Clinical trial NCT06943404: BXCL501 After Stress to Increase Recovery Success
Official title: Prevention/Reduction of ASRs and PTSD to Sustain Civilian Performance With a Sublingual Formulation of Dexmedetomidine (BXCL501)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Acute Stress Reaction
Acute Stress Disorder
Post-traumatic Stress Disorder
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Mclean Hospital
name: Washington University School of Medicine
name: University of Florida
name: Rhode Island Hospital
name: Vanderbilt University School of Medicine
name: Walter Reed Army Institute of Research (WRAIR)
First posted: 2025-04-24
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will examine the safety and efficacy of BXCL501 to reduce ASR symptoms and behavioral changes among patients presenting to the Emergency Department (ED) after Motor Vehicle Collision (MVC). Specifically, the investigators will perform the BXCL501 (BASIS) Trial, a double-blind placebo-controlled Randomized Controlled Trial (RCT) to determine if BXCL501 (dexmedetomidine hydrochloride sublingual film) initiated in the ED in the hours after MVC to high risk individuals, treats/reduces ASR/ASD symptoms (primary outcome), improves neurocognitive function, and prevents/reduces posttraumatic stress (PTS) symptoms (secondary outcomes) long term. 100 participants will be randomized, receive study drug in ED and be discharged with a 2-week drug supply. Prior to initial dose of study drug administration, and during the hours, days, and weeks after participants will receive serial longitudinal assessments of psychological and somatic symptoms, neurocognitive function, and adverse events.

Detailed description: U.S. military personnel are exposed to life-threatening traumatic events (e.g., intense firefights with multiple casualties) that result in acute stress reaction (ASR) symptoms (ICD-10) and posttraumatic stress (PTS). Similarly, acute and persistent stress symptoms, and related adverse posttraumatic neuropsychiatric sequelae, are also very common and cause a tremendous burden of suffering in civilian populations following exposure to life-threatening traumatic events (e.g., motor vehicle collision, violent or accidental death of a loved one, and assault). BXCL501 (dexmedetomidine HCl sublingual film) has been evaluated in multiple clinical trials across a range of medical conditions (dementia, schizophrenia, bipolar disorder, opioid use disorder), with an excellent safety profile, and evidence of efficacy with respect to decreasing agitation. This is promising for the treatment of ASRs, as agitation is a primary feature of ASRs in many individuals. Additionally, adrenergic hyperactivity is also a key characteristic of ASRs and contributes to the development of Posttraumatic Stress Disorder (PTSD). BXCL501 is known to decrease the activity of central noradrenergic neurons, suggesting a mechanistic pathway by which BXCL501 may improve outcomes for individuals at risk of ASR/ASD/PTSD. BXCL501 therefore holds significant promise as a treatment aimed at reducing ASR symptoms and related behavioral changes, enhancing resilience and improving warfighter performance, and reducing the frequency and severity of persistent/chronic PTS symptoms. This study will evaluate the safety and efficacy of BXCL501 in a population of trauma survivors at high risk for developing ASR, ASD, and PTSD symptoms, and may ultimately provide military personnel, veterans, and civilians with an important new treatment option to improve recovery, job performance, and quality of life when administered in the early aftermath of exposure to a traumatic stressor.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 years and ≤ 65 years of age
* Admitted to ED within 24 hours of MVC
* Anticipated to be discharged home from the ED
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Consent to receive unencrypted communications
* Has a smartphone with continuous service for ≥ 1 year
* Has a personal email address they regularly access
* Able to speak and read English
* PTS prediction tool risk score ≥ 16 in the ED
* Females of childbearing potential (not surgically sterilized (tubal ligation/hysterectomy) or not post-menopausal (no menstrual period for \> 6 months)) must be willing to use a medically acceptable and effective birth control method for 3 months before the study and while participating in the study. Medically acceptable methods of contraception that may be used by the participant include abstinence, birth control pills or patches, birth control implants, diaphragm, intrauterine device (IUD), or condoms.

Exclusion Criteria:

* Substantial comorbid injury (e.g., long bone fracture)
* People of childbearing potential who are pregnant, breastfeeding, planning to become pregnant, or not using a highly effective form of contraception (e.g., implants, intrauterine devices (IUDs), tubal ligation, hormonal birth control pills, patches, vaginal rings, or injections) during their participation
* Prisoner status
* Chronic daily opioid use prior to MVC (\> 20 mg oral daily morphine equivalents)
* Bipolar disorder, psychotic disorder, active psychosis, suicidal ideation, or homicidal ideation
* Plans for hospital admission
* Clinically significant history of cardiac disease including (a) history of syncope or other syncopal attacks; (b) current evidence of orthostatic hypotension (defined as a decrease in systolic BP of 20 mm Hg or decrease in diastolic BP of 10 mm Hg within 3 minutes); (c) resting heart rate of \<55 beats per minute; (d) systolic blood pressure \<110 mm Hg or diastolic BP \<70 mm Hg; (e) participants with a corrected QT interval (QTc) interval \>440msec (males) or \>460msec (females) not in sinus rhythm; or 1st, 2nd or 3rd degree hearth block; or (f) history of severely impaired ventricular function (ejection fraction \< 30%).
* Hypomagnesia (\<1.7 mg/dL) or hypokalemia (\< 3.0 Milliequivalents (mEq/L))
* Substantial hepatic impairment (e.g. Aspartate Transaminase (AST) or Alanine Transaminase (ALT) \> 3 times the upper limit of normal or history of cirrhosis).
* Currently taking the following medications: a) medications for alcoholism (e.g. naltrexone, disulfiram, topiramate, acamprosate); b) psychotropic medications that promote sedation including sedative/hypnotics, barbiturates, antihistamines, sedative antidepressants (e.g. doxepin, mirtazapine, trazodone), and triptans (e.g., sumatriptan); c) alpha-2-adrenergic agonists (clonidine, guanfacine, lofexidine); d) or adrenergic agents prescribed for other reasons (prazosin). (Permitted Concomitant Medications: The concomitant medications allowed in the study include non-sedative antidepressants used to treat PTSD)
* Hypersensitivity or history of allergic reaction to dexmedetomidine
* Lacking capacity to provide informed consent (receipt of sedative, hypnotic agent making the patient non-decisional for consent)

Primary outcomes:
measure: Change in ASD Score
timeFrame: Week 1, 3 after MVC
Secondary outcomes:
measure: Median reaction time of correct responses (general cognitive function)
timeFrame: Min 30, Hour 1, 6, 12, Day 1, 2, 3, Week 1, 2, 3, 5, 6, 8, 11, 12 after MVC
measure: Median reaction time of correct responses (procedural reaction time)
timeFrame: Min 30, Hour 1, 6, 12, Day 1, 2, 3, Week 1, 2, 3, 5, 6, 8, 11, 12 after MVC
measure: Proportion of targets correctly identified (visuospatial processing and attention)
timeFrame: Min 30, Hour 1, 6, 12, Day 1, 2, 3, Week 1, 2, 3, 5, 6, 8, 11, 12 after MVC
measure: d-prime identification (psychomotor vigilance)
timeFrame: Min 30, Hour 1, 6, 12, Day 1, 2, 3, Week 1, 2, 3, 5, 6, 8, 11, 12 after MVC
measure: Change in Pain Symptom Score
timeFrame: Baseline, Week 1, 3, 6, 12 after MVC
measure: Change in Depressive Symptoms Score
timeFrame: Baseline, Week 1, 3, 6, 12 after MVC
measure: Change in Somatic Symptom Score
timeFrame: Baseline, Week 1, 3, 6, 12 after MVC
measure: Change in PTSD Symptoms
timeFrame: Baseline, Week 1, 3, 6, 12 after MVC
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: University of Florida College of Medicine - Jacksonville
state: Florida
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
Study officials:
affiliation: University of North Carollina at Chapel Hill
name: Samuel McLean, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Stacey House, MD
role: PRINCIPAL_INVESTIGATOR
References: