RECRUITINGPhase 3INTERVENTIONAL

Hyperbaric Oxygen Treatment for Veterans With Traumatic Brain Injury

About This Trial

The goal of this blinded, adaptive, randomized, placebo-controlled clinical trial is to investigate the use of hyperbaric oxygen as a therapy to treat mild to moderate traumatic brain injury in Veterans and active military. The main questions it aims to answer are: * Does Hyperbaric Oxygen Therapy (HBOT) reduce neurobehavioral symptoms? (Aim 1) * How many HBOT sessions are needed to achieve a significant reduction in neurobehavioral symptoms? (Aim 2) * Does HBOT reduce posttraumatic stress disorder (PTSD) symptoms? (Aim 3) Exploratory objectives will explore if there are changes in: 1.) cognitive functioning using neuropsychological tests and the National Institutes of Health (NIH) toolbox, 2.) inflammation biomarkers in blood, 3.) microbiome in stool samples, 4.) electroencephalogram (EEG), 5.) sleep characteristics, and 6.) fMRI. Research will compare HBOT therapy to a placebo condition to see if HBOT works to treat neurobehavioral symptoms. The placebo condition is a chamber that remains unpressurized and has 21% oxygen. Participants will: 1. Complete baseline assessments to determine eligibility. 2. Attend 40 sessions of HBOT or placebo (normal air) within 12 weeks. 3. Complete questionnaires and interviews throughout the course of the study. 4. Complete a 2-week post treatment visit

Who May Be Eligible (Plain English)

Who May Qualify: 1. U.S. Service Members and Veterans, between 18 and 75 years of age 2. Ability to read, write, and speak English. 3. Ability to provide willing to sign a consent form. 4. History of TBI. Participants must have a minimum of 1 year post injury and a TBI classified as mild to moderate as determined by with the Ohio State University TBI Identification Method (Bogner, 2009). 5. Experiencing chronic symptoms of TBI as determined by at least a NSI total score of ≥22 (based on previous work using this score; Harch et al., 2020. 6. Able to tolerate the HBOT environment lying down for one hour. Who Should NOT Join This Trial: 1. Received HBOT within the last 3 months. 2. Concurrently enrolled in another clinical trial. 3. Pregnancy or plans to become pregnant during the study period. 4. Lactating 5. History of retinal repair 6. Malignancy: 1. Active 2. Tumor-related chemotherapy within the prior 6 months 3. Therapeutic radiation to the central nervous system within the prior year 7. Current diagnosis of bipolar disorder type I or schizophrenia as determined by responses to inquiry: Have you ever been diagnosed or prescribed medications for bipolar disorder or schizophrenia? 8. Chronic use of supplemental oxygen or hypoxemia while breathing room air. 9. Untreated asthma/Bronchial obstruction/pulmonary blebs, recent/untreated pneumothorax 10. Congestive heart failure with ejection fraction \< 40% 11. Any implanted devices not cleared for hyperbaric pressurization\*. 12. Epilepsy and/ or seizures 13. Scuba diving within the previous month 14. Current suicidal intent as measured by ≥ 3 on the Columbia-Suicide Severity Rating Scale Screener 15. Trapped gas observed indicating Bronchospasm present Tension Pneumothorax 16. Evidence of Noncompliant TM (Until corrected) 17. Evidence of Pneumothorax 18. Evidence of Upper Respiratory Tract Infections 19. Signs and symptoms of viral infections, such as high fevers 20. Emphysema with CO2 retention ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. U.S. Service Members and Veterans, between 18 and 75 years of age 2. Ability to read, write, and speak English. 3. Ability to provide informed consent. 4. History of TBI. Participants must have a minimum of 1 year post injury and a TBI classified as mild to moderate as determined by with the Ohio State University TBI Identification Method (Bogner, 2009). 5. Experiencing chronic symptoms of TBI as determined by at least a NSI total score of ≥22 (based on previous work using this score; Harch et al., 2020. 6. Able to tolerate the HBOT environment lying down for one hour. Exclusion Criteria: 1. Received HBOT within the last 3 months. 2. Concurrently enrolled in another clinical trial. 3. Pregnancy or plans to become pregnant during the study period. 4. Lactating 5. History of retinal repair 6. Malignancy: 1. Active 2. Tumor-related chemotherapy within the prior 6 months 3. Therapeutic radiation to the central nervous system within the prior year 7. Current diagnosis of bipolar disorder type I or schizophrenia as determined by responses to inquiry: Have you ever been diagnosed or prescribed medications for bipolar disorder or schizophrenia? 8. Chronic use of supplemental oxygen or hypoxemia while breathing room air. 9. Untreated asthma/Bronchial obstruction/pulmonary blebs, recent/untreated pneumothorax 10. Congestive heart failure with ejection fraction \< 40% 11. Any implanted devices not cleared for hyperbaric pressurization\*. 12. Epilepsy and/ or seizures 13. Scuba diving within the previous month 14. Current suicidal intent as measured by ≥ 3 on the Columbia-Suicide Severity Rating Scale Screener 15. Trapped gas observed indicating Bronchospasm present Tension Pneumothorax 16. Evidence of Noncompliant TM (Until corrected) 17. Evidence of Pneumothorax 18. Evidence of Upper Respiratory Tract Infections 19. Signs and symptoms of viral infections, such as high fevers 20. Emphysema with CO2 retention 21. Optic Neuritis 22. Congenital spherocytosis 23. History of middle ear surgery / disorders 24. Pneumocephalus 25. Optional stool samples will not be collected if someone has diarrhea, vomiting, and took antibiotics in the past 30 days. 26. Antabuse because it predisposes to oxygen toxicity. 27. Other medications that would predispose to oxygen toxicity or known to increase drug toxicity will also be excluded. These are: Disulfuram, Acetazolamide, Sulfamylon; bleomycin, cisplatin, and doxyrubicin. 28. Inability to complete MRIs (e.g., claustrophobia, pacemaker, ferromagnetic implants)\* Exclusion criteria for fMRI optional sub-study only

Treatments Being Tested

DRUG

Oxygen 99.7 %

The experimental group will undergo HBOT in a specialized chamber at a pressure of 2.0 ATA. Oxygen will be delivered at 100% for 60 minutes.

DRUG

Oxygen 21 %

The control group will be placed in the same specialized chamber, but pressure will be 1.0 ATA (normobaric), and oxygen will be delivered at 21% (normal oxygen concentration in room air) for 60 minutes.

Locations (1)

University of South Florida

Tampa, Florida, United States