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: Gaylan Rockswold

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores different ways to use hyperbaric oxygen therapy for severe traumatic brain injuries (TBI). Participants will receive varying levels of oxygen treatment to determine the most effective approach for future studies. It targets individuals who have experienced a severe TBI and can begin treatment soon after their injury. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that hyperbaric oxygen therapy (HBOT) is usually safe at specific pressure levels. Studies have found that using HBOT at 1.5 ATA (a measure of pressure) is safe for individuals with traumatic brain injuries. At this level, the therapy typically avoids causing oxygen toxicity, which can occur with excessive oxygen.

However, when the chamber pressure exceeds 2.0 ATA, the risk of side effects increases, potentially causing ear discomfort or sinus problems. Therefore, careful monitoring is crucial to maintain safety.

For normobaric hyperoxia (NBH), which involves breathing pure oxygen at normal air pressure, studies suggest it is generally safe and may be easier to implement in medical settings. Both HBOT and NBH have shown potential in aiding brain injuries, but they require careful use to prevent complications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about hyperbaric oxygen therapy for traumatic brain injury (TBI) because it offers a unique approach compared to standard care options like medication and rehabilitation therapies. Unlike typical treatments, hyperbaric oxygen therapy involves breathing pure oxygen in a pressurized chamber, which can enhance the body's natural healing process by increasing oxygen delivery to injured brain tissues. This method has the potential to reduce inflammation and promote brain repair more effectively. Additionally, the therapy's rapid treatment schedule—twice daily sessions over just five days—could lead to quicker improvements in patients with severe TBI. The use of different oxygen pressures and durations, as well as the combination with normobaric hyperoxia, provides various experimental approaches to optimize recovery.

What evidence suggests that this trial's treatments could be effective for traumatic brain injury?

Research shows that hyperbaric oxygen therapy (HBOT) can help treat traumatic brain injury (TBI). In this trial, participants may receive HBOT at different pressures: 1.5 atmosphere absolute (ATA), 2.0 ATA, or 2.5 ATA. HBOT at 1.5 ATA has improved symptoms and thinking abilities in TBI patients. Studies on HBOT at 2.0 ATA have shown better blood flow in the brain and improved thinking, especially for post-concussion symptoms. Additionally, evidence suggests that HBOT at 2.5 ATA can lower the risk of death and aid recovery in moderate to severe TBI cases. Another treatment option in this trial is breathing 100% oxygen at normal pressure, known as normobaric hyperoxia (NBH), which has improved thinking by addressing low oxygen levels in the brain. These treatments aim to increase oxygen in the brain, potentially aiding recovery and brain function. ^{1 6 7 8 9}

Who Is on the Research Team?

Byron Gajewski, Ph.D.

Principal Investigator

University of Kansas Medical Center

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

Principal Investigator

University of Michigan

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

Principal Investigator

Hennepin County Medical Center, Minneapolis

William Barsan, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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?

Gaylan Rockswold

Lead Sponsor

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+

Published Research Related to This Trial

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]

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 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) 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]

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 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]

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]

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.

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 ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35370898/

Hyperbaric Oxygen Therapy Efficacy in Mild Traumatic ...

Conclusion: In multiple randomized and randomized controlled studies HBOT at 1.5 ATA oxygen demonstrated statistically significant symptomatic ...

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.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02089594

NCT02089594 | Hyperbaric Oxygen Treatment to Treat ...

An eight-week course of forty low-pressure Hyperbaric Oxygen Treatment's (HBOT's) can significantly improve symptoms and cognitive function in subjects with ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10232961/

Adverse effects of hyperbaric oxygen therapy - PubMed Central

Hyperbaric oxygen therapy (HBOT) is more likely to cause adverse reactions when the chamber pressure is above 2.0 ATA.

7.

hsrd.research.va.gov

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

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

Those using HBOT at 1.5 ATA45-47 delivered the therapy in 1-hour sessions spaced 4 to 24 hours apart for as few as 3 days and as long as 2 weeks ...

8.

frontiersin.org

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

Hyperbaric Oxygen Therapy Efficacy in Mild Traumatic ...

Conclusion: In multiple randomized and randomized controlled studies HBOT at 1.5 ATA oxygen demonstrated statistically significant symptomatic and cognitive or ...

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02407028

Hyperbaric Oxygen Brain Injury Treatment Trial (HOBIT)

Clinical investigators have used pressure varying from 1.5 to 2.5 ATA. However, the lungs in severe TBI patients have frequently been compromised by direct lung ...