Cyclobenzaprine for Post-Traumatic Stress Disorder

(OASIS Trial)

Recruiting at 6 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of Cyclobenzaprine HCl, a muscle relaxant, in reducing stress symptoms after a car crash. Researchers aim to determine if taking this treatment shortly after the incident decreases immediate stress reactions and long-term post-traumatic stress symptoms. Participants will take either the study medication or a placebo over two weeks to evaluate these effects. This trial suits individuals who have visited the emergency room after a car accident and are returning home, particularly those with significant pain and a high risk for stress disorders. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that TNX-102 SL, a form of cyclobenzaprine taken under the tongue, is generally well-tolerated. In earlier studies, most patients did not experience serious side effects. Common side effects included drowsiness and dry mouth, typical for this type of medication. Evidence also indicates that it helps improve sleep and reduce symptoms of stress disorders. This treatment is under study for conditions like PTSD and fibromyalgia. Although this trial remains in the early stages, its testing indicates it has passed initial safety checks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Unlike most treatments for PTSD, which typically involve psychotherapy and medications like SSRIs or SNRIs, Cyclobenzaprine HCl is a muscle relaxant that offers a new approach by potentially addressing the condition through its effects on sleep and muscle tension. Researchers are excited about this treatment because it may provide faster relief of PTSD symptoms, potentially improving sleep quality, which is often disrupted in PTSD patients. Cyclobenzaprine's unique mechanism of targeting both muscle relaxation and sedation could complement existing therapies, offering a novel avenue for managing symptoms more effectively.

What evidence suggests that Cyclobenzaprine HCl might be an effective treatment for acute stress reaction?

Research has shown that Cyclobenzaprine HCl, particularly in the form TNX-102 SL, might aid conditions like PTSD by improving sleep problems. In this trial, participants will receive either Cyclobenzaprine HCl or a placebo. One study found that a higher dose of Cyclobenzaprine (5.6 mg) at bedtime improved PTSD symptoms more than a placebo, especially in sleep and social interactions. This suggests it could also help reduce immediate stress reactions and prevent long-term stress after traumatic events. Early findings indicate the treatment is well-tolerated and may support recovery by addressing sleep issues, which are often a major component of stress disorders. ^{1 2 6 7 8}

Who Is on the Research Team?

Samuel McLean, MD

Principal Investigator

University of North Carollina at Chapel Hill

Christopher Jones, MD

Principal Investigator

Cooper University Health Care

Are You a Good Fit for This Trial?

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

PTS prediction tool risk score ≥ 16 in the ED

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/pii/S0165178124000490

A phase 3, randomized, placebo-controlled, trial to ...

This study provides preliminary evidence that TNX-102 SL is well-tolerated and may promote recovery from PTSD by addressing sleep-related symptoms.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06636786

NCT06636786 | Prevention/Reduction of ASRs and PTSD ...

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 ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/33979763/

Randomized clinical trial of bedtime sublingual ...

This provides preliminary evidence that TNX-102 SL 5.6 mg reduces PTSD symptoms, improves sleep and psychosocial function, and is well tolerated.

4.

withpower.com

withpower.com/trial/cyclobenzaprine-for-post-traumatic-stress-disorder-d07a1

Cyclobenzaprine for Post-Traumatic Stress Disorder

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 ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0165178121002717

Randomized clinical trial of bedtime sublingual ...

I · Sublingual cyclobenzaprine 5.6 mg for 12 weeks nominally reduced PTSD severity over placebo · Improvement in sleep and psychosocial function also observed.

6.

medicine.iu.edu

medicine.iu.edu/emergency-medicine/research/clinical/asr-ptsd-sublingual-cyclobenzaprine-hci

Prevention/​Reduction of ASRs and PTSD to Sustain Civilian ...

TNX-102 SL (cyclobenzaprine HCl sublingual tablet) is being developed for the management of fibromyalgia (FM) and post-traumatic stress disorder (PTSD) by Tonix ...

7.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK513362/

Cyclobenzaprine - StatPearls - NCBI Bookshelf - NIH

A recent randomized controlled trial indicates that sublingual cyclobenzaprine decreases posttraumatic stress disorder(PTSD) symptoms and improves sleep and ...

8.

tonixpharma.com

tonixpharma.com/wp-content/uploads/2024/08/MHSRS-2024-Two-Clinical-Trials-of-Bedtime-Sublingual-Cyclobenzaprine.pdf

Two Clinical Trials of Bedtime Sublingual Cyclobenzaprine ...

Data from these trials support testing of a two-week course of TNX beginning within 24 hours of index trauma for effects on acute stress reaction (ASR) ...