Dexmedetomidine for Familial Dysautonomia

Overseen By Alejandra Gonzalez-Duarte, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Must be taking: Dexmedetomidine

Disqualifiers: Pregnancy, Cognitive impairment, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 hours per episode

15 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug dexmedetomidine for treating familial dysautonomia?

Dexmedetomidine has been shown to effectively treat adrenergic crises in familial dysautonomia, especially when other treatments like clonidine and benzodiazepines were ineffective. It helps manage symptoms like high blood pressure and rapid heart rate without causing excessive sedation. ^{1 2 3 4 5}

Is dexmedetomidine safe for use in humans?

Dexmedetomidine is generally well-tolerated in humans, often used for sedation without causing respiratory depression (breathing problems). However, it can cause low blood pressure (hypotension) and slow heart rate (bradycardia), which usually resolve on their own. There is a rare risk of serious heart issues, as seen in a case of cardiac arrest during a procedure. ^{1 3 6 7 8}

How is the drug dexmedetomidine unique for treating familial dysautonomia?

Dexmedetomidine is unique for treating familial dysautonomia because it is a selective α2-adrenergic agonist that acts centrally, offering greater selectivity and a shorter half-life than clonidine, which is traditionally used. It can be administered intranasally or intravenously and is effective in resolving symptoms of adrenergic crises without causing excessive sedation or respiratory depression, unlike other treatments such as benzodiazepines. ^{1 2 3 5 9}

Research Team

Alejandra Gonzalez-Duarte, MD

Principal Investigator

NYU Langone Health, NYU Dysautonomia Center

Eligibility Criteria

This trial is for individuals aged 16 or older with a genetic diagnosis of Familial Dysautonomia who've had an autonomic crisis in the past year. They must be willing to follow study procedures, use condoms if sexually active, have a responsible caretaker, and provide informed consent. Excluded are those with low oxygen levels, high respiratory rates, very low blood pressure, fever/infection signs recently or pregnant women.

Inclusion Criteria

I have a genetic diagnosis of Familial Dysautonomia.

I am 16 years old or older.

I use condoms for birth control if I am sexually active.

Exclusion Criteria

The Montreal Cognitive Exam (MoCA) is below 25 points

My oxygen levels are below 92% without extra oxygen or I need more oxygen than before.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dexmedetomidine or placebo sublingual film during autonomic crisis, with monitoring of vital signs and symptoms

Up to 2 hours per episode

As needed during autonomic crisis

Follow-up

Participants are monitored for safety and effectiveness after treatment, including reduction in hospital stay and medical complications

Up to 48 months

Treatment Details

Interventions

• Dexmedetomidine

Trial Overview The study tests dexmedetomidine as a sublingual film against a placebo to manage hyperadrenergic autonomic crises in patients with Familial Dysautonomia. It aims to see if it's feasible and whether heart rate, blood pressure and oxygen saturation can predict the onset of these crises.

Participant Groups

Group I: Sublingual dexmedetomidine Experimental Treatment 1 Intervention

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.

Group II: Matching Sublingual Placebo Placebo Group 1 Intervention

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.

Dexmedetomidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in United States as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in Canada as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in Japan as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

Intranasal dexmedetomidine, administered at a dose of 2 mcg/kg, effectively alleviated symptoms of adrenergic crisis in three patients with familial dysautonomia within 8-17 minutes, normalizing their blood pressure and heart rate.

This case series suggests that intranasal dexmedetomidine is a safe and feasible option for acute treatment of adrenergic crises, but further controlled studies are needed to confirm its efficacy and safety in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia. Spalink, CL., Barnes, E., Palma, JA., et al.[2018]

In a study of 9 patients with familial dysautonomia (FD), intravenous dexmedetomidine effectively reduced blood pressure and heart rate during refractory adrenergic crises, showing significant improvements within 1 hour of administration.

Dexmedetomidine was found to be safe, with a low incidence of adverse events, suggesting it could be a beneficial alternative for patients who do not respond to traditional treatments like clonidine and benzodiazepines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine for refractory adrenergic crisis in familial dysautonomia. Dillon, RC., Palma, JA., Spalink, CL., et al.[2018]

Intravenous dexmedetomidine is effective for sedation in mechanically ventilated patients and during procedures, reducing the need for additional sedatives like propofol or midazolam.

It is generally well tolerated, does not cause respiratory depression, and while it may lead to hypotension and bradycardia, these side effects typically resolve on their own.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine: a guide to its use for sedation in the US. Keating, GM., Hoy, SM., Lyseng-Williamson, KA.[2022]

Treatment for familial dysautonomia has significantly improved the health and survival rates of patients, addressing not only the neurological aspects but also secondary systemic issues affecting various bodily functions.

Preventative and supportive therapies, including medications for symptom management and surgical interventions, are crucial in managing the disorder, and advances in genetic understanding may lead to future gene-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Familial dysautonomia: a review of the current pharmacological treatments. Axelrod, FB.[2019]

A 19-year-old male with familial dysautonomia experienced a severe dysautonomic crisis that was resistant to conventional treatments like oral labetalol and clonidine, highlighting the challenges in managing this condition.

Intravenous dexmedetomidine was successfully used to resolve the patient's symptoms within hours, suggesting it may be a safe and effective alternative treatment for dysautonomic crises when standard therapies fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience With Dexmedetomidine Use in the Treatment of Dysautonomic Crisis in Familial Dysautonomia: An Off-Label Use. Subedi, A., Sharma, R., Lalani, I.[2022]

In a study involving 91 pediatric patients, dexmedetomidine was found to be a well-tolerated alternative sedative for non-intubated moderate or deep sedation, with a low incidence of serious adverse events.

While respiratory depression and hypotension were the most common treatment-emergent adverse events, they were manageable and consistent with dexmedetomidine's known safety profile, indicating its potential for safe use in children during elective procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation. Jooste, EH., Hammer, GB., Reyes, CR., et al.[2020]

Dexmedetomidine is commonly used as a safe sedative during surgeries, but there are rare cases where it can lead to serious complications, such as cardiac arrest.

In this report, a 76-year-old woman experienced cardiac arrest during a pacemaker lead extraction procedure while being treated with dexmedetomidine, highlighting the need for careful monitoring in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. Shah, AN., Koneru, J., Nicoara, A., et al.[2013]

Patients with familial dysautonomia (FD) experience significantly higher rates of adverse drug reactions compared to the general population, with 31 out of 123 drugs showing increased side effects such as gastrointestinal bleeding and bronchospasm.

The study identified eight genes that are differentially expressed in FD patients, which may explain their heightened sensitivity to certain medications, suggesting that some common drugs should be avoided or used with caution in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uncommon side effects of common drugs in patients with familial dysautonomia. Perl, L., Hakimian, D., Maayan, C., et al.[2022]

Dexmedetomidine is an effective sedative for mechanically ventilated patients and during surgical procedures, requiring less rescue sedation compared to placebo, which indicates its efficacy in maintaining optimal sedation levels.

It is generally well tolerated, with a lower incidence of postoperative delirium and no respiratory depression, although it can cause hypotension and bradycardia, which typically resolve without treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine: a review of its use for sedation in mechanically ventilated patients in an intensive care setting and for procedural sedation. Hoy, SM., Keating, GM.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Dexmedetomidine for refractory adrenergic crisis in familial dysautonomia. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Dexmedetomidine: a guide to its use for sedation in the US. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Familial dysautonomia: a review of the current pharmacological treatments. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Experience With Dexmedetomidine Use in the Treatment of Dysautonomic Crisis in Familial Dysautonomia: An Off-Label Use. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Uncommon side effects of common drugs in patients with familial dysautonomia. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Dexmedetomidine: a review of its use for sedation in mechanically ventilated patients in an intensive care setting and for procedural sedation. [2022]