Using TNX-102 SL to reduce acute stress reactions after motor vehicle collisions

Prevention/Reduction of ASRs and PTSD to Sustain Civilian Performance With Sublingual Cyclobenzaprine HCl (TNX-102 SL) - (Optimizing Acute Stress Reaction Interventions With TNX-102 SL - OASIS)

This study is testing if a new medication can help people who have just been in a car accident feel less stressed and prevent long-term trauma symptoms.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: University of North Carolina, Chapel Hill (Academic / other)
• Locations: 9 sites (Birmingham, Alabama and 8 other locations)
• Trial ID: NCT06636786 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of TNX-102 SL, a sublingual formulation of cyclobenzaprine HCl, in reducing symptoms of acute stress reaction (ASR) and preventing post-traumatic stress (PTS) in patients who have experienced a motor vehicle collision. Conducted as a double-blind, placebo-controlled randomized clinical trial, the study will enroll 180 participants who will receive the study drug in the emergency department shortly after their accident. Participants will undergo longitudinal assessments to evaluate psychological and somatic responses over time, aiming to improve neurocognitive function and long-term outcomes related to stress. The trial is part of a broader effort to enhance resilience and performance in both military and civilian populations facing traumatic events.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 55 who have been admitted to the emergency department within 24 hours of a motor vehicle collision and exhibit specific risk factors for post-traumatic stress.

Not a fit: Patients who do not meet the age criteria, have not experienced a motor vehicle collision, or do not exhibit the necessary risk factors for post-traumatic stress may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the incidence and severity of post-traumatic stress symptoms in individuals following traumatic events.

How similar studies have performed: Previous studies involving TNX-102 SL have shown promise in improving sleep quality and reducing symptoms in related conditions, suggesting potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. ≥ 18 years and ≤ 55 years of age
2. Presentation 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. Pain severity in the ED ≥ 4 (0-10 numeric rating scale)
10. People who are not of childbearing potential (e.g., hysterectomy, bilateral oophorectomy, or confirmed postmenopausal for at least last 12 consecutive months)
11. People with the capacity to conceive a pregnancy must agree to employ a highly effective form of birth control throughout the first 21 days of study participation (e.g., oral, injected, transdermal, or implanted hormonal methods of contraception for at least one full menstrual cycle prior to study drug administration; placement of an intrauterine device (IUD) or intrauterine system (IUS); or double barrier methods such as condoms and diaphragms)

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. Any chronic daily opioid use prior to MVC
5. Active psychosis, suicidal ideation, or homicidal ideation
6. Plans for hospital admission
7. History of arrhythmias, heart block or conduction disturbances, congestive heart failure
8. Currently in the acute recovery phase of myocardial infarction
9. Hypersensitivity to cyclobenzaprine or the excipient in TNX-102 SL or placebo formulations
10. History of urinary retention, angle-closure glaucoma, increased intraocular pressure, or hyperthyroidism (TSH \< lower limit of normal)
11. Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation due to risk of potential fatal drug-drug interactions
12. Current or planned use of the following prohibited concomitant medications during study participation: anticholinergic medications, guanethidine, selective serotonin reuptake inhibitors (SSRIs) , serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, MAO inhibitors, anticholinergic medications, guanethidine, potent cytochrome P450 subtype 3A4 inhibitor, St. John's wort, chronic use muscle relaxants or planned use after MCV or other prohibited concomitant medications listed in section 5.6. PI to assess individual cases where single dose of muscle relaxant is prescribed in ED for inclusion
13. Any hepatic impairment or renal disease (defined as AST OR ALT \> 3 times the upper limit of normal) or renal disease (defined as GFR ≤ 80 mL/min)
14. Lacking capacity to provide informed consent (receipt of sedative, hypnotic agent making the patient non-decisional for consent)
15. 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)
16. Elevated baseline blood pressure defined as systolic blood pressure ≥ 170 mmHg or diastolic blood pressure ≥ 100 mmHg and or elevated heart rate of ≥115
17. Abnormal baseline ECG as defined as: QRS duration ≥ 120 ms; QTc \> 460 ms; not in sinus rhythm; or 1st, 2nd, or 3rd degree heart block indicated
18. Substance or alcohol use disorder, bipolar disorder, or schizophrenia
19. History of severe or unexplained oral, or oropharyngeal swelling or edema

Where this trial is running

Birmingham, Alabama and 8 other locations

• University of Alabama at Birmingham — Birmingham, Alabama, United States (Not_yet_recruiting)
• Indiana University — Indianapolis, Indiana, United States (Recruiting)
• University of Kansas Medical Center — Kansas City, Kansas, United States (Recruiting)
• Washington University in St. Louis — St Louis, Missouri, United States (Recruiting)
• Cooper University Health System — Camden, New Jersey, United States (Recruiting)
• The Ohio State University — Columbus, Ohio, United States (Recruiting)
• Rhode Island Hospital — Providence, Rhode Island, United States (Recruiting)
• The Miriam Hospital — Providence, Rhode Island, United States (Recruiting)
• University of Texas Health Science Center at San Antonio — San Antonio, Texas, United States (Not_yet_recruiting)

Study contacts

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

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