Hyperbaric Oxygen Therapy for Traumatic Brain Injury

(HOBIT Trial)

Recruiting at 10 trial locations

Overseen By Gaylan L. Rockswold, M.D., Ph.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Hennepin Healthcare Research Institute

Disqualifiers: Pregnant, Pre-existing neurologic disease, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 1 week

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to find the best way to use hyperbaric oxygen treatment for patients with severe brain injuries. The treatment involves breathing pure oxygen at high pressure to help heal the brain. Researchers want to determine the safest and most effective settings for this treatment. Hyperbaric oxygen therapy is an existing and approved treatment for various medical conditions, including decompression sickness, air or gas embolism, and carbon monoxide poisoning.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of 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 might enhance the brain's ability to use oxygen more effectively after treatment, which could lead to better recovery. ^{1 2 3 4 5}

Is hyperbaric oxygen therapy safe for humans?

Hyperbaric oxygen therapy 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, or seizures. These side effects are rare and often depend on individual factors and treatment conditions. ^{3 6 7 8 9}

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 supply to the brain and may help reduce brain damage. Unlike other treatments, HBOT is not a drug and works by creating a high-pressure environment that enhances oxygen delivery to injured brain tissue. ^{1 2 3 4 10}

Research Team

Frederick K Korley, M.D., Ph.D.

Principal Investigator

University of Michigan

Byron Gajewski, Ph.D.

Principal Investigator

University of Kansas Medical Center

Gaylan L Rockswold, M.D., Ph.D.

Principal Investigator

Hennepin County Medical Center, Minneapolis

William Barsan, MD

Principal Investigator

University of Michigan

Eligibility Criteria

This trial is for people aged 16-65 with severe traumatic brain injury (TBI), defined as a Glasgow Coma Scale score of 3 to 8. They must be able to start treatment within 8-14 hours after admission, depending on whether they've had major surgery like craniotomy. Excluded are those who can't start treatment within 24 hours, have non-TBI related coma, penetrating head injuries, pre-existing neurological diseases, unstable spinal cord injury, fixed coagulopathy or severe hypoxia.

Inclusion Criteria

I can start hyperbaric oxygen treatment within 8 hours of admission and don't need major surgery.

My severe brain injury score is between 3 to 8.

I can start hyperbaric oxygen therapy within 14 hours after my brain surgery.

Exclusion Criteria

I have undergone CPR.

My coma is thought to be caused by something other than a brain injury.

I have no health conditions that prevent me from participating in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive hyperbaric oxygen treatment at varying pressures and durations, with or without Normobaric Hyperoxia (NBH), administered twice a day for 5 days

1 week

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including serious adverse events and therapeutic intensity level scores for controlling intracranial pressure

180 days

Treatment Details

Interventions

• Hyperbaric oxygen
• Usual Care

Trial Overview The study tests different hyperbaric oxygen treatments for TBI patients. It aims to find the best combination of pressure levels and normobaric hyperoxia that could improve outcomes in future trials. Treatments vary from usual care to several combinations of hyperbaric oxygen at pressures between 1.5 ATA and 2.5 ATA with or without additional normobaric hyperoxia.

Participant Groups

Group I: Normobaric Hyperoxia (NBH) Experimental Treatment 1 Intervention

Normobaric Hyperoxia (NBH meaning 100% O2 at 1.0 ATA) for 4.5 hours twice a day for 5 days.

Group II: Hyperbaric oxygen (2.5 ATA, no NBH) Experimental Treatment 1 Intervention

Hyperbaric oxygen at 2.5 ATA for 1 hour, without NBH. This treatment is administered twice a day for 5 days.

Group III: Hyperbaric oxygen (2.5 ATA + NBH) Experimental Treatment 1 Intervention

Hyperbaric oxygen at 2.5 ATA for 1 hour and NBH for 3 hours. This treatment is administered twice a day for 5 days.

Group IV: Hyperbaric oxygen (2.0 ATA, no NBH) Experimental Treatment 1 Intervention

Hyperbaric oxygen at 2.0 ATA for 1 hour without NBH. This treatment is administered twice a day for 5 days.

Group V: Hyperbaric oxygen (2.0 ATA + NBH) Experimental Treatment 1 Intervention

Hyperbaric oxygen at 2.0 ATA for 1 hour and NBH for 3 hours. This treatment is administered twice a day for 5 days.

Group VI: Hyperbaric oxygen (1.5 ATA, no NBH) Experimental Treatment 1 Intervention

Hyperbaric oxygen at 1.5 ATA for 1 hour without NBH. This treatment is administered twice a day for 5 days.

Group VII: Hyperbaric oxygen (1.5 ATA + NBH) Experimental Treatment 1 Intervention

Hyperbaric oxygen at 1.5 ATA for 1 hour and NBH for 3 hours. This treatment is administered twice a day for 5 days.

Group VIII: Usual care Active Control 1 Intervention

Usual care for severe TBI

Hyperbaric oxygen is already approved in United States, European Union for the following indications:

Approved in United States as Hyperbaric Oxygen Therapy for:

• Air or gas embolism
• Gas gangrene
• Crush injury
• Compartment syndrome
• Acute peripheral ischemias
• Decompression sickness
• Enhanced healing in selected problem wounds
• Exceptional blood loss anemia
• Necrotizing soft tissue infections
• Osteomyelitis
• Delayed radiation injury (soft tissue and bony necrosis)
• Compromised skin grafts and flaps
• Carbon monoxide poisoning

Approved in European Union as Hyperbaric Oxygen Therapy for:

• Air or gas embolism
• Gas gangrene
• Crush injury
• Compartment syndrome
• Acute peripheral ischemias
• Decompression sickness
• Enhanced healing in selected problem wounds
• Exceptional blood loss anemia
• Necrotizing soft tissue infections
• Osteomyelitis
• Delayed radiation injury (soft tissue and bony necrosis)
• Compromised skin grafts and flaps
• Carbon monoxide poisoning

Who Is Running the Clinical Trial?

Hennepin Healthcare Research Institute

Lead Sponsor

Trials

94

Recruited

77,100+

Strategies to Innovate EmeRgENcy Care Clinical Trials Network

Collaborator

Trials

2

Recruited

710+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN) - Network

Collaborator

Trials

2

Recruited

710+

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]

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) 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 (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]

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 (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]

In a review of 41,273 hyperbaric oxygen therapy sessions involving 3,737 patients over 20 years, the incidence of oxygen toxicity seizures (OTS) was found to be low at 0.06%, indicating that while OTS is a risk, it is relatively rare.

The study revealed that the rate of OTS increases significantly with higher pressures, particularly above 203 kPa, suggesting that pressure levels during treatment should be carefully monitored to minimize the risk of seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen toxicity seizures: 20 years' experience from a single hyperbaric unit. Banham, ND.[2018]

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

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]

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

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

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

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

5. New Zealand pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy attenuates neuronal apoptosis induced by traumatic brain injury via Akt/GSK3β/β-catenin pathway. [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. United States pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen in traumatic brain injury. [2022]

9. Australia pubmed.ncbi.nlm.nih.gov

Oxygen toxicity seizures: 20 years' experience from a single hyperbaric unit. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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