Recruiting
Phase 2

Sublingual Cyclobenzaprine

Sponsor:

University of North Carolina, Chapel Hill

Code:

NCT06636786

Conditions

Acute Stress Reaction

Acute Stress Disorder

Neurocognitive Function

Post-traumatic Stress

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Interventions

Cyclobenzaprine HCl

Placebo

Study Details

Brief summary:

This study will examine the safety and efficacy of TNX-102 SL 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 Optimizing Acute Stress reaction Interventions with TNX-102 SL (OASIS) Trial, a double-blind placebo-controlled randomized clinical trial (RCT) to determine if TNX-102 SL initiated in the ED in the hours after MVC to high risk individuals, treats/reduces acute stress reaction (ASR)/acute stress disorder (ASD) symptoms (primary outcome), improves neurocognitive function, and prevents/reduces posttraumatic stress (PTS) symptoms (secondary outcomes) long term. 180 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.

Conditions

Acute Stress Reaction

Acute Stress Disorder

Neurocognitive Function

Post-traumatic Stress

Study ID

NCT06636786

Start date

Mar 25, 2025

Status verified date

Aug, 2026

Completion date

Sep, 2026

Anticipated

Primary completion date

Sep, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 55

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. ≥ 18 years and ≤ 55 years of age
2. Presentation to ED and able to complete enrollment visit activities 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 28 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. In addition to the lab results in exclusion #13 above, exclude patients who report the following and or if the following are in medical records -

  • history of renal disease
  • history of urinary retention, angle-closure glaucoma, increased intraocular pressure, or hyperthyroidism
15. As part of additional screening, exclude patients who answer yes to any of the questions listed below-

  • Have you ever been told that you have renal or kidney disease?
  • Have you ever been diagnosed with hyperthyroidism or active overactive thyroid?
  • Have ever been told that you have a liver disease or cirrhosis, or problems with your liver?
16. Any history of seizure disorder
17. Lacking capacity to provide informed consent (receipt of sedative, hypnotic agent making the patient non-decisional for consent)
18. 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)
19. Elevated baseline blood pressure defined as systolic blood pressure ≥ 170 mmHg or diastolic blood pressure ≥ 100 mmHg and or elevated heart rate of ≥115
20. 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
21. Substance or alcohol use disorder, bipolar disorder, or schizophrenia
22. History of severe or unexplained oral, or oropharyngeal swelling or edema
23. History of presyncope or syncopal episodes

Study Design

Enrollment

180 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: Cyclobenzaprine HCl

Participants will be instructed to take a half dose (equivalent to 1 tablet, 2.8 mg) of Cyclobenzaprine HCl in the ED as part of enrollment procedures. If the time between the first half dose and the planned bedtime of the participant is less than 6 hours, participants will be instructed to take 1 tablet (half dose) the first night at bedtime. If the time between the first half dose and planned bedtime of the participant is greater than or equal to 6 hours, then participants will be instructed to take a full dose (equivalent to 2 tablets) the first night. Over the following 13 days, all participants will be instructed to take a full dose of the study drug at bedtime. Each participant will receive 29 tablets and take either 28 or 29 tablets total for the duration of study participation.

placebo comparator: Placebo

Participants will be instructed to take a half dose (equivalent to 1 tablet, 2.8 mg) of placebo in the ED as part of enrollment procedures. The placebo is the same formulation as active except the Cyclobenzaprine HCl content is replaced by Mannitol to maintain the same tablet weight and dimensions. If the time between the first half dose and the planned bedtime of the participant is less than 6 hours, participants will be instructed to take 1 tablet (half dose) the first night at bedtime. If the time between the first half dose and planned bedtime of the participant is greater than or equal to 6 hours, then participants will be instructed to take a full dose (equivalent to 2 tablets) the first night. Over the following 13 days, all participants will be instructed to take a full dose of the study drug at bedtime. Each participant will receive 29 tablets and take either 28 or 29 tablets total for the duration of study participation.

Interventions

Cyclobenzaprine HCl

TNX-102 SL (cyclobenzaprine HCl sublingual tablets) taken sublingually (under the tongue) in the ED and each day at bedtime for a total of 2 weeks.

Placebo

Placebo sublingual tablets taken sublingually (under the tongue) in the ED and each day at bedtime for a total of 2 weeks.

Primary outcome measure

  • Change in ASD Score [ Time Frame: Week 1, 3 after MVC ]

Central Contacts and Locations

Central contacts

Locations

Indiana University

Recruiting

Indianapolis, Indiana, United States, 46202

Contacts

Principal Investigator:

Paul Musey, MD

University of Kansas Medical Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Principal Investigator:

Lindsay Maguire, MD

Washington University in St. Louis

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Principal Investigator:

Stacey House, MD

Cooper University Health System

Recruiting

Camden, New Jersey, United States, 08103

Principal Investigator:

Christopher Jones

The Ohio State University

Recruiting

Columbus, Ohio, United States, 43210

Principal Investigator:

Michael Lyons

Rhode Island Hospital

Recruiting

Providence, Rhode Island, United States, 02903

Contacts

Principal Investigator:

Adam Aluisio, MD

The Miriam Hospital

Recruiting

Providence, Rhode Island, United States, 02903

Contacts

Principal Investigator:

Adam Aluisio, MD

University of Texas Health Science Center at San Antonio

Recruiting

San Antonio, Texas, United States, 78229

Principal Investigator:

Ralph Riviello

More Information

Sponsor

University of North Carolina, Chapel Hill

Last update posted

Sep 1, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of North Carolina, Chapel Hill on 2026-09-01.