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

Sponsor

NYU Langone Health (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06148311

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Familial Dysautonomia	Drug: Matching placebo Drug: Dexmedetomidine	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Feb 1, 2024

Anticipated Primary Completion Date :

Jan 1, 2027

Anticipated Study Completion Date :

Sep 1, 2027

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Percentage of patients with reduction of Autonomic crisis severity assessment scores (ACSAS) to ≤ 5 points [Up to 2 hours post administration]
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).
Percentage of patients with 25% reduction in blood pressure [Up to 2 hours post administration]
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.
Percentage of patients with >20% reduction in heart rate [Up to 2 hours post administration]
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.
Percentage of patients with >50% reduction in vomiting/retching episodes [Up to 2 hours post administration]
Patients will be monitored by their care givers for of episodes of vomiting/ retching before taking each dose and up to 2 hours after.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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.