Treatment of Traumatic Brain Injury With Hyperbaric Oxygen Therapy

Treatment of Moderate to Mild Cognitive Dysfunction Caused by Traumatic Brain Injury (TBI) With Hyperbaric Oxygen Therapy (HBOT)

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.

Study Overview

• Status: Completed
• Conditions: Brain Injury, Chronic
• Intervention / Treatment: Other: Sham treatment; Other: Hyperbaric oxygen @ 2.4 ATA

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"

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham treatment; Subject will breathe air at less than 1.3 Atmospheres Absolute (ATA) in three 30 minute periods separated by 10 minutes of breathing air at less that 1.3 ATA. Hyperbaric exposures will be done up to 5 times per week with a total number of 30 exposures.	Other: Sham treatment; Other Names: sham exposure; 1.3 ATA air
Experimental: Hyperbaric oxygen 2.4 ATA; Subject will breathe 100% oxygen at 2.4 Atmospheres Absolute (ATA) in three 30 minute periods separated by 10 minutes of breathing air at 2.4 ATA. Hyperbaric exposures will be done up to 5 times per week with a total number of 30 exposures.	Other: Hyperbaric oxygen @ 2.4 ATA; Subject will breath 100% oxygen at 2.4 Atmospheres Absolute (ATA) in three 30 minute periods separated by 10 minutes of breathing air at 2.4 ATA. Hyperbaric exposures will be done up to 5 times per week with a total number of 30 exposures.; Other Names: HBOT; HBO; hyperbaric oxygen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Computer Cognitive Test Scores - ImPACT Verbal Memory	The Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery was developed at the University of Pittsburgh. It has a sensitivity of 81.9% and specificity of 89.4% in discriminating between concussion and non-concussion groups. It consists of a medical history questionnaire regarding concussions and resultant symptoms including loss of consciousness, memory loss, confusion, headache, seizure activity, emotional state, and sleep patterns. There are four subtests given and scored by computer. These include verbal and visual memory, visual motor speed, and response time. The composite scores are specifically designed to determine changes within the individual, better or worse, over time. The verbal memory score demonstrates improvement as the score increases. The score range was 36.8 to 98.6.	Baseline and six weeks post hyperbaric exposure series
Posttraumatic Stress Disorder Checklist - Military Version (PCL-M) Scores	The PCL-M is a self reported test in which a list of 17 problems and complaints are offered to the individual to score on a 1 to 5 scale with 1 designating "not at all", 2= "a little bit", 3= "moderately", 4= "quite a bit" and 5 designating "extremely". A sample complaint would be "repeated, disturbing dreams of a stressful military experience". Hence there is a possible total score range from 17 to 85. For military members, a score of 50 or above is indicative of PTSD. A change from baseline of 5-9 represents a reliable change and change of 10 or greater is a significant change.	baseline compared to the change at post hyperbaric exposures (30) series and the six weeks post hyperbaric exposure series
Computer Cognitive Test Scores - ImPACT Visual Memory	The Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery was developed at the University of Pittsburgh. It has a sensitivity of 81.9% and specificity of 89.4% in discriminating between concussion and non-concussion groups. It consists of a medical history questionnaire regarding concussions and resultant symptoms including loss of consciousness, memory loss, confusion, headache, seizure activity, emotional state, and sleep patterns. There are four subtests given and scored by computer. These include verbal and visual memory, visual motor speed, and response time. The composite scores are specifically designed to determine changes within the individual, better or worse, over time. The visual memory score demonstrates improvement as the score increases. The score range was 31.2 to 92.7.	Baseline and six weeks post hyperbaric exposure series
Computer Cognitive Test Scores - ImPACT Processing Speed	The Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery was developed at the University of Pittsburgh. It has a sensitivity of 81.9% and specificity of 89.4% in discriminating between concussion and non-concussion groups. It consists of a medical history questionnaire regarding concussions and resultant symptoms including loss of consciousness, memory loss, confusion, headache, seizure activity, emotional state, and sleep patterns. There are four subtests given and scored by computer. These include verbal and visual memory, visual motor speed, and response time. The composite scores are specifically designed to determine changes within the individual, better or worse, over time. The Processing Speed score demonstrates improvement as the score increases. The score range was 9.7 to 52.4.	Baseline and six weeks post hyperbaric exposure series
Computer Cognitive Test Scores - ImPACT Reaction Time	The Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery was developed at the University of Pittsburgh. It has a sensitivity of 81.9% and specificity of 89.4% in discriminating between concussion and non-concussion groups. It consists of a medical history questionnaire regarding concussions and resultant symptoms including loss of consciousness, memory loss, confusion, headache, seizure activity, emotional state, and sleep patterns. There are four subtests given and scored by computer. These include verbal and visual memory, visual motor speed, and response time. The composite scores are specifically designed to determine changes within the individual, better or worse, over time. The reaction time score demonstrates improvement as the score decreases. The score range was 0.42 to 1.84.	Baseline and six weeks post hyperbaric exposure series
Computer Cognitive Test Scores - BrainCheckers Simple Reaction Time	Braincheckers is a PDA version of the Automated Neuropsychological Assessment Metrics (ANAM) supported by the Army Medical Research and Materiel Command in 2000. It was validated against ANAM for the individual tests used. Throughput is defined as correct responses per minute of time available to respond. Higher scores indicate higher accuracy in each of the subtest. The simple reaction time range is 30 to 255.	Baseline and six weeks post hyperbaric exposure series
Computer Cognitive Test Scores - BrainCheckers Code Substitution	Braincheckers is a PDA version of the Automated Neuropsychological Assessment Metrics (ANAM) supported by the Army Medical Research and Materiel Command in 2000. It was validated against ANAM for the individual tests used. Throughput is defined as correct responses per minute of time available to respond. Higher scores indicate higher accuracy in each of the subtest. The range is 9 to 66. The scores in this section represent results of the code substitution subtest.	Baseline and six weeks post hyperbaric exposure series
Computer Cognitive Test Scores - BrainCheckers Procedural Reaction Time	Braincheckers is a PDA version of the Automated Neuropsychological Assessment Metrics (ANAM) supported by the Army Medical Research and Materiel Command in 2000. It was validated against ANAM for the individual tests used. Throughput is defined as correct responses per minute of time available to respond. Higher scores indicate higher accuracy in each of the subtest. The range is 25 to 118. The scores in this section represent results of the procedural reaction time.	Baseline and six weeks post hyperbaric exposure series
Computer Cognitive Test Scores - BrainCheckers Go-NoGo Reaction Time	Braincheckers is a PDA version of the Automated Neuropsychological Assessment Metrics (ANAM) supported by the Army Medical Research and Materiel Command in 2000. It was validated against ANAM for the individual tests used. Throughput is defined as correct responses per minute of time available to respond. Higher scores indicate higher accuracy in each of the subtest. The range is 41 to 174. The scores in this section represent results of the Go-NoGo reaction time subtest.	Baseline and six weeks post hyperbaric exposure series
Computer Cognitive Test Scores - BrainCheckers Matching To Sample	BrainCheckers is a PDA version of the Automated Neuropsychological Assessment Metrics (ANAM) supported by the Army Medical Research and Materiel Command in 2000. It was validated against ANAM for the individual tests used. Throughput is defined as correct responses per minute of time available to respond. Higher scores indicate accuracy in each of the subtest. The range is 6 to 50. The scores in this section represent results of the matching to sample subtest.	Baseline and six weeks post hyperbaric exposure series
Computer Cognitive Test Scores - BrainCheckers Code Sub Recall	BrainCheckers is a PDA version of the Automated Neuropsychological Assessment Metrics (ANAM) supported by the Army Medical Research and Materiel Command in 2000. It was validated against ANAM for the individual tests used. Throughput is defined as correct responses per minute of time available to respond. Higher scores indicate accuracy in each of the subtest. The range is 6 to 135. The scores in this section represent results of the code sub recall subtest.	Baseline and six weeks post hyperbaric exposure series

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional MRI		six weeks post hyperbaric exposure series
Stem Cells: CD_34	A non-parametric regression 14 using the Theil estimator was fit to the observed data in order to demonstrate general trends for relations between measures of cognitive functioning and increased stem cells.	six weeks post hyperbaric exposure series

Collaborators and Investigators

• Sponsor: San Antonio Military Medical Center
• Investigators: Study Director: E. George Wolf, M.D., SAMMC Hyperbaric Medicine; Principal Investigator: Leonardo C Profenna, M.D., SAMMC Hyperbaric Medicine

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: December 17, 2008
• First Submitted That Met QC Criteria: December 17, 2008
• First Posted (Estimate): December 18, 2008

Study Record Updates

• Last Update Posted (Actual): August 13, 2018
• Last Update Submitted That Met QC Criteria: November 22, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: PTSD; cognitive function; oxygen; hyperbaric; HBO; chronic TBI; chronic brain injury
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Damage, Chronic; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Brain Injury, Chronic
• Other Study ID Numbers: FWH20080137H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No