BXCL501 given shortly after a car crash to reduce acute stress and later PTSD symptoms

Prevention/Reduction of ASRs and PTSD to Sustain Civilian Performance With a Sublingual Formulation of Dexmedetomidine (BXCL501)

This will test whether a short course of BXCL501 sublingual film given in the emergency department after a motor vehicle collision can reduce acute stress symptoms and lower the chance of developing PTSD in high‑risk adults.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University of North Carolina, Chapel Hill (Academic / other)
• Locations: 3 sites (Jacksonville, Florida and 2 other locations)
• Trial ID: NCT06943404 on ClinicalTrials.gov

What this trial studies

This is a randomized, double‑blind, placebo‑controlled Phase 2 trial enrolling about 100 adults who present to the ED within 72 hours of a motor vehicle collision and are expected to be discharged home. Participants receive a first dose in the ED and are discharged with a two‑week supply of BXCL501 (dexmedetomidine HCl sublingual film) or placebo, with serial assessments in the hours, days, and weeks afterward. The primary outcome is reduction in acute stress reaction/acute stress disorder symptoms, with secondary outcomes including neurocognitive function and longer‑term posttraumatic stress symptoms, plus monitoring of safety and adverse events. The design leverages prior safety data for BXCL501 in other disorders but applies the drug acutely after trauma to try to alter early stress responses.

Who should consider this trial

Good fit: Adults 18–65 who come to the ED within 72 hours of a motor vehicle collision, are expected to be discharged home, can read and speak English, have a smartphone and email for follow‑up, and (if of childbearing potential) agree to effective contraception are the intended participants.

Not a fit: People who are hospitalized for severe injuries, have major medical or psychiatric contraindications to dexmedetomidine, cannot use a smartphone or comply with follow‑up, or fall outside the 18–65 age range are unlikely to benefit from this study intervention.

Why it matters

Potential benefit: If successful, the treatment could quickly reduce acute stress symptoms after trauma and lower the risk of persistent PTSD, improving short‑term recovery and longer‑term functioning.

How similar studies have performed: BXCL501 has demonstrated safety and reduced agitation in other clinical trials for disorders like dementia and schizophrenia, but using it acutely after trauma to prevent PTSD is a novel application with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. ≥ 18 years and ≤ 65 years of age
2. Admitted to ED within 72 hours of MVC
3. Anticipated to be discharged home from the ED
4. Stated willingness to comply with all study procedures and availability for the duration of the study
5. Consent to receive unencrypted communications
6. Has a smartphone with continuous service for ≥ 1 year
7. Has a personal email address they regularly access
8. Able to speak and read English
9. Females of childbearing potential (not surgically sterilized (tubal ligation/hysterectomy) or not post-menopausal (no menstrual period for \> 12 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:

1. Substantial comorbid injury (e.g., long bone fracture)
2. 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
3. Prisoner status
4. Chronic daily opioid use prior to MVC (\> 20 mg oral daily morphine equivalents)
5. Bipolar disorder, psychotic disorder, active psychosis, suicidal ideation, or homicidal ideation
6. Hospital admission
7. 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 10mm Hg within 3 minutes); (c) resting heart rate of \<55 beats per minute; (d) systolic blood pressure \<110mmHg or diastolic BP \<70mmHg; (e) participants with a 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%).
8. Hypomagnesia (\<1.7 mg/dL) or hypokalemia (\< 3.0 mEq/L)
9. Substantial hepatic impairment (e.g. AST or ALT \> 3 times the upper limit of normal or history of cirrhosis).
10. 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) adrenergic agents prescribed for other reasons (prazosin); e) or medications known to cause QT prolongation. (Permitted Concomitant Medications: The concomitant medications allowed in the study include non-sedative antidepressants used to treat PTSD)
11. Hypersensitivity or history of allergic reaction to dexmedetomidine
12. Lacking capacity to provide informed consent (receipt of sedative, hypnotic agent making the patient non-decisional for consent)
13. Any other history or condition that would, in the site investigator's judgement, indicate that the patient would very likely be non-compliant with the study or unsuitable for the study (e.g., might interfere with the study, confound interpretation, or endanger patient)
14. Participation in any other clinical trial of a pharmacological agent within 30 days prior to screening.

Where this trial is running

Jacksonville, Florida and 2 other locations

• University of Florida College of Medicine - Jacksonville — Jacksonville, Florida, United States (Recruiting)
• Washington University in St. Louis — St Louis, Missouri, United States (Not_yet_recruiting)
• UVA University Hospital — Charlottesville, Virginia, United States (Recruiting)

Study contacts

• Principal investigator: Samuel McLean, MD — University of North Carollina at Chapel Hill
• Study coordinator: Romina Soudavari, MPH

Conditions Acute Stress Reaction; Acute Stress Disorder; Post-traumatic Stress Disorder