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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Persistent post-concussive symptoms (PPCS) are a source of significant burden among a subset of patients with concussion with prevalence rates previously reported between 11 - 82% based on timing of assessment, diagnostic criteria, or population under study. Examples of persistent post-concussion symptoms include balance problems, headaches, fatigue, poor concentration, forgetfulness, anxiety, irritability, and sleep disturbance. Few proposed therapies have proved successful in the management of persistent post-concussion symptoms following mild traumatic brain injury. The investigators will explore hyperbaric oxygen administered in a randomized sham-controlled clinical trial as an effective and tolerable treatment in improving neuropsychological status among adult patients with persistent post-concussive symptoms. The overall hypothesis to be evaluated is that hyperbaric oxygen improves neuropsychological status and a serum concussion biomarker associated with PPCS.

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.

What data supports the effectiveness of Hyperbaric Oxygen Therapy for Post-Concussion Syndrome?

Research shows mixed results for Hyperbaric Oxygen Therapy (HBOT) in treating Post-Concussion Syndrome (PCS). Some studies suggest it may help with mild traumatic brain injuries, but others found no significant difference compared to placebo treatments, indicating more research is needed to confirm its effectiveness. ^{1 2 3 4 5}

Is hyperbaric oxygen therapy generally safe for humans?

Hyperbaric oxygen therapy (HBOT) is generally safe for humans, with rare occurrences of minor issues like ear or sinus discomfort and headaches. Serious adverse events are uncommon, and safety data from over 1.5 million treatments show that significant problems are rare. ^{6 7 8 9 10}

How does hyperbaric oxygen therapy differ from other treatments for post-concussion syndrome?

Hyperbaric oxygen therapy (HBOT) is unique because it involves breathing pure oxygen in a pressurized room, which increases the amount of oxygen in the blood and is thought to help heal damaged tissues. Unlike other treatments, HBOT combines increased barometric pressure with high oxygen levels, which is not typically used in standard therapies for post-concussion syndrome. ^{1 3 10 11 12}

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

Eligibility Criteria

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

I am 18 years old or older.

Willing and able to provide informed consent

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

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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) 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]

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]

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]

References

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

Hyperbaric oxygen: B-level evidence in mild traumatic brain injury clinical trials. [2017]

2. Greece pubmed.ncbi.nlm.nih.gov

Effect of hyperbaric oxygenation therapy on post-concussion syndrome. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. Netherlands pubmed.ncbi.nlm.nih.gov

Hyperbaric Oxygen Therapy versus placebo for post-concussion syndrome (HOT-POCS): A randomized, double-blinded controlled pilot study. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Sleep assessment in a randomized trial of hyperbaric oxygen in U.S. service members with post concussive mild traumatic brain injury compared to normal controls. [2019]

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

Adverse events and blinding in two randomized trials of hyperbaric oxygen for persistent post-concussive symptoms. [2019]

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

Clinical results in brain injury trials using HBO2 therapy: Another perspective. [2015]

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

Hyperbaric oxygen therapy for post concussion symptoms: issues may affect the results. [2018]

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

Hyperbaric oxygen for blast-related postconcussion syndrome: three-month outcomes. [2014]

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

The effect of hyperbaric oxygen on symptoms after mild traumatic brain injury. [2022]

12. United States 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. [2021]