Hyperbaric Oxygen Therapy for Post-Concussion Syndrome

Overseen By Brittany Wright, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Antabuse, Antiseizure, Meclizine, others

Disqualifiers: COPD, Uncontrolled HTN, Pregnancy, others

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

Compensation: Varies

Number of Visits: 21

Duration: 4 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to decrease symptom burden, improve cognitive function, and improve quality of life outcomes in subjects with mild TBI and persisting post-concussion syndrome using Hyperbaric Oxygen Treatment compared to a sham intervention. Specific Aims: 1. Evaluate the efficacy of hyperbaric oxygen treatment to improve outcomes for adults with persisting post-concussion syndrome. Specifically, the investigators hypothesize that a prescribed course of hyperbaric oxygen treatments (HBOT) will improve outcomes and quality of life in adults with persisting symptoms \>3 months after injury. 1. Decrease symptom burden as measured by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). 2. Improve cognitive function as measured by the National Institutes of Health (NIH) Toolbox Cognition Battery. 3. Improve quality of life as measured by the 36-Item Short Form Survey (SF-36). 2. Assess the safety and tolerability of hyperbaric oxygen treatments and compliance with treatment in adults with persisting post-concussion syndrome.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but certain medications may require approval from the hyperbaric medicine physician. If you are taking medications like antiseizure drugs, meclizine, or corticosteroids, you may need to have your medication levels checked or get approval before participating.

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

Some studies suggest that hyperbaric oxygen therapy (HBOT) may help with mild traumatic brain injury, but its effectiveness for post-concussion syndrome is still debated. While HBOT has shown promise in treating more severe brain injuries, more research is needed to confirm its benefits for post-concussion symptoms. ^{1 2 3 4 5}

Is hyperbaric oxygen therapy safe for humans?

Hyperbaric oxygen therapy is generally considered safe, but some side effects can occur, such as ear pain due to pressure changes, anxiety from being in a confined space, and in rare cases, seizures. These side effects have been observed in various studies involving many patients. ^{6 7 8 9 10}

How is hyperbaric oxygen therapy different 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 can help heal damaged tissues. Unlike other treatments, HBOT combines increased barometric pressure with high oxygen levels, which may offer benefits for post-concussion syndrome, although its effectiveness is still debated. ^{1 2 3 5 11}

Research Team

Shanti Pinto, MD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

This trial is for adults who were diagnosed with a concussion by a medical professional within 48 hours of injury and are still experiencing moderate to severe symptoms 3-12 months later. It's not suitable for individuals with significant heart, lung, neurological or psychiatric conditions, those with certain blood disorders, uncontrolled seizures, drug/alcohol abuse, claustrophobia or pregnant women.

Inclusion Criteria

Must have been evaluated within 48 hours of injury and given a diagnosis of concussion by a medical professional

I have had moderate to severe concussion symptoms for 3-12 months.

Exclusion Criteria

I have COPD with CO2 retention or lung issues like hyperinflation.

Miscellaneous: Current fever or active infection, Implanted devices not on the approved list for use with HBOT, Women who are pregnant. Women with childbearing potential are required to use effective birth control if not surgically sterile or postmenopausal for >2 years, Undergoing vestibular or other therapy during the intervention, Planning a change in medication during the intervention

I am currently on chemotherapy, or have a history of bleomycin use, Hereditary Spherocytosis, or Sickle cell anemia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hyperbaric oxygen treatment or placebo gas for 90-minute sessions, 5 days per week, for 20 sessions

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Hyperbaric Oxygen Treatment
• Placebo gas

Trial Overview The study tests if Hyperbaric Oxygen Treatment (HBOT) can reduce symptoms and improve cognitive function and quality of life in adults with post-concussion syndrome compared to a placebo gas treatment. Participants' symptom burden will be measured using the Rivermead Questionnaire; cognitive function via NIH Toolbox; and quality of life through SF-36 survey.

Participant Groups

Group I: HBOT Arm Experimental Treatment 1 Intervention

Pressurized at 2.0 atmospheres absolute of pressure (ATA) Breathe 100% oxygen 90 minute session, 5 days per week, for 20 sessions

Group II: Control Arm Placebo Group 1 Intervention

Placebo Gas Pressurized at 2.0 ATA Breathe placebo gas system of 10.5% oxygen and 89.5% nitrogen to mimic the partial pressure of oxygen breathed in regular air at sea level pressure 90 minute session, 5 days per week, for 20 sessions

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

Approved in United States as Hyperbaric Oxygen Therapy for:

• Carbon monoxide poisoning
• Decompression sickness
• Diabetic foot ulcers
• Wound healing

Approved in European Union as Hyperbaric Oxygen Therapy for:

• Carbon monoxide poisoning
• Decompression sickness
• Diabetic foot ulcers
• Wound healing
• Radiation necrosis

Approved in Canada as Hyperbaric Oxygen Therapy for:

• Carbon monoxide poisoning
• Decompression sickness
• Diabetic foot ulcers
• Wound healing

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

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 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]

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) 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) 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 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 five-year study of 2,610 patients undergoing hyperbaric oxygen therapy (HBO2), 10.04% experienced middle ear barotrauma (MEB), highlighting it as a common side effect that can lead to premature treatment discontinuation.

Risk factors for MEB included being over 55 years old, female gender, and having a history of ear, nose, and throat issues, suggesting that identifying and managing these factors could help reduce the incidence of this adverse event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Middle-ear barotrauma after hyperbaric oxygen therapy: a five-year retrospective analysis on 2,610 patients. Edinguele, WFOP., Barberon, B., Poussard, J., et al.[2021]

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]

In a study of 2,334 patients undergoing hyperbaric oxygen (HBO2) therapy, 17.4% experienced adverse events, with the most common being middle ear barotrauma affecting 9.2% of patients.

Despite some side effects, the overall incidence of complications was low at 0.72% per session, indicating that with proper protocols and monitoring, HBO2 therapy is a safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of hyperbaric oxygen treatment--retrospective analysis in 2,334 patients. hadanny, A., Meir, O., Bechor, Y., et al.[2016]

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. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

4. Greece pubmed.ncbi.nlm.nih.gov

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

5. Australia pubmed.ncbi.nlm.nih.gov

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

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

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

7. 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]

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

Middle-ear barotrauma after hyperbaric oxygen therapy: a five-year retrospective analysis on 2,610 patients. [2021]

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

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

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

The safety of hyperbaric oxygen treatment--retrospective analysis in 2,334 patients. [2016]

11. 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]