Dexmedetomidine for Familial Dysautonomia

Overseen By Horacio Kaufmann, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NYU Langone Health

Disqualifiers: Low oxygen, High respiratory rate, Low blood pressure, Fever, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether dexmedetomidine (also known as Precedex), administered as a film under the tongue, can help manage severe autonomic crises at home for individuals with Familial Dysautonomia. The trial focuses on the treatment's effectiveness in controlling these crises and improving their monitoring and assessment. Individuals diagnosed with Familial Dysautonomia who have experienced at least one autonomic crisis in the past year may qualify for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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, when used as a sublingual film (a small strip placed under the tongue), might be safe for patients with Familial Dysautonomia to use at home during certain medical emergencies. Previous studies tested a similar approach using dexmedetomidine in a nasal spray and found it safe for these emergencies.

Dexmedetomidine is already approved for use in some medical situations, indicating its safety is well-documented. Although this study is in the early stages, the drug's use in other settings suggests it could be safe.

Generally, drugs at this stage of research have shown initial safety in humans but require more testing for confirmation. Participants should discuss any concerns with the trial team to understand what these findings mean for them. ^{1 2 3 4 5}

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

Dexmedetomidine is unique because it's delivered sublingually as a film, which is different from the typical administration methods for familial dysautonomia treatments, such as oral or intravenous medications. This method can provide rapid relief during autonomic crises by allowing the medication to be absorbed quickly through the tissue under the tongue. Additionally, dexmedetomidine offers a novel approach by targeting specific receptors in the nervous system, potentially providing a more focused and effective response compared to current treatment options that may have broader effects. Researchers are excited about this treatment because it could lead to faster and more efficient management of symptoms, improving the quality of life for patients with familial dysautonomia.

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

Research shows that dexmedetomidine can help treat symptoms of adrenergic crises in people with familial dysautonomia. Earlier studies demonstrated that administering dexmedetomidine nasally at a dose of 2 mcg/kg eased symptoms in three patients during these crises. In this trial, participants will receive dexmedetomidine as a film that dissolves under the tongue. The positive results from the nasal form suggest that the sublingual form might also be effective. This treatment calms the nervous system, potentially stopping the crises. Early evidence supports its potential effectiveness and safety for managing these challenging episodes. ^{2 3 4 5 6}

Who Is on the Research Team?

Alejandra Gonzalez-Duarte, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a genetic diagnosis of Familial Dysautonomia who've had at least one autonomic crisis in the past year and tolerated IV dexmedetomidine. They must have a caregiver, give informed consent, and use contraception if needed. Exclusions include certain health conditions during crises or inability to understand the protocol.

Inclusion Criteria

One or more autonomic crises during the last year

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

Exclusion Criteria

My caregiver might not fully understand the study or communicate well in emergencies.

I am a woman and my pregnancy test is positive.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sublingual dexmedetomidine film at home to treat hyperadrenergic autonomic crises

6 months

Home-based administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexmedetomidine

Trial Overview The study tests if sublingual dexmedetomidine film can be used at home to stop hyperadrenergic autonomic crises in Familial Dysautonomia patients. It's an open-label pilot study aiming to see if such trials are feasible and how well the treatment works outside of a hospital setting.

How Is the Trial Designed?

Group I: Sublingual dexmedetomidine Experimental Treatment 1 Intervention

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.

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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 of 30 patients with liver dysfunction undergoing percutaneous arterial chemoembolization for hepatocellular carcinoma, dexmedetomidine sedation was successfully used in all cases, demonstrating its feasibility for this procedure.

The sedation was generally safe, with only minor adverse events reported in 3 patients, and no serious complications requiring treatment, indicating that dexmedetomidine can be a reliable option for sedation in patients with liver issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis]. Komemushi, A., Suzuki, S., Sano, A., et al.[2015]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06148311?cond=HSAN&viewType=Table&rank=3

NCT06148311 | Dexmedetomidine Sublingual Film for the ... A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.

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. app.trialscreen.org app.trialscreen.org/trials/phase-2-dexmedetomidine-sublingual-film-ambulatory-treatment-hyperadrenergic-trial-nct06148311

Dexmedetomidine Sublingual Film for the Ambulatory ... A Phase 2 interventional study of dexmedetomidine in Familial Dysautonomia. Evaluating the effectiveness of dexmedetomidine sublingual film in treating ...

4. trial.medpath.com trial.medpath.com/clinical-trial/53157fbd5ca236fa/nct06148311-dexmedetomidine-sublingual-film-hyperadrenergic-autonomic-crisis

Dexmedetomidine Sublingual Film for the Ambulatory ... The purpose of this placebo controlled interventional study is to collect preliminary data on administering dexmedetomidine in patients with Familial ...

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

Intranasal dexmedetomidine for adrenergic crisis in familial ... Intranasal dexmedetomidine is a feasible and safe acute treatment for adrenergic crisis in patients with familial dysautonomia.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06148311

NCT06148311 | Dexmedetomidine Sublingual Film for the ... The purpose of this placebo controlled interventional study is to collect preliminary data on administering dexmedetomidine in patients with Familial ...