Recruiting
Phase 3

Hyperbaric Oxygen

Sponsor:

University of South Florida

Code:

NCT06581003

Conditions

Traumatic Brain Injury

Military Operations

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Oxygen 99.7 %

Oxygen 21 %

Study Details

Brief summary:

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

Conditions

Traumatic Brain Injury

Military Operations

Study ID

NCT06581003

Start date

Sep 18, 2024

Status verified date

Jul, 2026

Completion date

Aug 15, 2029

Anticipated

Primary completion date

Aug 15, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

420 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: HBOT Group

HBOT chamber pressurized to 2.0 ATA with 100% oxygen

sham comparator: Placebo/Sham Group

HBOT chamber that remains unpressurized and has 21% oxygen

Interventions

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.

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.

Primary outcome measure

  • Change from Baseline in the Neurobehavioral Symptoms at 2 weeks Post Intervention [ Time Frame: at 2 weeks post treatment ]

Central Contacts and Locations

Central contacts

Rachel A Karlnoski, PhD

7278584224karlnosk@usf.edu

Locations

University of South Florida

Recruiting

Tampa, Florida, United States, 33612

Principal Investigator:

Harry Van Loveren, MD

More Information

Sponsor

University of South Florida

Last update posted

Jul 15, 2026

Last verified

Jul, 2026

Keywords

  • hyperbaric chamber
  • neuromodulation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of South Florida on 2026-07-15.