Clinical trial NCT00810615: Treatment of Traumatic Brain Injury With Hyperbaric Oxygen Therapy
Official title: Treatment of Moderate to Mild Cognitive Dysfunction Caused by Traumatic Brain Injury (TBI) With Hyperbaric Oxygen Therapy (HBOT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain Injury, Chronic
Keywords: chronic TBI
cognitive function
PTSD
HBO
hyperbaric
oxygen
chronic brain injury
Lead sponsor: San Antonio Military Medical Center
Sponsor class: FED
First posted: 2008-12-18
Enrollment: 50
Sex: ALL
Minimum age (years): 19
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if hyperbaric oxygen therapy (HBOT) improves the cognitive function of OIF/OEF individuals who have chronic mild to moderate traumatic brain injury (TBI). Cognitive function includes such things as thinking, remembering, recognition, concentration ability and perception. Traumatic brain injury is common with head injuries caused by blows to the head, nearby explosions, or concussion. Subjects will be assigned to an intervention or sham arm. Computer based cognitive tests will be used as outcome measures. Subjects are enrolled by invitation only.

Detailed description: The Agency for Healthcare Research and Quality (AHRQ) did a comprehensive review of the literature focusing on TBI, stroke and cerebral palsy in Sep 2003. The study design and goals were based on the AHRQ recommendations for future hyperbaric oxygen for TBI research. This report stated, "The most important gap in the evidence is a lack of a good quality time-series study or controlled trial of the effects of HBOT on cognition, memory, and functional status in patients with deficits due to mild and moderate chronic TBI." The AHRQ Evidence Report further stated, "Lack of agreement on the dosage of HBOT and the duration of treatment is an important barrier to conducting good-quality clinical studies...Good-quality dose-ranging studies of HBOT for brain injury can be done, based on the model used by pharmaceutical manufacturers and the FDA. It is likely that the dosage of HBOT needs to be individualized based on the patient's age, clinical condition, and other factors". Although there are many anecdotal cases of TBI improvement with HBO, this case is backed with non-subjective data. The biological basis for why breathing 100% oxygen under pressurized conditions improves chronic neurological trauma remains unclear. There is some evidence that chronic TBI effects are related to the demyelization effect linked to the expression of a specific protease, calpain. This protease is also seen in demyelination delayed effects of carbon monoxide poisoning which is slowed by treatment with HBO. The "idling neuron" theory advocated in neurological studies suggest that HBO may increase metabolic performance of chronically impaired neurons that were marginally capable, enabling restoration of full function leading in turn to increased integrative plasticity. HBO has been shown to increase recruitment of stem cells from the bone marrow, suggesting that HBO may increase the rate at which damaged neuronal tissue can be reconstituted de novo. The proposed research will treat 25 subjects using HBO (2.4 ATA breathing 100% oxygen) and 25 subjects in a sham HBO treatment (1.3 ATA breathing air). Computer-based cognitive testing and the Post-traumatic Stress Disorder Checklist for Military (PCL-M) will be administered pre- and post-HBOT as well as at intervals throughout the treatment. The cognitive test results and stem cell results will be analyzed within each subject at the various treatment points as well as cohort groups between each treatment leg. Cognitive test scores will also be compared to cognitive test population reference bases matched for gender and age. The Agency for Healthcare Research and Quality 2003 report also stated, "If there is a 1 percent chance that the treatment works, a rational decision maker would try it-there is a potential gain and no potential loss. On the other hand, if there are proven harms, and their severity and frequency are well described, the probability that the treatment works would have to be higher before most people would try it"

Eligibility criteria: Inclusion Criteria:

* neurology diagnosis of mild to moderate TBI
* injury sustained during OIF/OEF military activities
* perception of cognitive dysfunction following their injury
* stable mental status for at least two months
* stable psychotropic medication history for at least one month
* ability to perform computer based cognitive testing (must be capable using a mouse and PDA pointer and readily view the displays)
* TBI occurrence since 7 October 2001
* ability to consent

Exclusion Criteria:

* medical conditions that prevent subject from participating in hyperbaric environments
* previous hyperbaric oxygen treatments since being diagnosed with TBI
* history of alcohol abuse
* history of drug abuse

Primary outcomes:
measure: Computer Cognitive Test Scores - ImPACT Verbal Memory
timeFrame: Baseline and six weeks post hyperbaric exposure series
measure: Posttraumatic Stress Disorder Checklist - Military Version (PCL-M) Scores
timeFrame: baseline compared to the change at post hyperbaric exposures (30) series and the six weeks post hyperbaric exposure series
measure: Computer Cognitive Test Scores - ImPACT Visual Memory
timeFrame: Baseline and six weeks post hyperbaric exposure series
measure: Computer Cognitive Test Scores - ImPACT Processing Speed
timeFrame: Baseline and six weeks post hyperbaric exposure series
measure: Computer Cognitive Test Scores - ImPACT Reaction Time
timeFrame: Baseline and six weeks post hyperbaric exposure series
measure: Computer Cognitive Test Scores - BrainCheckers Simple Reaction Time
timeFrame: Baseline and six weeks post hyperbaric exposure series
measure: Computer Cognitive Test Scores - BrainCheckers Code Substitution
timeFrame: Baseline and six weeks post hyperbaric exposure series
measure: Computer Cognitive Test Scores - BrainCheckers Procedural Reaction Time
timeFrame: Baseline and six weeks post hyperbaric exposure series
measure: Computer Cognitive Test Scores - BrainCheckers Go-NoGo Reaction Time
timeFrame: Baseline and six weeks post hyperbaric exposure series
measure: Computer Cognitive Test Scores - BrainCheckers Matching To Sample
timeFrame: Baseline and six weeks post hyperbaric exposure series
measure: Computer Cognitive Test Scores - BrainCheckers Code Sub Recall
timeFrame: Baseline and six weeks post hyperbaric exposure series
Secondary outcomes:
measure: Functional MRI
timeFrame: six weeks post hyperbaric exposure series
measure: Stem Cells: CD_34
timeFrame: six weeks post hyperbaric exposure series
Other outcomes:
Locations:
Study officials:
affiliation: SAMMC Hyperbaric Medicine
name: E. George Wolf, M.D.
role: STUDY_DIRECTOR
affiliation: SAMMC Hyperbaric Medicine
name: Leonardo C Profenna, M.D.
role: PRINCIPAL_INVESTIGATOR
References: