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
Study type: Interventional
Phase: Phase 2

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
    

Detailed description: 
      Brain injury due to trauma is very common; nonetheless, no pharmacological therapy is known
      to improve outcomes. Medications are used to treat symptoms, such as seizures and affective
      disorders, but are not intended to affect the fundamental problem. If HBO2, which is
      regularly available and relatively safe, improves outcome in brain-injured subjects by
      treating the underlying pathophysiology of post-concussive syndrome, this would represent a
      significant advance in treatment of brain injury. Hyperbaric oxygen (HBO2) has been proposed
      as a treatment for patients with TBI.

      Hyperbaric oxygen is one of the first pharmacologic interventions being tested in this
      population of individuals with mild TBI and chronic post-concussive symptoms targeted to
      improve cognition, memory, and functional status. However, much is unknown about how to
      measure improvement in post-concussive symptoms after an intervention in the targeted active
      duty population. In preparation for a pivotal efficacy study, the objectives of this study
      are to characterize two candidate primary outcome tools in our intended study population, the
      RPQ and the NSI, in order to better estimate the sample size needed to answer the efficacy
      question.

      Agency for Healthcare Research and Quality (AHRQ) conducted a comprehensive review of the
      literature, interviewed subject matter experts (SME), and conducted focus groups with SMEs to
      evaluate the evidence for HBO2 for patients with TBI. The AHRQ concluded that "Although they
      are cited frequently, the case series and time-series studies of HBO2 for TBI patients had
      serious flaws. There were no high-quality studies of the use of HBO2 to improve function and
      quality of life in patients with chronic, stable disabilities from TBI. The most important
      gap in the evidence is a lack of a good quality time-series study or controlled trial of the
      effects of HBO2 on cognition, memory, and functional status in patients with deficits due to
      mild chronic TBI." Similarly, the Department of Health and Human Services (DHHS) has not
      approved HBO2 therapy for the treatment of TBI as a covered condition, citing the lack of
      supporting evidence for clinical efficacy.

      The Defense Centers of Excellence for Psychological Health and Traumatic concluded that
      sufficient case reports, early safety and feasibility study data, and basic scientific
      plausibility exist to warrant prompt experimental study of HBO2 in the care of the full
      spectrum of chronic TBI. This would best be accomplished in a randomized, double-blind,
      multi-center clinical trial.

      This Phase 2 study, through specific study design, inclusion and exclusion criteria, interim
      and end point analyses, treatment protocols, dose-response and safety issues, evaluation
      methodologies, safety, and outcome measures address the need for clinical efficacy.

      In preparation for the pivotal trial, the purpose of this Phase II study is to describe the
      magnitude of change between baseline and follow-up outcomes for a battery of
      neuropsychological tests within groups. A secondary objective is to explore changes across
      the four groups. Differences and variability of the tests will be used for determining the
      optimum primary endpoint(s) for the Phase III trial, as well as for refinement of sample size
      and power calculations for this future study. Recruitment, randomization, blinding, and study
      and intervention logistics and planning will also be assessed.
    

Intervention name(s): hyperbaric oxygen; sham hyperbaric air
Intervention type(s): Drug; Other
Intervention description(s): 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.
Other intervention name(s): medical oxygen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: mild tramatic brain injury; mTBI; hyperbaric oxygen; post concussive symptoms; active duty military; veterans