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

NYU Langone Health

Status and phase: Invitation-only; Phase 2

Conditions: Familial Dysautonomia

Treatments: Drug: Dexmedetomidine; Drug: Matching placebo

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT06148311

1R01FD007826-01 (U.S. FDA Grant/Contract)

22-01332

Details and patient eligibility

About

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

Enrollment: 15 estimated patients

Sex: All

Ages: 16 to 80 years old

Volunteers: No 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:

  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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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15 participants in 2 patient groups, including a placebo group

Sublingual dexmedetomidine

Experimental group

Description:

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.

Treatment:

Drug: Dexmedetomidine

Matching Sublingual Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Matching placebo