Carbidopa for the Treatment of Nausea and Vomiting in Familial Dysautonomia
Status:
Completed
Trial end date:
2012-10-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 3
Details
Lead Sponsor:
New York University School of Medicine NYU Langone Health