Hyperbaric Oxygen Therapy for Veterans With TBI and PCS: A Biomarker Study

Inclusion Criteria:

1. At least 18 years of age.
2. Veteran status
3. Clinically diagnosed with a TBI by a qualified healthcare professional.
4. Participants with comorbid post-traumatic stress disorder (PTSD), diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria by a qualified and trained professional, are eligible for enrollment but are not required for study participation.

4\. The participant is willing and able to read, understand, and sign an informed consent. Additionally, the participant has clear consciousness and the ability to express self-feelings independently.

6\. Completed psychological measurements (pre-study screening requirement) 7. Presence of clinically significant cognitive and/or PCS symptoms resulting in impairment in occupational, social, and other important areas of functioning, as determined by clinical evaluation.

8\. Sexually active female participants of childbearing potential and sexually active male participants with female partners of childbearing potential must agree to use an acceptable method of contraception for the duration of the study and for 30 days following the final HBOT session.

9\. Stability on any prescribed psychoactive medications and/or other chronic medical medications. Stability is defined as no significant changes in type of dosage within the previous 4-5 weeks, to minimize confounding effects on study outcomes and ensure participant safety.

Exclusion Criteria:

1. Untreated pneumothorax
2. History of spontaneous pneumothorax
3. Asymptomatic pulmonary lesions on chest x-ray
4. Uncontrollable high fever (greater than 39C)
5. History of chest or ear surgery
6. Congenital spherocytosis
7. Any anemia or blood disorder
8. Any convulsive disorder
9. History of optic neuritis or sudden blindness
10. Middle ear infection
11. Diabetes mellitus (insulin therapy)
12. The participant is pregnant or lactating
13. Nicotine use/substance use/addiction
14. Acute Hypoglycemia
15. Diagnosed Chronic Obstructive Pulmonary Disease (COPD) and Emphysema
16. Presenting with symptoms of cough, congestion, vomiting, diarrhea, or open wounds.
17. Active malignancy
18. Current manic, delusional, or psychotic episodes
19. Serious/current suicidal ideations
20. Severe or unstable physical disorders or major cognitive deficits
21. Inability to attend scheduled clinic visits or comply with study protocols.
22. Treated with HBOT for any reason prior to study enrollment.
23. Non-English speakers
24. History of retinal repair, including laser photocoagulation or retinal detachment surgery.
25. History of middle ear surgery, including tympanoplasty, mastoidectomy, or pressure equalization tube placement.
26. Age greater than 75 years.
27. Use of any of the following medications during the study period: Anti-metabolites (e.g., methotrexate, azathioprine); Chemotherapeutic agents (e.g., cyclophosphamide, cisplatin); Mafenide acetate e.g., Sulfamylon); Disulfiram (e.g, Antabuse); Peripheral vasodilators known to interact with oxygen exposure (e.g., nitroglycerin); and Antibacterial drugs with known HBOT interaction risks.
28. Recent vaccination (≤ 1 week), or underlying inflammatory conditions
29. Use of systemic corticosteroids or immunomodulatory therapies
30. Active or recent infection requiring antibiotics.
31. Significant renal or hepatic impairment.
32. Regular participation in intense physical training or exercise programs (Defined as endurance events (e.g., triathlons, marathons, ultramarathons, Ironman-level training) or high-intensity interval training (HIIT) programs performed multiple times per week)
33. Recent (within 4 weeks prior to baseline) or planned use of antioxidant supplements or high-dose vitamins (Examples include: Vitamin C (\> 500 mg/day), Vitamin E (\>200 IU/day), N-acetylcysteine (NAC) or other thiol-based antioxidants, Alpha-lipoic acid, high-dose multivitamins containing the above doses, or Omega-3 fatty acid concentrates taken specifically for antioxidant/anti-inflammatory purposes)
34. Recent participation in other clinical trials that could affect biomarker levels.
35. Untreated or severe sleep disorders