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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called dexmedetomidine (also known as Precedex) to help individuals with Familial Dysautonomia (FD) manage sudden autonomic crises. The researchers aim to determine if this treatment can effectively calm these crises and if monitoring heart rate, blood pressure, and oxygen levels can predict when a crisis will occur. Participants will receive either the actual treatment or a placebo to compare results. This trial is suitable for those with a confirmed FD diagnosis who have experienced at least one autonomic crisis in the past year. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that dexmedetomidine is likely to be safe for humans?

Research has shown that dexmedetomidine is generally safe for people with Familial Dysautonomia (FD). In past studies, patients with FD received dexmedetomidine through an IV to help manage severe stress episodes, and these studies found it to be safe and possibly helpful in calming these episodes.

Dexmedetomidine is also approved for use in other conditions in some countries, indicating it has passed safety tests in humans. However, no specific studies are planned to focus on its use for sudden nervous system disruptions in people with FD.

Overall, while existing research and approvals suggest the treatment is safe, more studies are needed to confirm its safety specifically for these nervous system disruptions in FD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Familial Dysautonomia?

Dexmedetomidine is unique for treating Familial Dysautonomia because it is delivered via a sublingual film, allowing for quick absorption directly into the bloodstream. This method is less invasive compared to other treatments that might require injections or more complex administration. Additionally, dexmedetomidine acts as a selective alpha-2 adrenergic agonist, which can help manage autonomic crises by calming the nervous system more effectively and potentially with fewer side effects. Researchers are excited about this treatment because it offers a novel approach that could provide rapid relief during acute episodes, improving patient comfort and convenience.

What evidence suggests that dexmedetomidine might be an effective treatment for Familial Dysautonomia?

Research has shown that dexmedetomidine can help reduce symptoms during sudden health episodes in people with Familial Dysautonomia (FD). In this trial, participants will receive sublingual dexmedetomidine, which previous studies have demonstrated can significantly lower high blood pressure, with the top number dropping from 160 to 122 within an hour. Another study found that using dexmedetomidine as a nasal spray eased symptoms during these episodes. Additionally, hospital experiences indicated that dexmedetomidine often reduced both blood pressure and heart rate. Overall, these findings suggest that dexmedetomidine holds promise for managing these episodes in FD. ^{4 5 6 7 8}

Who Is on the Research Team?

Alejandra Gonzalez-Duarte, MD

Principal Investigator

NYU Langone Health, NYU Dysautonomia Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27752785/

Dexmedetomidine for refractory adrenergic crisis in familial ... At 1 h after the initiation of dexmedetomidine, systolic BP decreased from 160 ± 7 to 122 ± 7 mmHg (p = 0.0005), diastolic BP decreased from 103 ± 6 to 65 ± 8 ( ...

2. withpower.com withpower.com/trial/phase-2-primary-dysautonomias-11-2023-e3d8c

Dexmedetomidine for Familial Dysautonomia Intranasal dexmedetomidine, administered at a dose of 2 mcg/kg, effectively alleviated symptoms of adrenergic crisis in three patients with familial ...

3. cureus.com cureus.com/articles/115863-experience-with-dexmedetomidine-use-in-the-treatment-of-dysautonomic-crisis-in-familial-dysautonomia-an-off-label-use

Experience With Dexmedetomidine Use in the Treatment ... The nine patients had 14 hospital admissions, and in 10 out of the 14 admissions, there was a decrease in blood pressure and heart rate after ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5555081/

Intranasal dexmedetomidine for adrenergic crisis in familial ... In conclusion, this case series shows that intranasal dexmedetomidine is a feasible and apparently safe treatment for adrenergic crisis in patients with FD.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0007091217339806

Perioperative use of dexmedetomidine in an infant with ... The use of dexmedetomidine in the treatment of dysautonomia crisis associated with FD is not known. However, its use during such crisis, a condition known to be ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5292083/

Dexmedetomidine for Refractory Adrenergic Crisis in Familial ... Intravenous dexmedetomidine is safe in patients with FD and appears to be effective to treat refractory adrenergic crisis.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06148311

NCT06148311 | Dexmedetomidine Sublingual Film for the ... Our database shows evidence of autonomic crisis, previous treatment with IV dexmedetomidine, and registered medical data within the year preceding the study.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9636886/

Experience With Dexmedetomidine Use in the Treatment of ... There are no prospective studies evaluating the use of dexmedetomidine in dysautonomic crises. Further, familial dysautonomia is a rare disease, ...