Hyperbaric Oxygen Therapy for Traumatic Brain Injury

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Nova Southeastern University

Must not be taking: Steroids, Immunosuppressants, Bleomycin, Doxorubicin

Disqualifiers: Female, Major depression, Schizophrenia, Alcoholism, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether hyperbaric oxygen therapy (breathing pure oxygen in a pressurized room) can benefit U.S. Veterans with mild traumatic brain injuries by improving their mental health. The therapy involves 40 sessions over a few weeks to determine if it reduces symptoms like confusion or memory loss. Veterans who have experienced mild brain injuries, such as brief memory loss or loss of consciousness, may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using medications that affect immune function, like steroids or immunosuppressants, you may not be eligible to participate.

What prior data suggests that hyperbaric oxygen therapy is safe for treating mild traumatic brain injury?

Research has shown that Hyperbaric Oxygen Therapy (HBOT) is generally safe for treating mild traumatic brain injury (mTBI). Studies have found that HBOT, at a pressure level of 1.5 times the normal atmospheric pressure, is well-tolerated and can help manage long-term problems related to brain injuries. A common side effect is mild barotrauma, a minor injury to the ear or sinuses caused by pressure changes, similar to what some people feel during air travel.

One study highlighted that HBOT can significantly improve thinking and memory skills for those with post-concussion syndrome. Although some results suggest HBOT is not always more effective than a placebo, it remains a relatively safe option for people with brain injuries. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Hyperbaric Oxygen Therapy (HBOT) is unique because it delivers pure oxygen at higher-than-normal pressure levels, which can enhance brain healing. Unlike standard treatments for mild traumatic brain injury that typically focus on symptom management with medications and cognitive therapies, HBOT may promote actual tissue repair and recovery. Researchers are excited because HBOT could potentially offer faster and more effective relief by improving oxygen supply to injured brain areas, possibly reducing inflammation and aiding in cellular repair.

What evidence suggests that hyperbaric oxygen therapy might be an effective treatment for mild traumatic brain injury?

Research suggests that hyperbaric oxygen therapy (HBOT) might benefit individuals with traumatic brain injuries (TBIs). Some studies have found that HBOT can increase oxygen flow to the brain, potentially aiding recovery. However, results for mild TBI remain mixed. In one study, participants showed improvement, but it was not significantly better than a placebo. Another study found some symptom relief with HBOT, but it was less effective than an alternative treatment. While HBOT appears promising, more research is needed to determine its effectiveness for mild TBI. This trial will provide HBOT to evaluate its effectiveness specifically for mild TBI in U.S. Veterans. ^{1 4 6 7 8}

Who Is on the Research Team?

Alison C Bested, MD FRCPC

Principal Investigator

Nova Southeastern University

Are You a Good Fit for This Trial?

This trial is for U.S. Veterans who have mild traumatic brain injuries (mTBI) or persistent post-concussion symptoms. It's aimed at those experiencing physical, cognitive, or mental health issues due to their injury.

Inclusion Criteria

I am a male U.S. Veteran with a mild brain injury but was in good health before.

Exclusion Criteria

My fatigue is not explained by any other diagnosed conditions.

I do not have chronic infections like HIV or hepatitis.

My liver is not working properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hyperbaric oxygen therapy (HBOT) at 1.5 atmospheres absolute (ATA) for a dive time of 60 minutes, twice a day Monday through Friday, for a total of 40 treatments.

4 weeks

Daily visits (in-person) Monday through Friday

Follow-up

Participants are monitored for safety and effectiveness after treatment with online questionnaires and various assessments at 1, 6, and 12 months post-HBOT.

12 months

Online assessments at 1, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Hyperbaric Oxygen Therapy

Trial Overview

The study tests the effects of hyperbaric oxygen therapy (HBOT), where participants breathe pure oxygen in a pressurized chamber. The goal is to see if this treatment can improve symptoms from mTBI.

How Is the Trial Designed?

Group I: Treatment of U.S. Veterans with mild traumatic brain injury with hyperbaric oxygen therapy Experimental Treatment 2 Interventions

Pilot Study - A total of 40 HBOT treatments at 1.5 atmospheres absolute (ATA) for a dive time of 60 minutes, twice a day Monday through Friday. The treatments were separated by an air break of 4 hours on the same day. Measurements of the effectiveness of HBOT in mTBI done before and after HBOT.

Hyperbaric Oxygen Therapy is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Hyperbaric Oxygen Therapy for:

• Decompression sickness
• Gas gangrene
• Carbon monoxide poisoning
• Wound healing
• Radiation injury

Approved in European Union as Hyperbaric Oxygen Therapy for:

• Decompression sickness
• Gas gangrene
• Carbon monoxide poisoning
• Wound healing
• Radiation injury
• Diabetic foot ulcers

Approved in Canada as Hyperbaric Oxygen Therapy for:

• Decompression sickness
• Gas gangrene
• Carbon monoxide poisoning
• Wound healing
• Radiation injury

Approved in Japan as Hyperbaric Oxygen Therapy for:

• Decompression sickness
• Gas gangrene
• Carbon monoxide poisoning
• Wound healing

Who Is Running the Clinical Trial?

Nova Southeastern University

Lead Sponsor

Trials

103

Recruited

12,000+

Published Research Related to This Trial

Hyperbaric oxygen (HBO) therapy may help improve biochemical parameters in patients with traumatic brain injuries, as demonstrated in a case report of a 23-year-old man with a severe gunshot wound.

The study suggests that HBO therapy could be a beneficial treatment option to reduce secondary complications following traumatic brain injury, although further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical response to hyperbaric oxygen treatment of a transhemispheric penetrating cerebral gunshot injury. Thelin, EP., Bellander, BM., Nekludov, M.[2020]

In a review of over 1.5 million hyperbaric oxygen therapy treatments, only 0.68% were linked to adverse events, indicating that serious complications are rare.

The most common issues reported were barotrauma and confinement anxiety, while severe events like oxygen toxicity occurred in less than 0.05 per 1000 treatments, suggesting that HBO therapy is a safe and low-risk treatment when following proper protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Analysis of Adverse Events in Hyperbaric Oxygen Therapy (2012-2015): Lessons Learned From 1.5 Million Treatments. Jokinen-Gordon, H., Barry, RC., Watson, B., et al.[2022]

In a study involving 42 patients with severe traumatic brain injury, the combination of hyperbaric oxygen (HBO2) and normobaric hyperoxia (NBH) significantly increased brain tissue oxygen levels and improved markers of cerebral metabolism compared to standard care.

The combined HBO2/NBH treatment resulted in a 26% reduction in mortality and a 36% improvement in favorable outcomes, indicating its potential as an effective therapeutic strategy for severe TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury. Rockswold, SB., Rockswold, GL., Zaun, DA., et al.[2015]

In a study of 1,308 patients receiving hyperbaric oxygen (HBO2) therapy, five seizure episodes were reported during 10,425 treatments, indicating a low but notable risk of seizures, particularly in patients with carbon monoxide poisoning and arterial gas embolism.

Despite the occurrence of seizures, none of the patients experienced lasting effects, suggesting that while seizures can happen during HBO2 therapy, the overall safety profile remains high, and clinicians should be prepared to manage such events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizure during hyperbaric oxygen therapy: experience at a single academic hospital in Korea. Lee, CH., Choi, JG., Lee, JS., et al.[2021]

Hyperbaric oxygen therapy (HBOT) may offer a potential mortality benefit for certain subgroups of traumatic brain injury (TBI) patients, as one study showed a decrease in mortality from 31% in controls to 17% in the HBOT group, although results were conflicting across studies.

Adverse events associated with HBOT, such as seizures and pulmonary symptoms, were reported, but the overall evidence regarding its effectiveness and safety remains insufficient, highlighting the need for more high-quality research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy for traumatic brain injury: a systematic review of the evidence. McDonagh, M., Helfand, M., Carson, S., et al.[2019]

Hyperbaric oxygen therapy (HBOT) administered after moderate traumatic brain injury (mTBI) significantly improved cognitive function in mice, showing similar performance to control (sham) groups, indicating its potential efficacy as a treatment.

Both immediate and delayed HBOT treatments (administered 3 hours and 7 days post-injury, respectively) prevented neuronal loss and other negative biochemical changes associated with mTBI, suggesting a long therapeutic window for neuroprotection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate and delayed hyperbaric oxygen therapy as a neuroprotective treatment for traumatic brain injury in mice. Baratz-Goldstein, R., Toussia-Cohen, S., Elpaz, A., et al.[2022]

Hyperbaric oxygen therapy (HBOT) significantly reduced the risk of death in patients with traumatic brain injury, with a relative risk of 0.69, indicating that treating seven patients with HBOT could prevent one additional death.

However, HBOT did not show a significant improvement in favorable clinical outcomes, suggesting that while it may help with survival, it does not necessarily lead to better recovery or quality of life for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury. Bennett, MH., Trytko, B., Jonker, B.[2018]

Hyperbaric oxygen therapy (HBOT) is associated with a higher incidence of adverse effects (30.11%) compared to control groups (10.43%), particularly when the treatment involves more than 10 sessions or chamber pressures exceed 2.0 ATA.

The most common side effect reported was ear discomfort, indicating that while HBOT can be beneficial, careful monitoring for adverse reactions is necessary, especially under specific conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of hyperbaric oxygen therapy: a systematic review and meta-analysis. Zhang, Y., Zhou, Y., Jia, Y., et al.[2023]

Citations

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esmed.org

esmed.org/MRA/mra/article/view/4161

The Efficacy of Hyperbaric Oxygen Therapy in Traumatic ...

Hyperbaric oxygen therapy may be recommended in acute moderate-severe traumatic brain injury patients (Type 2a recommendation, level A evidence).

2.

nature.com

nature.com/articles/s41598-025-86631-6

A double-blind randomized trial of hyperbaric oxygen for ...

Prior trials of HBO2 show encouraging results for improvement of sequelae months to years after traumatic brain injury (TBI), stroke, and long ...

3.

frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.815056/full

Hyperbaric Oxygen Therapy Efficacy in Mild Traumatic ...

The authors found 6-week post-treatment symptom reductions (improvements) of 13% in the HBOT group and 41% in the 1.3 ATA air group with 10 subtests improved on ...

4.

hsrd.research.va.gov

hsrd.research.va.gov/publications/esp/hbot-brief.pdf

Hyperbaric Oxygen Therapy for Traumatic Brain Injury and/or ...

Evidence from case series suggesting that. HBOT may lead to improved cerebral blood flow, PTSD and post- concussion symptoms, and patient ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5426690/

Is Hyperbaric Oxygen Therapy Effective for Traumatic Brain ...

For mild TBI, results indicate HBO2 is no better than sham treatment. Improvements within both HBO2 and sham groups cannot be ignored. For acute treatment of ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01306968

Hyperbaric Oxygen Therapy (HBO2) for Persistent Post- ...

If HBO2, which is regularly available and relatively safe, improves outcome in brain-injured subjects by treating the underlying pathophysiology of post- ...

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S187887502300699X

Hyperbaric Oxygen Therapy for the Management of Mild ...

HBOT using 1.5 atmosphere absolute in increments of 40 sessions was found to be a safe and effective modality in the management of the long-term sequelae of TBI ...

8.

frontiersin.org

frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1641033/full

Hyperbaric oxygen therapy improves post-concussion ...

This study provides initial evidence that HBOT can elicit significant cognitive improvements in adults with chronic PCS from childhood TBI.