Hyperbaric Oxygen Therapy for Traumatic Brain Injury

Overseen By Erik Velasquez

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of South Florida

Must not be taking: Antabuse, Disulfuram, Acetazolamide, others

Disqualifiers: Pregnancy, Bipolar, Schizophrenia, Epilepsy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 44

Duration: 12 weeks

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether hyperbaric oxygen therapy (HBOT) can treat traumatic brain injuries (TBI) in Veterans and active military members. It examines whether HBOT can reduce neurobehavioral and PTSD symptoms and determines the necessary number of sessions. The trial compares HBOT to a placebo (a chamber with normal air) to assess the therapy's effectiveness. Veterans and service members with mild to moderate TBI for over a year who continue to experience symptoms may be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes certain medications that could cause oxygen toxicity, like Antabuse, Disulfuram, Acetazolamide, Sulfamylon, bleomycin, cisplatin, and doxorubicin. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that Hyperbaric Oxygen Therapy is likely to be safe for humans?

Research has shown that Hyperbaric Oxygen Therapy (HBOT) is generally safe for treating traumatic brain injuries. Studies have found that most patients tolerate HBOT well. The most common side effect is mild barotrauma, which feels like a small earache from pressure changes, similar to sensations during airplane takeoffs or landings.

Other research indicates that HBOT can significantly improve thinking and memory problems in people with traumatic brain injuries, suggesting it can enhance brain function without causing major side effects. While some reports show symptom improvement, larger studies are needed to confirm these benefits fully. Overall, current evidence suggests that HBOT is a safe and promising treatment for those with mild to moderate traumatic brain injuries. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for traumatic brain injury, such as medications and rehabilitation therapies, hyperbaric oxygen therapy (HBOT) introduces a unique approach by using a pressurized chamber to deliver 100% oxygen at 2.0 ATA. This method enhances oxygen delivery to the brain, potentially aiding in faster and more effective recovery of damaged brain tissue. Researchers are excited about HBOT because it offers a novel mechanism of action that could complement existing therapies, providing a new hope for improved outcomes in patients with traumatic brain injuries.

What evidence suggests that Hyperbaric Oxygen Therapy might be an effective treatment for traumatic brain injury?

Research has shown that Hyperbaric Oxygen Therapy (HBOT), which participants in this trial may receive, can improve thinking skills in people with traumatic brain injuries (TBI). In one study, more patients with brainstem injuries regained consciousness with HBOT than those without it. Another study found that HBOT improved memory and attention issues compared to pre-treatment levels. However, some studies reported similar improvements in both HBOT and placebo groups, indicating the need for further research. Despite this, early results suggest promising potential for HBOT in aiding TBI patients. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for U.S. Service Members and Veterans aged 18-75 with a history of mild to moderate traumatic brain injury at least one year old, who can consent, tolerate lying down in the HBOT environment for an hour, and speak English. They must have chronic TBI symptoms as indicated by specific test scores.

Inclusion Criteria

I can understand and agree to the study's procedures and risks.

I am a U.S. Service Member or Veteran aged 18-75.

I have chronic symptoms from a brain injury, scoring over 5 on the NSI.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Treatment

Participants undergo 40 sessions of HBOT or placebo over 12 weeks

12 weeks

40 visits (in-person)

Mid-treatment Assessment

Participants complete a mid-treatment assessment after 20 sessions

1 week

1 visit (in-person)

Post-treatment Assessment

Participants complete assessments 2 weeks after the last treatment session

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hyperbaric Oxygen Treatment

Trial Overview The study tests if Hyperbaric Oxygen Therapy (HBOT) reduces neurobehavioral and PTSD symptoms in these individuals compared to a placebo (normal air). It involves attending 40 sessions within 12 weeks and completing assessments before, during, after treatment, and two weeks post-treatment.

How Is the Trial Designed?

Group I: HBOT Group Experimental Treatment 1 Intervention

HBOT chamber pressurized to 2.0 ATA with 100% oxygen

Group II: Placebo/Sham Group Placebo Group 1 Intervention

HBOT chamber that remains unpressurized and has 21% oxygen

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

Approved in United States as Hyperbaric Oxygen Therapy for:

• Carbon monoxide poisoning
• Decompression sickness
• Diabetic foot ulcers
• Wound healing

Approved in European Union as Hyperbaric Oxygen Therapy for:

• Carbon monoxide poisoning
• Decompression sickness
• Diabetic foot ulcers
• Wound healing
• Radiation necrosis

Approved in Canada as Hyperbaric Oxygen Therapy for:

• Carbon monoxide poisoning
• Decompression sickness
• Diabetic foot ulcers
• Wound healing

Who Is Running the Clinical Trial?

University of South Florida

Lead Sponsor

Trials

433

Recruited

198,000+

James A. Haley Veterans' Hospital (JAHVH)

Collaborator

Trials

1

Recruited

420+

Published Research Related to This Trial

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 (HBO) treatment for traumatic brain injury (TBI) may enhance cellular recovery by improving mitochondrial function, rather than just increasing oxygen availability as previously thought.

Administered at 1.5 ATA for 60 minutes, HBO treatment appears to be safe and does not cause oxygen toxicity, suggesting its potential as a therapeutic option for severe brain injuries, although further large-scale studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen in traumatic brain injury. Rockswold, SB., Rockswold, GL., Defillo, A.[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]

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]

Hyperbaric oxygen (HBO) therapy significantly reduces neuronal apoptosis in a mouse model of acute traumatic brain injury (TBI), indicating its potential as a therapeutic intervention.

The mechanism of HBO's protective effect involves the reversal of changes in key proteins associated with apoptosis, specifically through the Akt/GSK3β/β-catenin signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy attenuates neuronal apoptosis induced by traumatic brain injury via Akt/GSK3β/β-catenin pathway. He, H., Li, X., He, Y.[2022]

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 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) 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]

Citations

1. 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 ...

2. neurology.org neurology.org/doi/10.1212/WNL.0000000000211724

A Systematic Review and Meta-analysis (P6-4.001) HBOT significantly improves neurocognitive deficits in traumatic brain injury patients compared to baseline. However, larger trials with ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15241774/

Hyperbaric oxygen therapy for traumatic brain injury In young patients with brainstem contusion, significantly more regained consciousness at 1 month with HBOT (67%) than control (11%) (P<.03). The other found a ...

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

A double-blind randomized trial of hyperbaric oxygen for ... Also, our results suggest 80 HBO2 sessions may be superior to 40 sessions for treatment of long-term brain injury outcomes.

5. 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01306968

Hyperbaric Oxygen Therapy (HBO2) for Persistent Post- ... This is a Phase II randomized trial designed to describe the magnitude of change between baseline and follow-up outcomes for symptom surveys and a battery ...

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

Hyperbaric Oxygen Therapy for Traumatic Brain Injury and/or ... HBOT appears to be well-tolerated by patients with chronic mTBI, with the most common side effect being mild barotrauma. • A targeted review of ...