Carbidopa for the Treatment of Nausea and Vomiting in Familial Dysautonomia
Condition: Familial Dysautonomia
MeSH terms: Primary Dysautonomias; Autonomic Nervous System Diseases; Dysautonomia, Familial; Vomiting
Intervention: Carbidopa; Placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Carbidopa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 12.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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