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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Familial Dysautonomia
• Intervention / Treatment: Drug: Dexmedetomidine Sublingual

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alejandra Gonzalez-Duarte, MD; Phone Number: 2122637225; Email: Alejandra.gonzalez-duarte@nyulangone.org
• Study Contact Backup: Name: Horacio Kaufmann, MD; Phone Number: 2122637225; Email: Horacio.kafumann@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sublingual dexmedetomidine; 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; Dexmedetomidine 120 mcg on two thin dissolvable films for sublingual administration; Other Names: IGALMI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Alejandra Gonzalez-Duarte, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 7, 2023
• First Submitted That Met QC Criteria: November 7, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Hereditary Sensory and Autonomic Neuropathies; Primary Dysautonomias; Autonomic Nervous System Diseases; Dysautonomia, Familial; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 23-00174

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Alejandra.gonzalez-duarte@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
• IPD Sharing 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.
• IPD Sharing 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No