Hyperbaric Oxygen Therapy for Post-Concussion Syndrome

(HOINPCS Trial)

Overseen By Olayinka D Ajayi, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Essentia Health

Disqualifiers: Pregnancy, Psychotic disorders, Severe TBI, 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

Compensation: Varies

Number of Visits: 41

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if hyperbaric oxygen therapy can help individuals with persistent symptoms following a mild concussion, such as headaches, dizziness, or trouble concentrating. Participants will receive either the actual hyperbaric oxygen therapy or a placebo treatment to assess any differences. Individuals who have experienced a mild concussion in the past 3 months to 5 years and continue to have these symptoms may be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Do I need to stop my current medications for the trial?

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 generally safe, even at a pressure level of 1.5 times normal atmospheric pressure used in some treatments. Studies have found that patients with mild traumatic brain injury, including those with ongoing post-concussion symptoms, tolerate this therapy well. While effectiveness can vary, safety is typically not a major concern. Most people do not experience serious side effects when receiving HBOT for these conditions. The therapy involves breathing pure oxygen in a pressurized room, which most participants find manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Hyperbaric Oxygen Therapy (HBO) for post-concussion syndrome is unique because it delivers high levels of oxygen under increased atmospheric pressure. Unlike standard treatments for post-concussion syndrome, which typically involve medications for symptom relief, cognitive therapy, and rest, HBO targets the condition by enhancing oxygen delivery to the brain, potentially promoting faster healing of damaged tissues. Researchers are excited about this approach because it could offer a more direct and potentially quicker recovery path for individuals suffering from lingering concussion symptoms.

What evidence suggests that hyperbaric oxygen therapy might be an effective treatment for post-concussion syndrome?

This trial will compare hyperbaric oxygen therapy (HBOT) with a sham control treatment for individuals with post-concussion syndrome. Research has shown that HBOT can significantly help people with ongoing symptoms after a concussion. One study found that HBOT improved both concussion and PTSD symptoms. Another study demonstrated that HBOT can enhance thinking skills in adults with long-term symptoms from childhood head injuries. By increasing oxygen levels in the blood, this therapy aids in healing damaged brain tissue. These findings suggest that HBOT could be a promising option for those with lasting symptoms after a concussion. ^{1 2 4 6 7}

Who Is on the Research Team?

Olayinka D Ajayi, MD, MPH

Principal Investigator

Essentia Health

Marc Basson, MD, PhD

Principal Investigator

University of North Dakota

Marilyn Klug, PhD

Principal Investigator

University of North Dakota

Paulina Kunecka, MD

Principal Investigator

Essentia Health

Richard Ferraro, PhD

Principal Investigator

University of North Dakota

Rebecca Quinn, MSW, LMSW

Principal Investigator

Center for Rural Health, University of North Dakota

Sharon Hanson, RN

Principal Investigator

Essentia Health

Are You a Good Fit for This Trial?

Adults who've had a mild traumatic brain injury between 3 months to 5 years ago and are experiencing ongoing symptoms like headaches or dizziness. They must be able to speak English, give informed consent, follow the study plan, and provide blood samples. Excluded are pregnant women, prisoners, minors, those with severe TBIs or certain medical conditions that prevent safe hyperbaric treatment.

Inclusion Criteria

Willing and able to provide informed consent

I had a mild head injury between 3 months and 5 years ago.

My brain injury was caused by a blow to the head, not by something going through my skull.

Exclusion Criteria

People who work in or use hyperbaric chambers, or engage in SCUBA diving.

You cannot protect your airway or need frequent suctioning.

I have had hyperbaric oxygen treatment before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive hyperbaric oxygen or sham treatment for 60 minutes per session, 5 sessions per week for 3 months

12 weeks

40 visits (in-person)

Follow-up

Participants are monitored for changes in neuropsychological status and other outcomes

18 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Hyperbaric Oxygen
• Sham treatment

Trial Overview The trial is testing if breathing pure oxygen in a pressurized chamber (hyperbaric oxygen at 1.5 ATA) can help improve brain function after concussion compared to a sham (fake) treatment. Participants will be randomly assigned to one of these two treatments.

How Is the Trial Designed?

Group I: HBO at 1.5 Atmosphere absolute Experimental Treatment 1 Intervention

Participants in this group will be exposed to hyperbaric oxygen at 1.5 atmosphere absolute (ATA) for 60 minutes per session. Each participant will complete 40 sessions, five sessions per week within 3 months from randomization

Group II: Sham control initially at 1.2 then changed to 1.0 ATA Placebo Group 1 Intervention

Participants in this group will be exposed to hyperbaric oxygen at 1.2 atmosphere absolute (ATA) during the first 5 to 7 minutes and the chamber pressure will be reduced to 1.0 ATA for the remaining 53 - 57 minutes for a total of 60 minutes per session. Each participant will complete 40 sessions, five sessions per week within 3 months from randomization

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

Approved in United States as HBOT for:

• Air or Gas Embolism
• Carbon Monoxide Poisoning
• Central Retinal Artery Occlusion
• Decompression Sickness
• Gas Gangrene
• Idiopathic Sudden Sensorineural Hearing Loss
• Progressive Necrotizing Soft Tissue Infections

Approved in European Union as HBOT for:

• Air or Gas Embolism
• Carbon Monoxide Poisoning
• Central Retinal Artery Occlusion
• Decompression Sickness
• Gas Gangrene
• Idiopathic Sudden Sensorineural Hearing Loss
• Progressive Necrotizing Soft Tissue Infections

Who Is Running the Clinical Trial?

Essentia Health

Lead Sponsor

Trials

27

Recruited

107,000+

University of North Dakota

Collaborator

Trials

17

Recruited

1,200+

Dakota Medical Foundation

Collaborator

Trials

1

Recruited

40+

The Swanson Foundation

Collaborator

Trials

1

Recruited

40+

State of North Dakota

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

In a study involving 16 military subjects with chronic blast-induced mild to moderate traumatic brain injury and PTSD, 40 sessions of 1.5 ATA hyperbaric oxygen therapy (HBOT) over 30 days were found to be safe, with only minor reversible side effects reported.

Post-treatment assessments showed significant improvements in cognitive function, PTSD and PCS symptoms, and overall quality of life, indicating that HBOT may be an effective intervention for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of low-pressure hyperbaric oxygen therapy for blast-induced post-concussion syndrome and post-traumatic stress disorder. Harch, PG., Andrews, SR., Fogarty, EF., et al.[2021]

Hyperbaric oxygen therapy (HBOT) has shown promise in treating acute and severe traumatic brain injuries, but its effectiveness for post concussion syndrome (PCS) remains uncertain due to various limitations in existing studies.

Key issues identified in the studies include the use of inappropriate control groups, delayed treatment administration, reliance on subjective assessment methods, and small sample sizes, which may affect the reliability of the findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy for post concussion symptoms: issues may affect the results. Hu, Q., Manaenko, A., Guo, Z., et al.[2018]

Hyperbaric oxygen therapy (HBOT) has been shown to be an effective treatment for mild to moderate traumatic brain injury and persistent postconcussion syndrome, supported by B-level evidence from peer-reviewed clinical trials.

Current practices using pressurized air as a control in clinical trials may not be valid, as they can produce therapeutic effects similar to HBOT, thus potentially biasing the results of studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen: B-level evidence in mild traumatic brain injury clinical trials. Figueroa, XA., Wright, JK.[2017]

Hyperbaric oxygen therapy (HBOT) at 1.5 atmospheres absolute (ATA) has shown statistically significant improvements in symptoms and cognitive function for patients with Persistent Postconcussion Syndrome, based on a systematic review of 11 studies, including six randomized trials.

The review indicates that increased pressure is more crucial for therapeutic effects than increased oxygen levels, with the most effective results observed in patients receiving 40 treatments at 1.5 ATA, while varying outcomes were noted at different pressures and oxygen doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review and Dosage Analysis: Hyperbaric Oxygen Therapy Efficacy in Mild Traumatic Brain Injury Persistent Postconcussion Syndrome. Harch, PG.[2022]

A systematic review of 4 randomized controlled trials involving hyperbaric oxygenation (HBO) therapy found no significant improvement in post-concussion syndrome (PCS) symptoms compared to a sham treatment, indicating that HBO therapy may not be effective for this condition.

The analysis showed no meaningful differences in symptom scores on established questionnaires, suggesting that further large-scale clinical trials are needed to properly assess the efficacy of HBO therapy for PCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of hyperbaric oxygenation therapy on post-concussion syndrome. Dong, Y., Hu, X., Wu, T., et al.[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]

A study involving 61 male Marines with mild traumatic brain injury (mTBI) and postconcussion syndrome (PCS) found that hyperbaric oxygen (HBO2) treatment did not show significant improvement in symptoms or cognitive function by 3 months post-treatment.

The randomized, double-blind, sham-controlled design revealed no efficacy of HBO2 across various outcome measures, indicating that this treatment may not be effective for combat-related PCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen for blast-related postconcussion syndrome: three-month outcomes. Cifu, DX., Walker, WC., West, SL., et al.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3837504/

Hyperbaric Oxygen Therapy for Post-Concussion Syndrome The study demonstrated significant net improvements in PCS and PTSD symptoms with both doses of hyperbaric therapy.

2. 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12440767/

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.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2451865423001229

Hyperbaric Oxygen Therapy versus placebo for post- ... The HOT-POCS study will compare the efficacy of a standardized HBOT treatment protocol against a true placebo gas for the treatment of PCS within 12 months ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03339037

Hyperbaric Oxygen Therapy Effect on Post Concussion ... Relying on its results in adults, HBOT offers a promising new direction of treatment, which targets the basic pathological processes responsible for post- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00760734

Hyperbaric Oxygen Therapy (HBOT) in Chronic Traumatic ... This is a pilot trial to see if one or two 40 treatment courses of low pressure hyperbaric oxygen therapy can improve cognition and brain imaging in subjects ...

7. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/1935931

Effects of Hyperbaric Oxygen on Symptoms and Quality ... This multicenter, double-blind, sham-controlled clinical trial demonstrates that among service members with persistent postconcussion symptoms hyperbaric.