A Pilot Phase II Study of Hyperbaric Oxygen for Persistent Post-concussive Symptoms After Mild Traumatic Brain Injury (HOPPS)
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.
Condition:
Post-concussive Symptoms
Treatment:
hyperbaric oxygen
Start Date:
February 2011
Sponsor:
U.S. Army Medical Research and Development Command
For More Information:
https://clinicaltrials.gov/show/NCT01306968