Dexmedetomidine for Familial Dysautonomia
Recruiting in Palo Alto (17 mi)
Overseen byAlejandra Gonzalez-Duarte, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: NYU Langone Health
Disqualifiers: Low oxygen, High respiratory rate, Low blood pressure, Fever, Infection, others
No Placebo Group
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
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 heartbeat without causing excessive sedation.
12345Is dexmedetomidine safe for use in humans?
Dexmedetomidine is generally well-tolerated in humans, often used for sedation without causing respiratory depression. 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.
15678How 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 can be administered intranasally or intravenously, offering a more targeted and shorter-acting alternative to traditional treatments like clonidine and benzodiazepines, which can cause excessive sedation and respiratory issues.
145910Eligibility Criteria
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
+5 more
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
+1 more
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Sublingual dexmedetomidineExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
NYU Langone HealthNew York, NY
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Who Is Running the Clinical Trial?
NYU Langone HealthLead Sponsor
References
Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia. [2018]Label="PURPOSE" NlmCategory="OBJECTIVE">To report the use of intranasal dexmedetomidine, an α2-adrenergic agonist for the acute treatment of refractory adrenergic crisis in patients with familial dysautonomia.
Experience With Dexmedetomidine Use in the Treatment of Dysautonomic Crisis in Familial Dysautonomia: An Off-Label Use. [2022]Familial dysautonomia is a rare genetic neurodevelopmental disorder characterized by episodes of hyperautonomic state known as dysautonomic crises. The features of dysautonomic crises are hypertension, tachycardia, vomiting, sweating, flushing, and behavioral changes. The etiology of such crises is supposed to be a consequence of the inability to control sympathetic overflow due to damage to the afferent neurons carrying baroreceptor inputs to the central nervous system. A 19-year-old male with a known history of familial dysautonomia and frequent dysautonomic crises presented to the Emergency Department with intractable nausea and vomiting for six hours. He was hypertensive and tachycardic on presentation. The patient had tried oral labetalol and clonidine at home with no improvement. In the emergency room, the patient received intravenous labetalol, diazepam, and clonidine which were ineffective. He was then treated with intravenous dexmedetomidine, and his symptoms resolved within a few hours. The patient was discharged home on the same day. The mainstay of treatment for dysautonomic crises is benzodiazepines and clonidine. The use of these treatment modalities has its challenges. Here, we present a case of a dysautonomic crisis that was resistant to the conventional treatment, treated safely and successfully with dexmedetomidine.
Familial dysautonomia: a review of the current pharmacological treatments. [2019]Treatment of familial dysautonomia, a genetic disorder affecting neuronal development and survival, has improved morbidity and survival for this disorder. Although this is primarily a neurological disorder causing sensory and autonomic dysfunction, there are secondary systemic perturbations affecting ophthalmological, gastrointestinal, respiratory, cardiovascular, orthopaedic and renal function. Penetrance is complete, but there is marked variability in expression. Preventative and supportive treatments have included measures to maintain eye moisture, fundoplication with gastrostomy, the use of central agents such as benzodiazepines and clonidine to control vomiting and the dysautonomic crisis, and fludrocortisone and midodrine to combat cardiovascular lability. With the identification of the familial dysautonomia gene, it has been suggested that it may be possible to treat patients by modifying production and expression of the genetic product.
Dexmedetomidine for refractory adrenergic crisis in familial dysautonomia. [2018]Label="OBJECTIVE">Adrenergic crises are a cardinal feature of familial dysautonomia (FD). Traditionally, adrenergic crises have been treated with the sympatholytic agent clonidine or with benzodiazepines, which can cause excessive sedation and respiratory depression. Dexmedetomidine is a centrally-acting α 2-adrenergic agonist with greater selectivity and shorter half-life than clonidine. We evaluated the preliminary effectiveness and safety of intravenous dexmedetomidine in the treatment of refractory adrenergic crisis in patients with FD.
Dexmedetomidine: a guide to its use for sedation in the US. [2022]Intravenous dexmedetomidine (Precedex(®)) provides both effective sedation in mechanically ventilated patients in an intensive care setting and effective procedural sedation. In these patient populations, it reduces the need for rescue sedation with intravenous propofol or intravenous midazolam and reduces opioid requirements. In addition, patients receiving dexmedetomidine are calm and easy to arouse and manage. Intravenous dexmedetomidine is generally well tolerated and is not associated with respiratory depression. Although the utilization of dexmedetomidine is associated with hypotension and bradycardia, both usually resolve without intervention.
Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation. [2020]Dexmedetomidine (Precedex™) may be used as an alternative sedative in children, maintaining spontaneous breathing, and avoiding tracheal intubation in a non-intubated moderate or deep sedation (NI-MDS) approach. This open-label, single-arm, multicenter study evaluated the safety of dexmedetomidine in a pediatric population receiving NI-MDS in an operating room or a procedure room, with an intensivist or anesthesiologist in attendance, for elective diagnostic or therapeutic procedures expected to take at least 30 min. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Patients received one of two doses dependent on age: patients aged ≥28 weeks' gestational age to <1 month postnatal received dose level 1 (0.1 μg/kg load; 0.05-0.2 μg/kg/h infusion); those aged 1 month to <17 years received dose level 2 (1 μg/kg load; 0.2-2.0 μg/kg/h infusion). Sedation efficacy was assessed and defined as adequate sedation for at least 80% of the time and successful completion of the procedure without the need for rescue medication. In all, 91 patients were enrolled (dose level 1, n = 1; dose level 2, n = 90); of these, 90 received treatment and 82 completed the study. Eight patients in dose level 2 discontinued treatment for the following reasons: early completion of diagnostic or therapeutic procedure (n = 3); change in medical condition (need for intubation) requiring deeper level of sedation (n = 2); adverse event (AE; hives and emesis), lack of efficacy, and physician decision (patient not sedated enough to complete procedure; n = 1 each). Sixty-seven patients experienced 147 TEAEs. The two most commonly reported AEs were respiratory depression (bradypnea; reported per protocol-defined criteria, based on absolute respiratory rate values for age or relative decrease of 30% from baseline) and hypotension. Four patients received glycopyrrolate for bradycardia and seven patients received intravenous fluids for hypotension. SpO2 dropped by 10% in two patients, but resolved without need for manual ventilation. All other reported AEs were consistent with the known safety profile of dexmedetomidine. Two of the 78 patients in the efficacy-evaluable population met all sedation efficacy criteria. Dexmedetomidine was well-tolerated in pediatric patients undergoing procedure-type sedation.
Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. [2013]Dexmedetomidine (Precedex), an alpha-2 adrenergic receptor agonist is frequently and safely used as sedative agent during surgical procedures. We report a case of a 76-year-old woman who developed cardiac arrest from the use of dexmedetomidine during pacemaker lead extraction procedure.
Uncommon side effects of common drugs in patients with familial dysautonomia. [2022]Patients with the autosomal recessive disorder of familial dysautonomia typically exhibit exacerbated adverse side effects to many common drugs. We aimed to catalog these adverse effects - with a focus on common drugs that are frequently administered to FD patients and compare their incidences to those within the general population.
Dexmedetomidine: a review of its use for sedation in mechanically ventilated patients in an intensive care setting and for procedural sedation. [2022]Dexmedetomidine (Precedex®), a pharmacologically active dextroisomer of medetomidine, is a selective α(2)-adrenergic receptor agonist. It is indicated in the US for the sedation of mechanically ventilated adult patients in an intensive care setting and in non-intubated adult patients prior to and/or during surgical and other procedures. This article reviews the pharmacological properties, therapeutic efficacy and tolerability of dexmedetomidine in randomized, double-blind, placebo-controlled, multicentre studies in these indications. Post-surgical patients in an intensive care setting receiving dexmedetomidine required less rescue sedation with intravenous propofol or intravenous midazolam to achieve and/or maintain optimal sedation during the assisted ventilation period than placebo recipients, according to two randomized, double-blind, multinational studies. Moreover, significantly more dexmedetomidine than placebo recipients acquired and/or maintained optimal sedation without rescue sedation. Sedation with dexmedetomidine was also effective in terms of the total dose of morphine administered, with dexmedetomidine recipients requiring less morphine than placebo recipients; with regard to patient management, dexmedetomidine recipients were calmer and easier to arouse and manage than placebo recipients. Intravenous dexmedetomidine was effective as a primary sedative in two randomized, double-blind, placebo-controlled, multicentre studies in adult patients undergoing awake fibre-optic intubation or a variety of diagnostic or surgical procedures requiring monitored anaesthesia care. In one study, significantly fewer dexmedetomidine than placebo recipients required rescue sedation with intravenous midazolam to achieve and/or maintain optimal sedation; conversely, in another study, rescue sedation with intravenous midazolam was not required by significantly more dexmedetomidine than placebo recipients. Primary sedation with intravenous dexmedetomidine was also effective in terms of the secondary efficacy endpoints, including the mean total dose of midazolam and fentanyl administered and the percentage of patients requiring further sedation (in addition to dexmedetomidine or placebo and midazolam), with, for the most part, significant between-group differences observed in favour of dexmedetomidine over placebo. In general, no significant differences were observed between the dexmedetomidine and placebo treatment groups in the anaesthesiologists' assessment of ease of intubation, haemodynamic stability, patient cooperation and/or respiratory stability. Intravenous dexmedetomidine is generally well tolerated when utilized in mechanically ventilated patients in an intensive care setting and for procedural sedation in non-intubated patients. Dexmedetomidine is associated with a lower rate of postoperative delirium than midazolam or propofol; it is not associated with respiratory depression. While dexmedetomidine is associated with hypotension and bradycardia, both usually resolve without intervention. Thus, intravenous dexmedetomidine provides a further option as a short-term (
[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis]. [2015]Dexmedetomidine (Precedex®)is an agonist of a2-adrenergic receptors in certain parts of the brain. It was approved for "procedural sedation in the non-intubation in under local anesthesia" in June 2013 in Japan. However, because of metabolism delay, dexmedetomidine has to be administered carefully to patients with liver dysfunction.