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Traumatic Brain InjuryPhase 3NCT06581003

Hyperbaric Oxygen Treatment for Veterans With Traumatic Brain Injury

A Phase 3 study testing Oxygen 99.7 % and Oxygen 21 % in people with Traumatic Brain Injury and Military Operations, run by University of South Florida at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Traumatic Brain Injury, Military Operations
What is being tested?
Oxygen 99.7 % and Oxygen 21 %
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
420 participants
Where
1 siteUnited States
Study dates
18 Sep 2024to 15 Aug 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • U.S. Service Members and Veterans, between 18 and 75 years of age
  • Ability to read, write, and speak English.
  • Ability to provide informed consent.
  • 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).
  • 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.
  • Able to tolerate the HBOT environment lying down for one hour.

Who cannot join

  • Received HBOT within the last 3 months.
  • Concurrently enrolled in another clinical trial.
  • Pregnancy or plans to become pregnant during the study period.
  • Lactating
  • History of retinal repair
  • Malignancy:
Show all 31Show fewer
  • Active
  • Tumor-related chemotherapy within the prior 6 months
  • Therapeutic radiation to the central nervous system within the prior year
  • 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?
  • Chronic use of supplemental oxygen or hypoxemia while breathing room air.
  • Untreated asthma/Bronchial obstruction/pulmonary blebs, recent/untreated pneumothorax
  • Congestive heart failure with ejection fraction < 40%
  • Any implanted devices not cleared for hyperbaric pressurization*.
  • Epilepsy and/ or seizures
  • Scuba diving within the previous month
  • Current suicidal intent as measured by ≥ 3 on the Columbia-Suicide Severity Rating Scale Screener
  • Trapped gas observed indicating Bronchospasm present Tension Pneumothorax
  • Evidence of Noncompliant TM (Until corrected)
  • Evidence of Pneumothorax
  • Evidence of Upper Respiratory Tract Infections
  • Signs and symptoms of viral infections, such as high fevers
  • Emphysema with CO2 retention
  • Optic Neuritis
  • Congenital spherocytosis
  • History of middle ear surgery / disorders
  • Pneumocephalus
  • Optional stool samples will not be collected if someone has diarrhea, vomiting, and took antibiotics in the past 30 days.
  • Antabuse because it predisposes to oxygen toxicity.
  • 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.
  • Inability to complete MRIs (e.g., claustrophobia, pacemaker, ferromagnetic implants)* Exclusion criteria for fMRI optional sub-study only

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Erik Velasquez contact

813-905-1043

erikv@usf.edu

Rachel A Karlnoski, PhD contact

7278584224

karlnosk@usf.edu

United States1 site, 1 recruiting
  • University of South Florida

    Tampa, Florida, 33612

    Harry Van Loveren, MD

    Shannon Miles, PhD

    Recruiting

Other trials in United States

About this study

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)
Read more

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
Read the detailed description

Participants who consent to the study will undergo a comprehensive baseline assessment in two sessions.

Baseline A. This visit will involve questions about the participant's brain injury and relevant medical history, and surveys to learn about symptoms related to the participant's mood, sleep, pain, behaviors (e.g. drug and alcohol use), and life satisfaction. Some surveys may be administered via an interview or as an electronic survey. After Baseline A assessments are completed, the investigators will determine if the participant meets the initial criteria to continue participation.

Baseline B. During this in-person visit, the investigators will have the participant do some thinking exercises by asking him/her to remember words, make decisions about shapes, draw and remember figures, and other similar tasks. The participant will also be asked questions about stress-related symptoms. The investigators will also draw up to 65-mL of blood from the participant's arm to detect inflammation and a brief physical exam (e.g. vision test, breathing functioning, heart rate). The participant will have a chance to complete optional procedure (described below). After Baseline B, the investigators will determine if the participant is eligible to continue their participation. If the participant is eligible, the next stage is "Randomization" to treatment. If the participant is not eligible, study participation will be over.

Randomization: The participant will be randomized to either HBOT (chamber pressurized to 2 ATA with 100% oxygen) or to a placebo condition (chamber that remains unpressurized and has 21% oxygen). The participant will not get to choose the treatment. The participant nor the PI will know which treatment is received.

HBOT or Placebo Dives: Both conditions will take place in a chamber, and each treatment session is called a "dive". The participant will then complete 40 HBOT or placebo dives in 12 weeks at USF. Every dive, the investigators will record the participant's blood pressure, respiration (breathing) rate, and pulse. If the participant is diabetic, the investigators will also record their glucose levels. Then the participant will change into a medical gown and lay down in a clear chamber for their dive. The participant will be in the chamber for about 76 minutes (60 min treatment). Every 5 dives, the participant will complete self-report measures about how they are currently feeling and a barotrauma screening. Every 10 dives, participants will undergo another a brief physical exam, similar to Baseline B. While the FDA has approved HBOT for some conditions, it is considered an experimental therapy for TBI. The entire visit should last about 90 minutes from self-report measures to getting dressed. The participant's regular medical treatment will not change if they take part in the research.

Mid-treatment Assessments: After the 20th dive is complete, the investigators will ask the participant to complete a mid-treatment assessment visit. The investigators do this to monitor how the participant are feeling and thinking. During this visit the participant will complete many of the same self-report measures and interviews as they did during the baseline visits. The participant will also give up to 65-mL of blood at this mid-treatment visit.

Posttreatment Assessments: After the 40 dives are complete, the investigators will ask the participant to complete 1 post-treatment visit at approximately 2 weeks after the last dive. The investigators do this to continue monitoring how the participant is feeling and thinking. During this assessment the participant will complete many of the same self-report measures and interviews as he/she did during the baseline visits and the mid-treatment visit. In addition, the participant will answer a question about global impression of change. They will also be asked to which group they believe they were assigned to: Treatment or Sham. The participant will also give up to 65-mL of blood. After the participant completes the Posttreatments assessments, the investigators will tell him/her which treatment he/she was randomized to receive. If the participant was randomized to the Placebo treatment, he/she will be given the opportunity to receive the actual treatment.

Being tested
Oxygen 99.7 %, Oxygen 21 %
Keywords
hyperbaric chamber, neuromodulation
Medical subject headings
Brain Injuries, Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oxygen 99.7 %Drug

    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 %Drug

    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.

Study groups in NCT06581003
Study groupRoleWhat they receive
HBOT GroupExperimentalHBOT chamber pressurized to 2.0 ATA with 100% oxygen
Receives: Drug: Oxygen 99.7 %
Placebo/Sham GroupSham comparatorHBOT chamber that remains unpressurized and has 21% oxygen
Receives: Drug: Oxygen 21 %

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from Baseline in the Neurobehavioral Symptoms at 2 weeks Post Intervention

    Measured by the Neurobehavioral Symptom Inventory (NSI). The severity of each symptom on the NSI is measured using a 5-item scale (0-none to 4-very severe) that asks patients to indicate the extent to which each symptom has disturbed them in the previous 2 weeks. The NSI total score is the sum of severity ratings of the 22 symptoms. Cluster scores (domains: physical, cognitive, affective, and sensory) were derived.

    Measured: at 2 weeks post treatment

Secondary outcomes (1)
  1. Change from Baseline in post traumatic stress disorder symptoms at 2 weeks post intervention

    measured by the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM-5); PTSD Checklist-5 (PCL-5). The PTSD Checklist for DSM-5 (PCL-5) is a self-report measure used to assess the presence and severity of PTSD symptoms based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). A score between 0-80 Higher Scores: Indicate a worse outcome, as they suggest a greater severity of PTSD symptoms.

    Lower Scores: Indicate a better outcome, as they suggest fewer or less severe PTSD symptom

    Measured: at 2 weeks post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2024
  2. Study start18 Sep 2024
  3. Primary completion15 Aug 2028 (estimated)
  4. Study completion15 Aug 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Blinded Group Sequential Adaptive Randomized Controlled Trial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
420 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06581003
Sponsor's protocol ID
STUDY006819: HBOT for TBI
Status last verified
Jul 2026
First submitted
23 Aug 2024
Last updated
15 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ajayi OD, Gaskill Z, Kelly M, Logue CJ, Hendricksen SM. A comparison of two hyperbaric oxygen regimens: 2.0 ATA for 120 minutes to 2.4 ATA for 90 minutes in treating radiation-induced cystitis Are these regimens equivalent? Undersea Hyperb Med. 2020 Fourth Quarter;47(4):581-589. doi: 10.22462/10.12.2020.7.

    PubMed 33227834
  • Daly S, Thorpe M, Rockswold S, Hubbard M, Bergman T, Samadani U, Rockswold G. Hyperbaric Oxygen Therapy in the Treatment of Acute Severe Traumatic Brain Injury: A Systematic Review. J Neurotrauma. 2018 Feb 15;35(4):623-629. doi: 10.1089/neu.2017.5225. Epub 2018 Jan 22.

    PubMed 29132229
  • Loignon A, Ouellet MC, Belleville G. A Systematic Review and Meta-analysis on PTSD Following TBI Among Military/Veteran and Civilian Populations. J Head Trauma Rehabil. 2020 Jan/Feb;35(1):E21-E35. doi: 10.1097/HTR.0000000000000514.

    PubMed 31479073
  • Neumann D, Kumar A, Van Loveren H; USF HBOT for Veterans with TBI Collaborative Group. Efficacy of hyperbaric oxygen treatment in veterans and service members with traumatic brain injury-a study protocol for a blinded three-stage group sequential randomized controlled trial. Trials. 2026 Mar 25;27(1):352. doi: 10.1186/s13063-026-09645-z.

    PubMed 41882764
  • Walters KF, Templeton JM, van Loveren H, Yusuf FR, Schilaty ND. EEG as a diagnostic tool and therapeutic monitor in traumatic brain injury: a sub-study methodology from the hyperbaric oxygen treatment for veterans with traumatic brain injury randomized controlled trial. Trials. 2026 Feb 16;27(1):227. doi: 10.1186/s13063-026-09531-8.

    PubMed 41692764

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Oxygen 99.7 % and Oxygen 21 % in people with Traumatic Brain Injury and Military Operations, run by University of South Florida at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 15 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Erik Velasquez (813-905-1043, erikv@usf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from Baseline in the Neurobehavioral Symptoms at 2 weeks Post Intervention (time frame: at 2 weeks post treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06581003, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2026.

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