vomiting in Familial Dysautonomia

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 t

Detailed Summary:

Patients with familial dysautonomia (FD), also called Riley Day syndrome or hereditary sensory and autonomic neuropathy type III, suffer recurrent attacks of uncontrollable nausea and vomiting that can last several hours or days and are severely disabling. Hypertension, tachycardia and skin blotching frequently accompany these attacks. Our long-term objective is to develop an effective treatment for nausea and vomiting in patients with FD.

In preliminary studies we found that plasma levels of dopamine were very high during attacks. Stimulation of dopamine receptors in the chemoreceptor trigger zone in the brainstem is a well-known cause of nausea and vomiting. The investigators postulate that acute increases in circulating dopamine levels are the cause of paroxysmal nausea and vomiting in FD.

Dopamine is synthesized by decarboxylation of the aminoacid L-dihydroxyphenylserine (L-DOPA) by the enzyme aromatic L-aminoacid decarboxylase, also known as DOPA decarboxylase. Patients with Parkinson's disease suffer nausea and vomiting when they receive treatment with L-DOPA. However, when L-DOPA is administered together with carbidopa, a reversible competitive inhibitor of DOPA decarboxylase that does not cross the blood brain barrier, nausea and vomiting are prevented. The investigators hypothesize that by blocking the conversion of DOPA to dopamine and thus preventing its increase in plasma, treatment with carbidopa will decrease nausea and vomiting in patients with FD.

Although carbidopa has been used for many years in patients with Parkinson's disease, it has never been used in patients with FD. The first specific aim of this proposal is to assess the safety and tolerability of carbidopa in patients with FD.

The second specific a
Sponsor: New York University School of Medicine

Current Primary Outcome:

• Composite Daily Score [ Time Frame: 4 weeks ]
  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).
• 24 Hour Dopamine Levels [ Time Frame: 4 weeks ]
  Assay of 24 hour dopamine level excretion in urine

Original Primary Outcome: Number of Adverse Events [ Time Frame: 4 months ]

Current Secondary Outcome: Number of Episodes of Daily Nausea [ Time Frame: 4 weeks ]

Original Secondary Outcome: Nausea Scores and Dopamine Levels [ Time Frame: 4 months ]

Information By: New York University School of Medicine

Dates:
Date Received: September 13, 2010
Date Started: December 2009
Date Completion:
Last Updated: March 7, 2016
Last Verified: March 2016