Hyperbaric Oxygen Therapy (HBO2T) for Post-Concussive Symptoms (PSC) After Mild Traumatic Brain Injury (mTBI) (HBOT)

Hyperbaric Oxygen Therapy (HBO2T) for Post-Concussive Symptoms (PSC) After Mild Traumatic Brain Injury (mTBI): A Randomized, Double-Blinded, Sham Controlled, Variable Dose, Prospective Trial

The goal of this research is to serve as a demonstration project to determine the tolerability of individuals with persistent post-concussive symptoms from combat-related mild TBI (traumatic brain injury), identify dose-finding for HBO2 (Hyperbaric Oxygen) therapy, and determine the efficacy of HBO2 therapy.

Study Overview

• Status: Completed
• Conditions: Mild Traumatic Brain Injury; Post-Concussive Syndrome
• Intervention / Treatment: Procedure: Hyperbaric Oxygen Therapy; Procedure: Hyperbaric Oxygen Therapy; Procedure: Hyperbaric Oxygen Therapy

Detailed Description

Persistent post-concussive symptoms from mild traumatic brain injury are a severe issue facing the readiness, retention and quality of life of Department of Defense(DoD) service members and Veterans. The inadequacy of established treatment regimens and evidence-based science in post-concussive symptoms (PCS)/MTBI is forcing a closer look at non-conventional treatments of this condition. Hyperbaric oxygen (HBO2) is a potent intervention with demonstrated efficacy in dive-related injuries, soft tissue healing, and carbon monoxide poisoning.

This study is prospective, randomized, double-blinded and controlled. A total of 60 subjects will be randomly assigned to one of three treatment arms of the study: 20 subjects into the 1.5 atm abs oxygen equivalent HBO2 treatment, 20 subjects into the 2.0 atm abs oxygen equivalent HBO2 treatment and 20 subjects into the sham treatment (a placebo exposure equivalent to breathing atmospheric air). The protocol utilizes a pre- and post-treatment comprehensive performance battery that will allow for meaningful clinical outcomes and a broad understanding of the effects of the treatment. This project represents a collaboration between the Department of Defense (DoD), the Richmond Veterans Administration Medical Center (VAMC) and Virginia Commonwealth University. Service members will be recruited from military bases/treatment facilities (MTF), receive hyperbaric oxygen at existing DoD hyperbaric chambers and be evaluated by the established Virginia Commonwealth University-Center for Rehabilitation Sciences and Engineering (CERSE), a collaborative research center co-located at the Richmond VAMC and VCU.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Portsmouth, Virginia, United States
      • Naval Medical Center Portsmouth
    • Richmond, Virginia, United States
      • Virginia Commonwealth University
    • Richmond, Virginia, United States
      • Hunter Holmes McGuire Veterans' Affairs Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Post-Deployment status after having served in OIF/OEF
2. Blast Event within past 3 years during OIF/OEF deployment [event defined as any of the following symptoms or experiences occurring during or shortly after the blast or explosion: dazed, confused, saw stars, headache, dizziness, irritability, memory gap (not remembering injury or injury period), hearing loss, abdominal pain, shortness of breath, struck by debris, knocked over or down, knocked into or against something, helmet damaged, evacuated]
3. Diagnosis of MTBI within 3 years as confirmed by the TBI specialty team at the Richmond VAMC
4. Presence of post-concussive symptoms from MTBI, confirmed by the VCU-CERSE team at the Richmond VAMC, for at least 3 months
5. Medical clearance to undergo hyperbaric oxygen treatment
6. Stable mental status for at least one month
7. Stable psychotropic medication history for at least one month
8. Ability to perform neuropsychologic testing battery
9. Ability to tolerate neurophysiological and neuroimaging battery

Exclusion Criteria:

1. Traumatic Brain Injury with a primary etiology other than blast
2. Moderate or Severe TBI (moderate or severe brain injury defined as best Glasgow Coma Score in first 24 hours < 12, , brain bleeding or blood clot (i.e., abnormal brain CT scan), or none of first week after event can be remembered.)
3. Past history of moderate or severe TBI
4. Active diagnosis of Post-traumatic Stress Disorder
5. Active diagnosis of Generalized Anxiety Disorder
6. Active Psychosis
7. Past history of Schizophrenia
8. Pre-existing PCS
9. Previous hyperbaric oxygen treatments
10. Contraindications to HBO2, including any "air trapping" pulmonary problems, inability to equalize middle ear and sinuses, or patients who are claustrophobic and require anti-anxiety medication for the condition
11. Active use of cancer medications
12. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment 1--1.5 atm abs	Procedure: Hyperbaric Oxygen Therapy; 1.5 atm abs oxygen equivalent of 75% oxygen (balance 25% nitrogen), 40 treatments of 60 minutes each during a time period of up to ten weeks.; Procedure: Hyperbaric Oxygen Therapy; 2.0 atm abs oxygen equivalent of 100% oxygen (no nitrogen), 40 treatments of 60 minutes each during a time period of up to ten weeks.; Procedure: Hyperbaric Oxygen Therapy; sham--air equivalent of 10.5% oxygen (balance 89.5% nitrogen), 40 treatments of 60 minutes each during a time period of up to ten weeks.
EXPERIMENTAL: Treatment 2--2.0 atm abs	Procedure: Hyperbaric Oxygen Therapy; 1.5 atm abs oxygen equivalent of 75% oxygen (balance 25% nitrogen), 40 treatments of 60 minutes each during a time period of up to ten weeks.; Procedure: Hyperbaric Oxygen Therapy; 2.0 atm abs oxygen equivalent of 100% oxygen (no nitrogen), 40 treatments of 60 minutes each during a time period of up to ten weeks.; Procedure: Hyperbaric Oxygen Therapy; sham--air equivalent of 10.5% oxygen (balance 89.5% nitrogen), 40 treatments of 60 minutes each during a time period of up to ten weeks.
SHAM_COMPARATOR: Placebo--equivalent to breathing air	Procedure: Hyperbaric Oxygen Therapy; 1.5 atm abs oxygen equivalent of 75% oxygen (balance 25% nitrogen), 40 treatments of 60 minutes each during a time period of up to ten weeks.; Procedure: Hyperbaric Oxygen Therapy; 2.0 atm abs oxygen equivalent of 100% oxygen (no nitrogen), 40 treatments of 60 minutes each during a time period of up to ten weeks.; Procedure: Hyperbaric Oxygen Therapy; sham--air equivalent of 10.5% oxygen (balance 89.5% nitrogen), 40 treatments of 60 minutes each during a time period of up to ten weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement on symptom assessment battery	Symptom Assessment Battery include: Rivermead Postconcussive Symptom Questionnaire, Pain Intensity Numerical 0-10 scale, Alcohol Use Disorders Test-Consumption, McGill Pain Questionnaire-Short Form, The Center for Epidemiological Studies Depression Scale, PTSD Checklist-Military Version, Extended Glasgow Outcome Scale, Mayo-Portland Adaptability Inventory 4, Satisfaction With Life Scale	2-4 weeks before treatment
Improvement on symptom assessment battery	Symptom Assessment Battery include: Rivermead Postconcussive Symptom Questionnaire, Pain Intensity Numerical 0-10 scale, Alcohol Use Disorders Test-Consumption, McGill Pain Questionnaire-Short Form, The Center for Epidemiological Studies Depression Scale, PTSD Checklist-Military Version, Extended Glasgow Outcome Scale, Mayo-Portland Adaptability Inventory 4, Satisfaction With Life Scale	24-72 hours after final treatment
Improvement on symptom assessment battery	Symptom Assessment Battery include: Rivermead Postconcussive Symptom Questionnaire, Pain Intensity Numerical 0-10 scale, Alcohol Use Disorders Test-Consumption, McGill Pain Questionnaire-Short Form, The Center for Epidemiological Studies Depression Scale, PTSD Checklist-Military Version, Extended Glasgow Outcome Scale, Mayo-Portland Adaptability Inventory 4, Satisfaction With Life Scale	3 months after final treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological Testing Battery	Test Battery Includes: Trail Making Test, Stroop Classic, California Verbal Learning Test-II, Wechsler Test of Adult Reading, Wechsler Adult Intelligence Scale III (WAIS-III): Digit Symbol Coding Digit Span Letter-Number Sequencing Symbol Search and Arithmetic, Delis-Kaplan Executive Functioning System(D-KEFS): Controlled Oral Word Exam (COWA), Grooved Pedboard, Test of Memory Malingering, Benton Visual Memory Test-Revised	2-4 weeks before treatment
Neurophysiologic Measures of Human Performance: Computerized Posturography, NeuroImaging and Eye tracking		24-72 hours after final treatment
Common Military Task Tests	Testing includes: Mission-oriented protective posture (MOPP) gear donning, Protective mask usage, personal weapon assembly/dis-assembly, grenade inspection/identification, acute management of injury-induced shock	2-4 weeks before treatment
Neuropsychological Testing Battery	Test Battery Includes: Trail Making Test, Stroop Classic, California Verbal Learning Test-II, Wechsler Test of Adult Reading, Wechsler Adult Intelligence Scale III (WAIS-III): Digit Symbol Coding Digit Span Letter-Number Sequencing Symbol Search and Arithmetic, Delis-Kaplan Executive Functioning System(D-KEFS): Controlled Oral Word Exam (COWA), Grooved Pedboard, Test of Memory Malingering, Benton Visual Memory Test-Revised	24-72 hours after final treatment
Neurophysiologic Measures of Human Performance: Computerized Posturography, NeuroImaging, Eye tracking		3 months after final treatment.
Neuropsychological Testing Battery	Test Battery Includes: Trail Making Test, Stroop Classic, California Verbal Learning Test-II, Wechsler Test of Adult Reading, Wechsler Adult Intelligence Scale III (WAIS-III): Digit Symbol Coding Digit Span Letter-Number Sequencing Symbol Search and Arithmetic, Delis-Kaplan Executive Functioning System(D-KEFS): Controlled Oral Word Exam (COWA), Grooved Pedboard, Test of Memory Malingering, Benton Visual Memory Test-Revised	3 months after final treatment.
Neurophysiologic Measures of Human Performance: Computerized Posturography, NeuroImaging, Eye tracking		2-4 weeks before treatment
Common Military Task Tests	Testing includes: Mission-oriented protective posture (MOPP) gear donning, Protective mask usage, personal weapon assembly/dis-assembly, grenade inspection/identification, acute management of injury-induced shock	24-72 hours after final treatment
Common Military Task Tests	Testing includes: Mission-oriented protective posture (MOPP) gear donning, Protective mask usage, personal weapon assembly/dis-assembly, grenade inspection/identification, acute management of injury-induced shock	3 months after final treatment.

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: United States Naval Medical Center, Portsmouth; Hunter Holmes Mcguire Veteran Affairs Medical Center
• Investigators: Principal Investigator: David X Cifu, MD, Virginia Commonwealth University; Principal Investigator: Brett Hart, MD, Naval Operational Medicine Institute; Principal Investigator: Michelle Nichols, MSN, RN, McGuire Veterans' Affairs Medical Center; Study Director: Justin O Alicea, Virginia Commonwealth University; Study Director: Steven L West, PhD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): July 1, 2013
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: October 6, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (ESTIMATE): October 14, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): August 27, 2013
• Last Update Submitted That Met QC Criteria: August 26, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Veterans; Traumatic Brain Injury; Post-Concussive Symptoms; OEF/OIF; Hyperbaric Oxygen Treatment; Blast Exposure
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Post-Concussion Syndrome; Brain Concussion
• Other Study ID Numbers: N66001-09-2-2060; 01609 (OTHER: Hunter Holmes McGuire Veterans' Affairs Medical Center); NOMI.2010.002 (OTHER: Naval Operational Medical Institute); HM12204 (OTHER: Virginia Commonwealth University)