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

Study Overview
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Brief Summary
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This is a pilot open-label study to evaluate the feasibility of conducting a clinical trial using sublingual dexmedetomidine sublingual film to treat hyperadrenergic autonomic crises in patients with Familial Dysautonomia at home. The primary aims are to examine the feasibility of performing a clinical trial using dexmedetomidine at home to terminate autonomic crisis, and refine the interventions and assessments used to evaluate autonomic crisis termination.

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

Conditions
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Familial Dysautonomia

Intervention / Treatment
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* Drug: Dexmedetomidine Sublingual


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genetically confirmed diagnosis of Familial Dysautonomia. Evidence of autonomic crisis, previous treatment with IV dexmedetomidine without significant side effects, and registered medical data within the year preceding the study in our database. One or more autonomic crises during the last year. Age above 18 years. 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 potential: 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: a. Oxygen saturation less than 92% on room air or baseline need for oxygen, change from baseline oxygen dependency. b. Respiratory rate >20 breaths per minute. c. Supine blood pressure ≤ 90/60mmHg d. Febrile illness with temperature >100.3 F. e. 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. MoCA score <25 points.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sublingual dexmedetomidine<br>Participants will be administered two 60 micrograms sublingual films of IGLMI following start of an autonomic crises. The maximum amount for the study is four oral films of 60 micrograms in 24 hours, two at the beginning of the crises and if needed, two additional within two hours. | Drug: Dexmedetomidine Sublingual<br>* Dexmedetomidine 120 mcg on two thin dissolvable films for sublingual administration<br>* Other names: IGALMI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects screened per month |  | Month 6 | 
| Number of subjects enrolled per month |  | Month 6 | 
| Number of completed crises treated at home within the protocol |  | Month 6 | 
| Number of subjects that underwent an autonomic crisis per month |  | Month 6 | 
| Average duration of the study from visit 1 to the last visit of the last patient |  | From enrollment to end of treatment (up to 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of time from autonomic crisis onset to the initiation of the video recording |  | Up to 2 hours | 
| Length of time from autonomic crisis onset to administration of the medication |  | Up to 2 hours | 
| Length of time from autonomic crisis onset to crisis resolution |  | Up to 24 hours | 
| Length of time it took to complete assessments from start of autonomic crisis |  | Up to 24 hours | 
| Percentage of completion of all rating scales | The scales required to be completed is the Autonomic Crisis Symptom Assessment Scale (ACSAS), the study safety assessments and the Richmond Agitation-Sedation Scale. | Month 6 | 
| Change in blood pressure |  | Pre-dose, up to 2 hours post-dose | 
| Change in heart rate |  | Pre-dose, up to 2 hours post-dose | 
| Change in number of vomiting episodes |  | Pre-dose, up to 2 hours post-dose | 
| Change in number of retching episodes |  | Pre-dose, up to 2 hours post-dose |