Hyperbaric Oxygen Therapy (HBO2) for Persistent Post-concussive Symptoms After Mild Traumatic Brain Injury (mTBI)
Condition: Post-concussive Symptoms; Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Post-Concussion Syndrome; Wounds and Injuries
Intervention: hyperbaric oxygen; sham hyperbaric air
Intervention description: The chamber will be compressed with air to 1.5 atm abs. Once the chamber is compressed to 1.5 atm abs, the subjects will don a hood and breathe 100% oxygen. Hoods will be supplied with oxygen with flows of at least 30 liters per minute and overboard dumping of excess gas. Each subject will complete 40 sessions.
The duration of the hyperbaric oxygen exposures will be 60 minutes (±2 minutes), timed from when the chamber hatch or door closes, and ending when the chamber hatch or door opens ("door-to-door" time equals 60 minutes). The total intervention exposure time is 50 minutes (±2 minutes). The interval to compress to the intervention pressure (1.5 atm abs) and will be 5 minutes (±1 minute). The interval to decompress from the study pressure will be 5 minutes (±1 minute).; A pressure of 1.2 atm abs will provide an equivalent inhaled oxygen concentration of 25%. The duration of the sham exposures will be 60 minutes (±2 minutes). Each subject will complete 40 sessions.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 79.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: mild tramatic brain injury; mTBI; hyperbaric oxygen; post concussive symptoms; active duty military; veterans

Summary:

      This is a Phase II randomized trial designed to describe the magnitude of change between
      baseline and follow-up outcomes for symptom surveys and a battery of neuropsychological tests
      administered at time points corresponding before and after 10 weeks over observation in four
      groups:

        -  A military population with post-concussion syndrome (mTBI) receiving local standard care

        -  A military population with post-concussion syndrome (mTBI) receiving local standard care
           and sham hyperbaric oxygen sessions

        -  A military population with post-concussion syndrome (mTBI) receiving local standard care
           and hyperbaric oxygen at 1.5 atmospheres sessions

        -  A otherwise similar group with PTSD but no history of TBI receiving local standard care
           Differences and variability of the tests will be used for determining the optimum
           primary endpoint(s) for future trial, as well as for refinement of sample size and power
           calculations for these studies. The groups undergoing hyperbaric sessions will be
           assigned to receive HBO2 or sham using a randomized, double blind design.

      Active duty military (Army, Marine, Navy, Air Force) men and non-pregnant women residing in
      the United States and who will remain in the military for the entire study period, aged 18-65
      years who have been deployed one or more times to the US Central Command since the initiation
      of Operation Enduring Freedom (October 7, 2001) who either:

        -  have been diagnosed with Post Traumatic Stress Disorder (PTSD) as a result of traumatic
           events that occurred during the qualifying CENTCOM deployment, but have no diagnosed or
           suspected lifetime brain injuries resulting in loss or alteration of consciousness; OR

        -  have been diagnosed with at least one mild brain injury (mTBI) with persistent (> 4
           months) symptoms sustained during one or more of those deployments
    

Eligibility criteria:

        Inclusion Criteria:

          -  Volunteers must have history of at least one mild traumatic brain injury (mTBI) with
             persistent symptoms that meets all the following criteria:

               -  Brain injury that occurred more than 4 months prior to enrollment, with the most
                  recent injury occurring no earlier than October 7, 2001.

               -  Most recent traumatic brain injury occurred while serving on active duty, and
                  while deployed to the United States (US) Central Command (USCENTCOM).

               -  Most recent traumatic brain injury was caused by blast exposure or blunt trauma.

               -  Most recent traumatic brain injury resulted in at least one of the following: a
                  period of loss of or a decreased level of consciousness (up to 30 minutes); a
                  loss of memory for events immediately before or after the injury (up to 24
                  hours); or alteration in mental state at the time of the injury (becoming dazed
                  or confused).

          -  Volunteers must also meet all the following criteria:

               -  18-65 years old at the time of study enrollment.

               -  A TRICARE beneficiary at the time of consent and during study participation.

               -  Has current complaints of brain injury symptoms such as headache, dizziness, or
                  cognitive or affective problems that score at least 3 post-concussive symptoms as
                  assessed by the Ohio State University (OSU) Traumatic Brain Injury (TBI)
                  Identification (ID) Method interview

               -  Has received current local care pharmacologic and non-pharmacologic interventions
                  for TBI and any concomitant posttraumatic stress disorder (PTSD) with no
                  significant change in therapy for at least 1 month

               -  Willing and committed to comply with the research protocol and complete all
                  outcome measures.

               -  Able to self-consent.

               -  Able to speak and read English, as primary language.

               -  Able to participate in all outcome measures.

               -  Able to equalize middle ear pressure.

        Exclusion Criteria:

          -  History of brain injury of moderate or severe degree: duration of loss of
             consciousness at the time of injury greater than 30 minutes, or duration of
             post-traumatic amnesia greater than 24 hours, or brain injury of a penetrating
             etiology.

          -  History of brain injury not of traumatic etiology, such as stroke or drug-induced
             coma.

          -  Prior treatment with HBO2.

          -  Hyperbaric chamber inside attendant, professional (paid)underwater diver (commercial,
             operational/ military, instructor), or technical diver.

          -  Pregnancy, women who plan to become pregnant during the study period, women who do not
             agree to practice an acceptable form of birth control during the study period, or
             women who are breastfeeding;

          -  Those who are unable to participate fully in outcome assessments (Blind in one or both
             eyes; Deaf in one or both ears; or Ambulation with assistive devices

          -  Pre-existing diagnosis of a psychotic disorder(s): schizophrenia, dissociative
             disorder, and bipolar disease.

          -  Verifiable degenerative mental disease (e.g., Alzheimer's disease, multiple sclerosis,
             senile dementia).

          -  Epilepsy or seizure disorder requiring anticonvulsants.

          -  Active malignancy, prior malignancy (except basal cell carcinoma) within the last 5
             years.

          -  Presence of chronic debilitating disease (e.g., end-stage renal disease, end-stage
             liver disease, all types of diabetes with or without sequelae).

          -  Documented clinically significant uncorrected anemia

          -  Documented sickle cell disease.

          -  History of therapeutic ionizing radiation to the head.

          -  Verifiable diagnosis of learning disability.

          -  Positive urine test for an illicit substance(s).

          -  Any condition or use of prescribed medication (lithium, cisplatin, doxorubicin, or
             bleomycin) in which receipt of HBO2 would impact the safety of the individual.

          -  Anticipated administrative separation, prolonged temporary assigned duty (TAD/TDY) or
             deployment within 3 months after randomization

          -  Claustrophobia (unwilling or unable to enter hyperbaric chamber).

          -  Inability to protect airway or requires frequent suctioning; presence of tracheostomy

          -  Heart failure with ejection fraction < 50% (due to increased risk for precipitating
             acute lung edema during exposure to HBO2).

          -  Emphysema, chronic bronchitis, or bullous lung disease (due to risk for pulmonary
             barotrauma during hyperbaric decompression).

          -  Diabetes (relative contraindication related to risk of hypoglycemia).

          -  Presence of implanted device (e.g., cardiac defibrillator, intrathecal drug delivery
             device, cochlear implant) that poses increased risk to subject during hyperbaric
             exposure.