Abstract Details

Title A Trial of Carbidopa for Vomiting Crises in Familial Dysautonomia

Topic Autonomic Disorders

Presentation(s) S37 - (-)

Poster/Presentation
Number 006

Background Patients with FD, an hereditary neuropathy that affects the development of sensory neurons of the baroreflex, are unable to restrain the release of catecholamines from sympathetic nerve terminals at times of stress. Recurrent attacks of nausea, retching and vomiting, associated with high levels of circulating dopamine are a disabling feature of the disease for which there is no effective treatment.

Objective

Design/Methods We enrolled 12 patients with FD in an open-label titration and treatment study to assess the safety of carbidopa, an inhibitor of the enzyme dopa decarboxylase that does not cross the blood brain barrier. We then conducted a randomized, double-blind, placebo-controlled, crossover study to evaluate its antiemetic efficacy.

Results All patients experienced severe cyclical nausea and uncontrollable retching that was refractory to standard treatments. Carbidopa at an average daily dose of 480 mg (range 325 to 600 mg/day) was well tolerated. In the double-blind phase, patients experienced significantly less nausea and retching while on carbidopa than on placebo (p<0.03 and p<0.02. respectively). Twenty-four hour urinary dopamine excretion was significantly lower while on carbidopa (147±32 ug/g crt) than while on placebo (222±41 ug/g crt, p<0.05).

Conclusions Carbidopa appears to be a safe and effective antiemetic in patients with FD likely by reducing the formation of dopamine outside the brain. Larger trials are warranted.

Authors/Disclosures
PRESENTER	No disclosure on file
Horacio C. Kaufmann, MD, FAAN (NYU Langone Health - NYU Dysautonomia Center)	Dr. Kaufmann has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Theravance. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly USA. Dr. Kaufmann has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda Pharmaceuticals. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ono Pharma UK Ltd. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vaxxinity. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Spinger. The institution of Dr. Kaufmann has received research support from Biogen. Dr. Kaufmann has received publishing royalties from a publication relating to health care.
	No disclosure on file
Felicia B. Axelrod, MD (New York University Medical Center)	No disclosure on file
Alastair Compston, PhD, FRCP	No disclosure on file

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