Cyclobenzaprine for Post-Traumatic Stress Disorder

(OASIS Trial)

Recruiting at 5 trial locations

Overseen By Chad Cannon, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Antidepressants, Anticholinergics, Opioids, others

Disqualifiers: Pregnancy, Heart conditions, Substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

180 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes participants using specific medications like SSRIs, SNRIs, TCAs, and others listed in the protocol. If you're taking any of these, you might need to stop them before joining the trial.

What data supports the effectiveness of the drug Cyclobenzaprine for treating PTSD?

A study found that a higher dose of Cyclobenzaprine (5.6 mg) taken at bedtime showed some improvement in PTSD symptoms compared to a placebo, particularly in overall improvement and social functioning. Additionally, early improvements in sleep were linked to better PTSD outcomes after 12 weeks. ^{1 2 3 4 5}

How is the drug cyclobenzaprine unique for treating PTSD?

Cyclobenzaprine, used in a sublingual form called TNX-102 SL, is unique for PTSD treatment because it focuses on improving sleep quality, which is linked to better PTSD outcomes. This approach is different from other treatments that primarily target neurotransmitter systems like norepinephrine or serotonin. ^{2 3 5 6 7}

What is the purpose of this trial?

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.

Research Team

Samuel McLean, MD

Principal Investigator

University of North Carollina at Chapel Hill

Christopher Jones, MD

Principal Investigator

Cooper University Health Care

Eligibility Criteria

This trial is for individuals who have recently been in a motor vehicle collision and are at high risk of developing acute stress reactions or disorders. Participants will receive treatment shortly after the event and must be willing to undergo assessments over several weeks.

Inclusion Criteria

Able to speak and read English

I am willing and able to follow all study rules and attend all appointments.

PTS prediction tool risk score ≥ 16 in the ED

Exclusion Criteria

I am scheduled to be admitted to the hospital.

I have a serious injury, like a major bone break.

I am currently recovering from a recent heart attack.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive TNX-102 SL or placebo in the ED and continue treatment for 2 weeks

2 weeks

1 visit (in-person) in ED, daily self-administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Multiple assessments at Week 1, 3, 6, 12

Long-term follow-up

Participants are assessed for long-term outcomes such as PTSD and depressive symptoms

12 weeks

Treatment Details

Interventions

• Cyclobenzaprine HCl

Trial Overview The study tests if TNX-102 SL, taken sublingually, can reduce symptoms of acute stress reaction/disorder right after a traumatic event like a car crash. It's compared with a placebo in a double-blind setup where neither doctors nor patients know who gets the real medicine.

Participant Groups

Group I: Cyclobenzaprine HCl Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Mclean Hospital

Collaborator

Trials

221

Recruited

22,500+

Cooper University Health Care

Collaborator

Trials

2

Recruited

2,000+

Tonix Pharmaceuticals, Inc.

Industry Sponsor

Trials

31

Recruited

4,900+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Current pharmacologic treatments for PTSD, such as antidepressants and anxiolytics, are based on drugs developed for other conditions, highlighting a need for more targeted therapies.

Future drug development for PTSD may focus on novel classes of compounds that directly address the disorder's unique biological mechanisms, including corticotropin-releasing factor antagonists and neuropeptide Y enhancers, which could lead to more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What might the psychobiology of posttraumatic stress disorder teach us about future approaches to pharmacotherapy? Friedman, MJ.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of posttraumatic stress disorder: the impact of paroxetine. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of bedtime sublingual cyclobenzaprine (TNX-102 SL) in military-related PTSD and the role of sleep quality in treatment response. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

The alpha1-adrenergic antagonist prazosin ameliorates combat trauma nightmares in veterans with posttraumatic stress disorder: a report of 4 cases. [2019]

4. England pubmed.ncbi.nlm.nih.gov

The use of stimulants in the treatment of post traumatic stress disorder: case report. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

What might the psychobiology of posttraumatic stress disorder teach us about future approaches to pharmacotherapy? [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Noradrenergic and serotonergic function in posttraumatic stress disorder. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder. [2021]