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Mild Traumatic Brain InjuryPhase 1NCT06665633

Treatment of U.S. Veterans With Mild Traumatic Brain Injury With Hyperbaric Oxygen Therapy

A Phase 1 study testing Oxygen 100 % Gas for Inhalation and Hyperbaric Oxygen Therapy Chamber in people with Mild Traumatic Brain Injury and Hyperbaric Oxygen Therapy, run by Nova Southeastern University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Mild traumatic brain (mTBI) injury affects 400,000 U.S. Veterans resulting in physical, cognitive and mental health symptoms. The Department of Defense (DoD) reported 26 suicides a day from mTBI despite ongoing care for the Veterans. Read more about this study

Who is it for?
Ages 18 to 70 years, men only
What is being tested?
Oxygen 100 % Gas for Inhalation and Hyperbaric Oxygen Therapy Chamber
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
7 Sep 2021to 1 Jul 2025
Phase
Phase 1
Are there results?
None posted in the registry

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 70 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A male U.S. Veteran, suffer from mild traumatic brain injury characterized by:
  • a confused or disoriented state which lasts less than 24 hours
  • loss of consciousness for up to 30 minutes
  • memory loss lasting less than 24 hours. In good health prior to mild traumatic brain injury.

Who cannot join

  • An individual is ineligible to participate if does not meet the criteria for mild traumatic brain injury and if any of the following apply:
  • Female gender due to small pilot study and hormonal changes in women.
  • Current treated or untreated major depression with psychotic or melancholic features, schizophrenia, bipolar disorder, delusional disorders, dementias of any type, and alcoholism or drug abuse
  • Current heavy use of alcohol or tobacco use (self-report in last 6 months)
  • Current organ failure (as determined by self-report)
  • Current treated or untreated rheumatologic and inflammatory disorders, as determined by medical diagnosis of one or more of the following: osteoarthritis, rheumatoid arthritis, lupus erythematosus, spondyloarthropathies - ankylosing spondylitis and psoriatic arthritis, Sjogren's syndrome, gout, scleroderma, infectious arthritis, and polymyalgia rheumatica
Show all 22Show fewer
  • Chronic active infections such as HIV, hepatitis B, and hepatitis C (self-report)
  • History of organ transplant (self-report)
  • Current primary sleep disorders such as insomnia, sleep related breathing disorders, etc.
  • (self-report)
  • Any allergic disease (self-report) such as allergic asthma
  • Use of medications that could affect immune function (e.g., steroids, immunosuppressants) (self-report)
  • Renal insufficiency
  • Hepatic insufficiency
  • Currently have no exclusionary diagnoses that could reasonably explain the symptoms of their fatiguing illness and their severity, using the exclusion criteria best described in case definition paper for Chronic Fatigue Syndrome (CFS), as described in detail in Reeves, et all 2003, which clarifies exclusionary conditions.
  • History of moderate to severe traumatic brain injury or TBI requiring hospitalization in the past five years.
  • Unstable PTSD or PTSD requiring hospitalization in the past 5 years (stable PTSD is allowed) - this is to reduce the risk of a claustrophobic triggering of PTSD symptoms.
  • (limits generalizability of results to mild/moderate stable PTSD)
  • Are scheduled for surgery during time of hyperbaric oxygen treatments.
  • Contraindication for HBOT Therapy: untreated collapsed lung.
  • Relative contraindications for HBOT Therapy: Includes pulmonary diseases including chronic obstructive lung disease, an air blister in the lung that appears on a chest radiograph but does not result in symptoms, upper respiratory or sinus infections, recent ear or thoracic surgery, uncontrolled fever, and claustrophobia. However, these are relative contraindications, which should not deter clinicians from using HBOT to treat patients with severe neurological injuries or other life or limb threatening conditions. The adverse effects of several medications are thought to be increased by HBOT, including bleomycin and doxorubicin. Other exclusions from participation includes pregnancy and participating in another interventional clinical trial of an investigational therapy within 30 days of consent or scheduled for surgery.
  • Contraindication for brain SPECT scan: Known allergy to radioactive tracer material.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Nova Southeastern University

    Fort Lauderdale, Florida, 33328

Other trials in United States

About this study

Mild traumatic brain (mTBI) injury affects 400,000 U.S. Veterans resulting in physical, cognitive and mental health symptoms. The Department of Defense (DoD) reported 26 suicides a day from mTBI despite ongoing care for the Veterans. The purpose of this pilot research study is to evaluate the effect of treating Veterans suffering from mTBI or persistent post-concussion syndrome with hyperbaric oxygen therapy (HBOT).

Read the detailed description

In 40 male U.S. Veterans, who have had chronic mTBI for at least six months, the effect of HBOT will be measured in this pilot study with online questionnaires before and after HBOT to measure mental health issues (e.g. depression) and brain function (e.g. memory). The questionnaires will be repeated at 6 and 12 months after HBOT. Brain SPECT (single-photon emission computerized tomography) scans, will measure blood flow to the brain's injured areas before and after HBOT. Quantitative Electroencephalography (QEEG)) will measure brain electrical signals before and after HBOT. An overnight sleep study will measure the quality and stages of sleep pre- and post-HBOT. Blood tests will measure inflammation and cellular mitochondrial function (energy production by the cell) before and after HBOT.

Being tested
Oxygen 100 % Gas for Inhalation, Hyperbaric Oxygen Therapy Chamber
Keywords
Mild Traumatic Brain Injury, Hyperbaric Oxygen Therapy, Brain SPECT Scan, Brodmann Areas, Suicide, Depression
Medical subject headings
Brain Concussion, Depression, Suicide

What participants receive

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

  • Oxygen 100 % Gas for InhalationDrug

    Also called Oxygen

    Oxygen 100% Gas for Inhalation in Hyperbaric Oxygen Therapy Chamber at 1.5 ATA

  • Hyperbaric Oxygen Therapy ChamberDevice

    Hyperbaric Oxygen Therapy, 40 treatments, at 1.5 ATA and 100% Oxygen

Study groups in NCT06665633
Study groupRoleWhat they receive
Treatment of U.S. Veterans with mild traumatic brain injury with hyperbaric oxygen therapyOtherPilot Study - A total of 40 HBOT treatments at 1.5 atmospheres absolute (ATA) for a dive time of 60 minutes, twice a day Monday through Friday. The treatments were separated by an air break of 4 hours on the same day. Measurements of the effectiveness of HBOT in mTBI done before and after HBOT.
Receives: Drug: Oxygen 100 % Gas for Inhalation; Device: Hyperbaric Oxygen Therapy Chamber

What is being measured

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

  1. Brain SPECT Scan

    A brain SPECT scan is a type of imaging test that uses a radioactive substance and a special camera to create 3D pictures of the brain. It shows which areas of the brain are functioning the best or worst and how well the blood flows in the brain. The blood flow to the brain was measured pre- and post-HBOT. An infusion of a radioactive tracer, 30 millicurie (mCi) of Tc99m-Ceretec, was injected into the Veteran's IV site. The veteran was placed under the gamma scintillation camera (Siemens E-cam Dual Head) with a low-energy, high-resolution collimator and SPECT images were recorded using the NeuroGam Software Analysis for the numerical calculation of the mean blood flow value for each of the Brodmann Areas - which are the functional areas in the brain.

    Measured: pre- HBOT and 4 weeks after HBOT

Secondary outcomes (28)
  1. Beck Anxiety Inventory

    The Beck Anxiety Inventory (BAI) is a validated 21-item self-report questionnaire used to assess the severity of anxiety symptoms. Higher scores indicate more severe symptoms. A score of 0-7 indicates minimal anxiety, 8-15 mild anxiety, 16-25 moderate anxiety, and 26-63 severe anxiety.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  2. Beck Depression Inventory II

    The Beck Depression Inventory is a validated self-report questionnaire that indicates the severity of depressive symptoms. Scores are typically categorized as minimal (0-13), mild (14-19), moderate (20-28), or severe (29-63) depression, with higher scores indicating more pronounced symptoms.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  3. Brief Pain Inventory

    It is a validated self-report questionnaire used to assess pain in patients. It measures the intensity of pain (severity) and how it interferes with daily activities (interference). It is scored by calculating the mean of the items for pain severity and pain interference, each on a scale of 0-10. The higher the score, the more intense the pain and the more it interferes with daily activities.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  4. Traumatic Brain Injury Screening Tool

    Criteria for Mild Traumatic Brain Injury:

    • Confused/disoriented state that lasts less than 24 hours
    • Loss of consciousness for up to 30 minutes
    • Memory loss lasting less than 24 hours
    • Excluded severe TBI with skull penetrating injury, brain hemorrhage Other cognitive difficulties include feeling dazed, groping for words, and having problems with attention, concentration, processing speed, planning, reasoning, and abstract thinking. Physical symptoms include headache, nausea, vomiting, drowsiness, fatigue, dizziness, loss of balance, blurred vision, unrefreshed sleep, sensitivity to light or sound, tinnitus, and alteration of taste or smell. Some patients also experience mental health symptoms including anxiety, depression, post-traumatic stress disorder, and suicide ideation

    Measured: pre- HBOT

  5. Davidson Trauma Scale

    It is a validated 17-item self-report questionnaire used to assess the severity of post-traumatic stress disorder (PTSD) symptoms. The total score, which can range from 0 to 136. Higher scores indicate more severe PTSD symptoms.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  6. Functional Capacity Scale

    Self-report scale from 0 to 10 to measure the severity of fatigue and cognitive ability. Better energy and cognitive function is reflected in a higher number.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  7. Pittsburgh Sleep Quality Index

    It is a validated self-report questionnaire that assesses sleep quality over a one-month time interval. The sum of these component scores yields a global PSQI score, ranging from 0 to 21, with higher scores indicating poorer sleep quality. A global PSQI score greater than 5 is generally considered indicative of poor sleep quality.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  8. The Quick Environmental Exposure and Sensitivity Inventory (QEESI)

    It is a validated self-report questionnaire that helps researchers, doctors, and their patients identify individuals with multiple chemical intolerances and their responses to the chemicals. The score is 0-10 with the higher score indicating a worse response to chemical exposures.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  9. Short-Form 36 Health Survey

    It is a validated questionnaire used to measure health-related quality of life. It has eight scaled scores, each ranging from 0 to 100, with lower scores indicating more disability and higher scores indicating less disability. The eight scales are physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  10. Quantitative Electroencephalography

    It measures the electrical activity in the form of brain wave patterns of the brain. It is called brain mapping and measures quantitative metrics related to cognitive brain functions. It quantitatively measures the delta, theta, alpha and beta bands.

    Measured: pre- HBOT and 1 month after HBOT

  11. Overnight Sleep Study

    The Cerebra software system is used at home and measures the sleep for one night and includes measuring the percentage of oxygen saturation in the blood as % oxygen using a pulse oximeter, measures heart rate in beats per minute on ECG, breathing rate - measures breathes per minute, limb movement - records leg movement per hour, measures total minutes of time spent snoring, measures the sleep position - in minutes of time spent on back or sides, and measures amount of minutes on EEG brain waves in the different sleep stages including: non-rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, and stages III/IV sleep. A final report summarizes the sleep study findings.

    Measured: pre- HBOT and 1 month after HBOT

  12. Measure Blood Markers of Inflammation

    Measure 18 blood cytokines using Q-Plex Array. Measures levels of Tumor Necrosis Factor-1, Interleukin-1a,Interleukin-1b, Interleukin-2, Interleukin-4, Interleukin-5, Interleukin-6,Interleukin -8, Interferon gamma, Interleukin12p70, Interleukin-13, Interleukin-23, Interleukin-15, Interleukin-17, Interleukin-10, Tumor Necrosis Factor alpha, Tumor Necrosis Factor-Receptor II, Tumor Necrosis Factor beta. All cytokines were measured in picograms/milliliter and measured in the Multiplex Cytokine Analyzer. All of the individual cytokines were compared to normal, high, and low controls.

    Measured: pre- HBOT and 1 month after HBOT

  13. PTSD Checklist - Stressor Specific Version (PCL-S)

    The PCL is a validated 17-item self-report measure of the DSM-IV symptoms of PTSD. Respondents rate how much they were "bothered by a symptom" on a 5-point scale ranging from 1 ("not at all") to 5 ("extremely"). A higher score indicates the more severe outcome. A score between 31 and 33 is often used as a cut-off score to indicate probable PTSD with 80 the maximum score.

    Measured: pre- HBOT and 1 month after HBOT

  14. Clinical Criteria for Traumatic Brain Injury Severity

    Clinical Criteria: Mild, Moderate, Severe.

    Structural Imaging: Normal, Normal or abnormal, Normal or Abnormal.

    Loss of Consciousness: < 30 minutes, 30 minutes to 24 hours, > 24 hours.

    Alteration of Consciousness/Mental State: A moment to 24 hrs. > 24 hours > 24 hours.

    Post-traumatic Amnesia: 0-1 day, > 1 and < 7 days, > 7 days.

    Measured: pre- HBOT and 1 month after HBOT

  15. Mitochondrial Function

    Mitochondrial function is measured in the peripheral blood mononuclear cells (PBMCs) using the Seahorse™ Assay. The PBMCs reflect functioning of the brain's neurons and will assess if there is mitochondrial repair after hyperbaric oxygen therapy.

    Measured: pre- HBOT and 1 month after HBOT

  16. Measure DNA Repair

    DNA repair measured by measuring Nucleotide Excision Repair in peripheral blood mononuclear cells (PBMCs), which is a reflection of what is occurring in the brain's neurons and will assess if there is DNA repair after hyperbaric oxygen therapy. .

    Measured: pre- HBOT and 1 month after HBOT

  17. Neurocognitive Index

    It is the average of five domain scores: Composite Memory, Psychomotor Speed, Reaction Time, Complex Attention , and Cognitive Flexibility ; representing a form of a global score of neurocognition. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  18. Composite Memory

    Questionnaire measures the ability to recognize, remember, and retrieve words and geometric figures. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  19. Verbal Memory

    Questionnaire measures the ability to recognize, remember, and retrieve words. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  20. Visual Memory

    Questionnaire measures the recognition memory for abstract figures or shapes. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  21. Finger Tapping

    Online computer test process that measures motor speed and fine motor control. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  22. Symbol Digit Coding

    Online computer test process that measures complex information, processing accuracy, complex attention, visual-perceptual speed, and information processing speed. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  23. Stroop Test

    Online computer test process that measures simple reaction time, complex reaction time, Stroop reaction time, inhibition/disinhibition, and frontal or executive skills. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  24. Shifting Attention

    Online computer test process that measures the ability to shift from one instruction set to another quickly and accurately. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  25. Continuous Performance

    Online computer test process that measures vigilance or sustained attention or attention over time. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  26. Perception of Emotions

    Questionnaire measures how well a subject can perceive and identify specific emotions. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  27. Non-Verbal Reasoning

    Questionnaire measures how well a subject can perceive and understand the meaning of visual or abstract information and recognizing relationships between visual-abstract concepts. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

  28. 4-Part Continuous Performance

    It is a four-part online computer test that measures a subject's working memory and sustained attention. Scores range from less than 70, very low, to greater than 109, above average.

    Measured: pre- HBOT and 1, 6. 12 months after HBOT

Timeline

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

  1. First posted30 Oct 2024
  2. Study start7 Sep 2021
  3. Primary completion1 Jul 2025
  4. Study completion1 Jul 2025

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Pilot study - to study the effect of 40 treatments of hyperbaric oxygen therapy using 100% oxygen and increased atmospheric pressure of 1.5 atmospheres for 60 minutes on chronic mild traumatic brain injury with a wait time of at least 6 months or more after the traumatic brain injury occurred in the U.S. Veterans.
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06665633
Sponsor's protocol ID
IRB#: 2021-406
Status last verified
Aug 2025
First submitted
12 Jul 2024
Last updated
26 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
Undecided: Will need time from data support person to help with data sharing.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Oxygen 100 % Gas for Inhalation and Hyperbaric Oxygen Therapy Chamber in people with Mild Traumatic Brain Injury and Hyperbaric Oxygen Therapy, run by Nova Southeastern University 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 4 inclusion and 22 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: finished, as of the sponsor's last update on 26 Aug 2025. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brain SPECT Scan (time frame: pre- HBOT and 4 weeks after HBOT). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 26 Aug 2025.

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