Dexmedetomidine Sublingual Film for the Ambulatory Treatment of Hyperadrenergic Autonomic Crisis in Patients With Familial Dysautonomia

The purpose of this placebo controlled interventional study is to collect preliminary data on administering dexmedetomidine in patients with Familial Dysautonomia (FD) during a rapid cessation of autonomic crisis. The primary aims are to assess the feasibility and evaluate if measurements of heart rate, blood pressure and oxygen saturation can predict the start of an autonomic crisis.

Funding Source- FDA OOPD

Study Overview

• Status: Enrolling by invitation
• Conditions: Familial Dysautonomia
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Matching placebo

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Genetically confirmed diagnosis of Familial Dysautonomia.
• One or more autonomic crises during the last year.
• Our database shows evidence of autonomic crisis, previous treatment with IV dexmedetomidine, and registered medical data within the year preceding the study.
• Age 16 years or older
• The patient has a responsible caretaker to communicate with the medical providers.
• Provision of signed and dated informed consent form from the patient and responsible caregiver
• Able to state willingness to comply with all study procedures and availability for the duration of the study
• For males and females of reproductive age: use condoms for contraception if sexually active.

Exclusion Criteria:

• At the consideration of the principal investigator, the caregiver cannot fully understand the protocol, or communicate during the crisis with the Center.

• The patient during the crisis, before taking the medication, has any of the following:

  1. Oxygen saturation less than 92% on room air or baseline need for oxygen, change from baseline oxygen dependency.
  2. Respiratory rate >25 breaths per minute.
  3. Supine blood pressure ≤ 90/860mmHg
  4. Febrile illness with temperature >100.3 F.
  5. Serological signs of infection (WBC count >10 g/dL, or CRP >10 mg/L or ESR>20, or above their steady historical baseline levels) in recent (less than one month) studies.
• The patient is a female and has a positive pregnancy test.
• The Montreal Cognitive Exam (MoCA) is below 25 points.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sublingual dexmedetomidine; Participants will be administered 120 micrograms sublingual film following start of an autonomic crisis. In case the crisis has not subsided after 2 hours, the patient will be instructed to take the second dose. The maximum amount for the study is two oral films within two hours for each episode but not more than 24 hours apart, one at the beginning of the crisis and if needed, one additional within two hours.	Drug: Dexmedetomidine; Dexmedetomidine 120 mcg will be given under the tongue on a thin dissolvable film.
Placebo Comparator: Matching Sublingual Placebo; Participants will be administered the matching placebo sublingual film following start of an autonomic crisis. In case the crisis has not subsided after 2 hours, the patient will be instructed to take the second dose. The maximum amount for the study is two oral films within two hours for each episode but not more than 24 hours apart, one at the beginning of the crisis and if needed, one additional within two hours.	Drug: Matching placebo; One matching placebo will be given under the tongue on a thin dissolvable film.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with reduction of Autonomic crisis severity assessment scores (ACSAS) to ≤ 5 points	ACSAS tool will be used to measure objectively and record signs and symptoms of autonomic crisis, which includes documentation of blood pressure, heart rate, skin flushing and blotching, sweating, and behavioral changes. Scores are totaled at each timepoint (0 minutes, 15 min., 45 min., 1.5 hours, 2hr.) ranging from 0 (Normal) to 16 (most severe symptoms occurred).	Up to 2 hours post administration
Percentage of patients with 25% reduction in blood pressure	Patients will be monitored with a hospital-at-home (H@H) device to allow visualization of vital signs in real life. The H@H monitor (Biobeat™) is an FDA approved device and will be attached to the patient´s chest by an adhesive patch which will transmit blood pressure. Blood pressure will be monitored before taking each dose and up to 2 hours after.	Up to 2 hours post administration
Percentage of patients with >20% reduction in heart rate	Patients will be monitored with a hospital-at-home (H@H) device to allow visualization of vital signs in real life. The H@H monitor (Biobeat™) is an FDA approved device and will be attached to the patient´s chest by an adhesive patch which will transmit heart rate. Heart rate will be monitored before taking each dose and up to 2 hours after.	Up to 2 hours post administration
Percentage of patients with >50% reduction in vomiting/retching episodes	Patients will be monitored by their care givers for of episodes of vomiting/ retching before taking each dose and up to 2 hours after.	Up to 2 hours post administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with ≥ 20% reduction in hospitalizations	Study team will compare historical data to number of hospitalizations occurred after taking one or more doses.	Up to 48 months
Percentage of patients with ≥ 20% reduction in hospital stay duration	Study team will compare historical data to number of days during hospital stay that occurred after taking one or more doses.	Up to 48 months
Percentage of patients with ≥ 30% reduction in ICU stay duration	Study team will compare historical data to number of days at the ICU that occurred after taking one or more doses.	Up to 48 months
Change in number of medical complications	Study team will compare historical data to number of medical complications of hospitalizations occurred after taking one or more doses.	Baseline, up to 48 months

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Alejandra Gonzalez-Duarte, MD, NYU Langone Health, NYU Dysautonomia Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: November 20, 2023
• First Submitted That Met QC Criteria: November 20, 2023
• First Posted (Actual): November 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Familial Dysautonomia; Hereditary Sensory and Autonomic Neuropathy type 3; HSAN; autonomic sympathetic crises
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Primary Dysautonomias; Autonomic Nervous System Diseases; Polyneuropathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dysautonomia, Familial; Hereditary Sensory and Autonomic Neuropathies; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Dexmedetomidine
• Other Study ID Numbers: 22-01332; 1R01FD007826-01 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Alejandra.gonzalez-duarte@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will be provided access upon reasonable request. Requests should be directed to Alejandra.gonzalez-duarte@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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