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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment of U.S. Veterans with mild traumatic brain injury with hyperbaric oxygen therapy | Other | Pilot 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxygen 100 % Gas for Inhalation | Drug | Oxygen 100% Gas for Inhalation in Hyperbaric Oxygen Therapy Chamber at 1.5 ATA |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | pre- HBOT and 4 weeks after HBOT |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
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Inclusion Criteria:
A male U.S. Veteran, suffer from mild traumatic brain injury characterized by:
Exclusion Criteria:
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
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.
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| Name | Affiliation | Role |
|---|---|---|
| Alison C Bested, MD FRCPC | Nova Southeastern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nova Southeastern University | Fort Lauderdale | Florida | 33328 | United States |
Will need time from data support person to help with data sharing.
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| ID | Term |
|---|---|
| D001924 | Brain Concussion |
| D003863 | Depression |
| D013405 | Suicide |
| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D010100 | Oxygen |
| D005740 | Gases |
| D001239 | Inhalation |
| ID | Term |
|---|---|
| D018011 | Chalcogens |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D015656 | Respiratory Mechanics |
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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.
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|
| Hyperbaric Oxygen Therapy Chamber | Device | Hyperbaric Oxygen Therapy, 40 treatments, at 1.5 ATA and 100% Oxygen |
|
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| Traumatic Brain Injury Screening Tool | Criteria for Mild Traumatic Brain Injury:
| pre- HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1 month after HBOT |
| 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. | pre- HBOT and 1 month after HBOT |
| 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. | pre- HBOT and 1 month after HBOT |
| 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. | pre- HBOT and 1 month after HBOT |
| 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. | pre- HBOT and 1 month after HBOT |
| 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. | pre- HBOT and 1 month after HBOT |
| 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. . | pre- HBOT and 1 month after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| 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. | pre- HBOT and 1, 6. 12 months after HBOT |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D016489 | Head Injuries, Closed |
| D014947 | Wounds and Injuries |
| D014949 | Wounds, Nonpenetrating |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D016728 | Self-Injurious Behavior |
| D012119 |
| Respiration |
| D012143 | Respiratory Physiological Phenomena |
| D002943 | Circulatory and Respiratory Physiological Phenomena |