Hyperbaric Oxygen Therapy (HBO2)for Persistent Post-concussive Symptoms After Mild Traumatic Brain Injury (mTBI) (HOPPS)
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
Traumatic Brain Injury
Drug: hyperbaric oxygen
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Pilot Phase II Study of Hyperbaric Oxygen for Persistent Post-concussive Symptoms After Mild Traumatic Brain Injury (HOPPS)|
- Rivermead Post-Concussion Symptom Questionnaire to measure change from baseline [ Time Frame: Change from Baseline of RPQ/RPQ-3 at time of randomization to Day 28 and Day56 ] [ Designated as safety issue: No ]The Rivermead Post-Concussion Symptom Questionnaire (RPQ)/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. The scale compares any current symptoms to pre-injury levels to account for potential symptom exacerbation due to the TBI. The RPQ is the most commonly used clinical outcome measure for mild TBI research because it is simple and reflects psychosocial function. The RPQ is intended to measure the presence and severity of 16 of the most commonly reported post-concussion symptoms found in the literature.
- Neurobehavioral Symptom Inventory (NSI) [ Time Frame: Baseline randomization/Day 28/ Day 56 ] [ Designated as safety issue: No ]
The Neurobehavioral Symptom Inventory (NSI) is a self-report measure that asks individuals to rate their difficulties with a variety of symptoms.
Items on the Inventory include: Dizziness, loss of balance, poor coordination, headaches, nausea, visual disturbance, light sensitivity, hearing difficulty, noise sensitivity, body/extremity numbness, altered taste or smell, appetite change, poor concentration, forgetfulness, difficulty making decisions, slowed thinking, fatigue, insomnia, feeling anxious, feeling depressed, irritability and poor frustration tolerance.
|Study Start Date:||February 2011|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
No Intervention: Cohort 1 (PTSD) Group A
Subjects who have PTSD but have no diagnosed or suspected brain injuries
No Intervention: Cohort 2 (mTBI) Group B
Group B (mTBI LC) (randomized/unblinded): Subjects who have one or more mild traumatic brain injuries with persistent symptoms per the inclusion/exclusion criteria and are randomized to continue to receive local care for mTBI
Experimental: Cohort 2 (mTBI) Group C
Group C (mTBI HBO2) (randomized/blinded): Subjects who have one or more mild traumatic brain injuries with persistent symptoms per the inclusion/exclusion criteria and are randomized to the active intervention (hyperbaric oxygen)
Drug: hyperbaric oxygen
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).
Other Name: medical oxygen
Sham Comparator: Cohort 2 (mTBI) Group D
Subjects who have one or more mild traumatic brain injuries with persistent symptoms per the inclusion/ exclusion criteria and are randomized to the sham control
Drug: hyperbaric oxygen
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 Name: medical oxygen
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01306968
|United States, California|
|Naval Hospital Camp Pendleton|
|Camp Pendleton, California, United States, 92055|
|United States, Colorado|
|Evans Army community Hospital Fort Carson|
|Fort Carson, Colorado, United States, 80913|
|United States, Georgia|
|Eisenhower Army Medical Center|
|Fort Gordon, Georgia, United States, 30905|
|United States, North Carolina|
|Naval Hospital Camp Lejeune|
|Camp Lejeune, North Carolina, United States, 28547|
|United States, Utah|
|Study Coordinating Center, LDS Hospital|
|Salt lake City, Utah, United States, 84143|
|Principal Investigator:||Scott Miller, MD, COL||United States Army Medical Materiel Development Activity|