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

40 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Hyperbaric Oxygen Therapy for Traumatic Brain Injury?

Research suggests that Hyperbaric Oxygen Therapy (HBOT) may help improve oxygen supply to the injured brain, potentially reducing brain damage and improving outcomes for patients with traumatic brain injury. Studies indicate that HBOT can enhance the brain's ability to use oxygen more effectively after treatment, which might lead to better recovery. ^{1 2 3 4 5}

Is hyperbaric oxygen therapy safe for humans?

Hyperbaric oxygen therapy (HBOT) is generally considered safe, but some people may experience side effects like ear or sinus pain, anxiety from being in a confined space, low blood sugar, oxygen toxicity, lung collapse, seizures, and shortness of breath. ^{2 5 6 7 8}

How is hyperbaric oxygen therapy different from other treatments for traumatic brain injury?

Hyperbaric oxygen therapy (HBOT) is unique because it involves breathing pure oxygen in a pressurized chamber, which increases oxygen levels in the blood and helps deliver more oxygen to the injured brain, potentially reducing brain damage. Unlike other treatments, HBOT is not a drug and there are no effective medications currently available for traumatic brain injury. ^{1 2 4 5 9}

What is the purpose of this trial?

Mild traumatic brain (mTBI) injury affects 400,000 U.S. Veterans resulting in physical, cognitive and mental health symptoms. The Department of Defense (DoD) reported 26 suicides a day from mTBI despite ongoing care for the Veterans. The purpose of this pilot research study is to evaluate the effect of treating Veterans suffering from mTBI or persistent post-concussion syndrome with hyperbaric oxygen therapy (HBOT).

Research Team

Alison C Bested, MD FRCPC

Principal Investigator

Nova Southeastern University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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]

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 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]

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]

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 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 (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]

References

1. England pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury. [2018]

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

Hyperbaric oxygen therapy for traumatic brain injury: a systematic review of the evidence. [2019]

3. United States 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. [2015]

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

Hyperbaric Oxygen and Outcomes Following the Brain Injury: A Systematic Review. [2023]

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

Immediate and delayed hyperbaric oxygen therapy as a neuroprotective treatment for traumatic brain injury in mice. [2022]

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

A Retrospective Analysis of Adverse Events in Hyperbaric Oxygen Therapy (2012-2015): Lessons Learned From 1.5 Million Treatments. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse effects of hyperbaric oxygen therapy: a systematic review and meta-analysis. [2023]

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

Seizure during hyperbaric oxygen therapy: experience at a single academic hospital in Korea. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Biochemical response to hyperbaric oxygen treatment of a transhemispheric penetrating cerebral gunshot injury. [2020]