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

Phase 2
Conditions
Familial Dysautonomia
Interventions
Drug: Matching placebo
Registration Number
NCT06148311
Lead Sponsor
NYU Langone Health
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

Detailed Description

Not available

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
15
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sublingual dexmedetomidineDexmedetomidineParticipants 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.
Matching Sublingual PlaceboMatching placeboParticipants 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.
Primary Outcome Measures
NameTimeMethod
Percentage of patients with reduction of Autonomic crisis severity assessment scores (ACSAS) to ≤ 5 pointsUp 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 pressureUp 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 rateUp 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 episodesUp 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
NameTimeMethod
Percentage of patients with ≥ 20% reduction in hospitalizationsUp 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 durationUp to 48 months

Study team will compare historical data to number of days during hospital stay that occurred after taking one or more doses.

Change in number of medical complicationsBaseline, up to 48 months

Study team will compare historical data to number of medical complications of hospitalizations occurred after taking one or more doses.

Percentage of patients with ≥ 30% reduction in ICU stay durationUp to 48 months

Study team will compare historical data to number of days at the ICU that occurred after taking one or more doses.

Trial Locations

Locations (1)

NYU Langone Health

🇺🇸

New York, New York, United States

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