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

NCT06148311 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 2 other identifiers: 22-013321R01FD007826-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Familial Dysautonomia

Keywords

Familial Dysautonomia; Hereditary Sensory and Autonomic Neuropathy type 3; HSAN; autonomic sympathetic crises

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• Percentage of patients with ≥ 20% reduction in hospitalizations

  Up to 48 months

• Percentage of patients with ≥ 20% reduction in hospital stay duration

  Up to 48 months

• Percentage of patients with ≥ 30% reduction in ICU stay duration

  Up to 48 months

• Change in number of medical complications

  Baseline, up to 48 months

Study Arms (2)

Sublingual dexmedetomidine

EXPERIMENTAL

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

Matching Sublingual Placebo

PLACEBO COMPARATOR

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

Interventions

Matching placebo DRUG

One matching placebo will be given under the tongue on a thin dissolvable film.

Matching Sublingual Placebo

Dexmedetomidine DRUG

Dexmedetomidine 120 mcg will be given under the tongue on a thin dissolvable film.

Sublingual dexmedetomidine

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Oxygen saturation less than 92% on room air or baseline need for oxygen, change from baseline oxygen dependency.
• Respiratory rate \>25 breaths per minute.
• Supine blood pressure ≤ 90/860mmHg
• Febrile illness with temperature \>100.3 F.
• 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.

Sponsors & Collaborators

• NYU Langone Health: lead
• Food and Drug Administration (FDA): collaborator

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Dysautonomia, Familial; Hereditary Sensory and Autonomic Neuropathies

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Alejandra Gonzalez-Duarte, MD

  NYU Langone Health, NYU Dysautonomia Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2023
• First Posted: November 28, 2023
• Study Start: July 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

US (1)