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

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of hyperbaric oxygen therapy (breathing pure oxygen in a pressurized room) for individuals with persistent symptoms following a concussion. The goal is to reduce symptoms, enhance brain function, and improve overall quality of life compared to a placebo treatment that mimics the experience. It suits those experiencing moderate to severe symptoms for at least three months after a doctor has diagnosed a concussion. As an unphased trial, this study provides a unique opportunity to contribute to understanding and potentially improving treatment for concussion-related symptoms.

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 prior data suggests that hyperbaric oxygen treatment is safe for post-concussion syndrome?

Research shows that hyperbaric oxygen treatment (HBOT) is generally safe for people. Studies have found that HBOT can improve thinking skills in adults with post-concussion syndrome, indicating its safety for humans.

Previous research has not linked HBOT to major safety problems. Some individuals might experience mild discomfort, such as changes in ear pressure, but these are usually not serious. The FDA has already approved HBOT for other conditions, supporting its safety.

For those considering joining a trial, the safety information is encouraging. Always consult your healthcare provider to determine if this is a suitable option. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about hyperbaric oxygen therapy (HBOT) for post-concussion syndrome because it offers a unique approach compared to traditional treatments like rest, cognitive therapy, and medications for symptom management. Unlike these standard options, HBOT involves breathing 100% oxygen in a pressurized chamber, which increases oxygen delivery to the brain and may promote healing at a cellular level. This method has the potential to accelerate recovery by enhancing brain function and reducing inflammation, offering hope for quicker and more effective relief from persistent concussion symptoms.

What evidence suggests that Hyperbaric Oxygen Treatment might be an effective treatment for post-concussion syndrome?

Research has shown that Hyperbaric Oxygen Therapy (HBOT), which participants in this trial may receive, can help treat post-concussion syndrome (PCS). In one study, HBOT reduced symptoms like headaches and dizziness in people with mild traumatic brain injuries (mTBI). Another study found that HBOT significantly improved cognitive skills, making it easier for patients to think clearly. It also enhanced quality of life by alleviating ongoing symptoms. These findings suggest that breathing pure oxygen in a pressurized room can aid brain recovery after a concussion. ^{1 2 4 6 7}

Who Is on the Research Team?

James Berry, M.D.

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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) 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]

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 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]

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 Both doses were efficacious in the treatment of mTBI PCS and PTSD. The PTSD data demonstrated 18% and 22% reductions in the PCL-M (interpolated from the Figure ...

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. 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 ...

4. 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.

5. 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 ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11807354/

Evaluating the Impact of Hyperbaric Oxygen Therapy and ... Harch conducted a systematic review and dosage analysis with HBOT efficacy in mild traumatic brain injury persistent post-concussion syndrome.