The Safety, Tolerability and Efficacy of Dronabinol, for the Treatment of Nausea and Vomiting in Familial Dysautonomia

The Safety , Tolerability and Efficacy of Dronabinol, a Synthetic Endocannabinoid Receptor Agonist, for the Treatment of Nausea and Vomiting in Patients With Familial Dysautonomia

This is a pilot clinical trial of dronabinol 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.

Study Overview

• Status: Withdrawn
• Conditions: Nausea; Vomiting; Familial Dysautonomia
• Intervention / Treatment: Drug: Dronabinol; Other: Placebo

Detailed Description

The purpose of this pilot study is to assess the safety, tolerability and efficacy of dronabinol 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 dronabinol in patients with FD using an open-label dose titration phase followed by 4-weeks of wash-out period. Part 2 will address the efficacy of dronabinol for the treatment of nausea in patients with FD using a randomized, placebo controlled, double blind, 12-week cross over design.

The first specific aim of this proposal is to assess the safety and tolerability of dronabinol in patients with FD. The second specific aim of this proposal is to determine whether stimulation of endocannabinoid receptors with dronabinol will improve recurrent nausea in patients with FD. Secondary aims are to determine whether stimulation of endocannabinoid receptors with dronabinol will increase weight, and decrease anxiety.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients aged 18-60.
2. Confirmed diagnosis of familial dysautonomia by genetic testing.
3. Symptoms of severe nausea.
4. Able to swallow the capsules.
5. Written informed consent or ascent to participate in the pilot trial and understanding that they can withdraw consent or accent at anytime without affecting their future care.
6. Ability to comply with the requirements of the study procedures, including taking blood pressure measurements at home

Exclusion Criteria:

1. Patients with a history of hypersensitivity to any cannabinoid or sesame oil.
2. Cannabinoid use in the previous 4 weeks (a urinary cannabinoid test will be performed before study entry).
3. Patients with a history of substance abuse, including alcohol abuse or dependence, or marijuana.
4. Seizure disorder with at least one epileptic seizure in the last 3 years or abnormal epileptic discharge in electroencephalography
5. Patients with history of bipolar disorder, severe depression or schizophrenia.
6. Patients that require driving, operating machinery, or engaging in hazardous activities.
7. Patients taking medications thought, in the investigator's opinion, to be unsafe when used with dronabinol.
8. Patients with atrial fibrillation, angina or an electrocardiogram documenting a significant abnormality that may jeopardize the patient's health.
9. Patients with significant pulmonary, liver, renal (creatinine > 2.0 mg/ml), or cardiac illness that may, in the investigators opinion jeopardize their health by participating in this pilot trial.
10. Patients with severe cognitive impairment or pervasive developmental disorders, or patients who are unable to clearly identify and rate their symptoms of nausea.
11. Women who are pregnant or lactating.
12. Patients who have a significant abnormality on clinical examination that may, in the investigator's opinion, jeopardize their health by participating in this pilot trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dranabinol Capsules; The initial dose will be 2.5 mg BID (5 mg/day), and the maximum dose will be 10 mg TID (30 mg/day).	Drug: Dronabinol; Other Names: Marinol
Placebo Comparator: Placebo Capsules; placebo	Other: Placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse effects	number of AEs during 4 weeks active drug phase vs. 4 weeks placebo phase	8 weeks
Change in nausea scores	nausea scores during 4 weeks active drug phase vs. 4 weeks placebo phase	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in weight.	change in weight (kgs) during 4 weeks active drug phase vs. 4 weeks placebo phase	8 weeks
Change in anxiety scores	change in anxiety scale scores during 4 weeks active drug phase vs. 4 weeks placebo	8 Weeks

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Horacio C Kaufmann, MD, NYU Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): March 22, 2019
• Study Completion (Actual): March 22, 2019

Study Registration Dates

• First Submitted: November 13, 2015
• First Submitted That Met QC Criteria: November 18, 2015
• First Posted (Estimate): November 20, 2015

Study Record Updates

• Last Update Posted (Actual): June 13, 2019
• Last Update Submitted That Met QC Criteria: June 11, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: delta-9-tetrahydrocannabinol (THC)
• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Signs and Symptoms, Digestive; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Hereditary Sensory and Autonomic Neuropathies; Nausea; Vomiting; Primary Dysautonomias; Autonomic Nervous System Diseases; Dysautonomia, Familial; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: 14-01577

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No