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BIMA: mTBI Mechanisms of Action of HBO2 for Persistent Post-Concussive Symptoms

Sponsor
U.S. Army Medical Research and Development Command (U.S. Fed)
Overall Status
Completed
CT.gov ID
NCT01611194
Collaborator
(none)
71
Enrollment
5
Locations
2
Arms
40.6
Actual Duration (Months)
14.2
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Purpose of this study is to investigate the mechanisms of action of hyperbaric oxygen therapy for persistent post-concussive symptoms after mild tramatic brain injury

Condition or Disease Intervention/Treatment Phase
  • Drug: Hyperbaric oxygen (HBO2) at 1.5 atms
  • Drug: Sham control 1.2 atms
 Phase 2

Detailed Description

Active duty military personnel and Veterans received for 60-minute daily chamber sessions in which they received HBO2, 1.5 atmospheres absolute (ATA), or sham intervention (1.2 ATA, room air) for post concussion syndrome (PCS).

The study is to provide a rationale for the selection of outcome assessments to serve as primary and secondary endpoints for a pivotal randomized clinical trial of hyperbaric oxygen for the treatment of PCS. The participants will undergo a comprehensive battery of symptom and quality of life assessments. The distribution of response, change in response over time, homogeneity of variance across subgroups, and relationships between outcome measures will be compared by treatment assignment with a cohort from a study of similar design among a normal study population.

Study Design

Study Type:
Interventional
Actual Enrollment :
71 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
Brain Injury and Mechanisms of Action of HBO2 for Persistent Post-Concussive Symptoms After Mild Traumatic Brain Injury (BIMA) Protocol
Actual Study Start Date :
Sep 11, 2012
Actual Primary Completion Date :
Jan 1, 2015
Actual Study Completion Date :
Jan 29, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: HBO2 at 1.5 Atomspheres Absolute (ATA)

Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization.

Drug: Hyperbaric oxygen (HBO2) at 1.5 atms
The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week.
Other Names:
  • 1.5 atms

    		•
    Sham Comparator: Sham Control (1.2 Atomspheres)

    Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).

    Drug: Sham control 1.2 atms
    The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Other Names:
  • 1.2 atms (shame)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Summary of Treatment-Emergent Adverse Events [months 3, 6, 4, 5 and 7-12. Extended f/u up to 36 months]

      Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.

    2. Summary of Study Intervention-Related Adverse Events [months 3, 6, 4, 5 and 7-12. Extended f/u up to 36 months]

      Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.

    Secondary Outcome Measures

    1. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (ITT Population) [Baseline]

      RPQ/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-3 and RPQ-13 domain scores are presented separately. For each of the RPQ-3, RPQ-13, and RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain.

    2. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (Per Protocol (PP) Population) [Baseline]

      RPQ/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-3 and RPQ-13 domain scores are presented separately. For each of the RPQ-3, RPQ-13, and RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain.

    3. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (ITT Population) [Baseline to week 13, Months 6 and 12]

      RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. The scores were derived by totaling the corresponding question scores for each domain and it's change from baseline.

    4. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (ITT Population) [Baseline to week 13, Months 6 and 12]

      RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. Analyses of the RPQ-3 domain scores are presented separately. For the RPQ-3 total scales, the scores were derived by totaling the corresponding question scores for each domain and it's change from baseline.

    5. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (ITT Population) [Baseline to week 13, Months 6 and 12]

      RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. For RPQ-13 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

    6. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population) [Baseline to week 13, Months 6 and 12]

      RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. For the RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

    7. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population) [Baseline to week 13, Months 6 and 12]

      RPQ/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. For the RPQ-3total scale, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

    8. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population) [Baseline to week 13, Months 6 and 12]

      RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. The scores were derived by totaling the corresponding question scores for each domain and change from baseline.

    9. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline: 24 and 36 Months (ITT Population) [Baseline to 24 months and 36 months]

      RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. For the RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

    10. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline: 24 and 36 Months (ITT Population) [Baseline to 24 months and 36 months]

      RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. Analyses of the RPQ-3 domain scores are presented separately. For the RPQ-3 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

    11. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline: 24 and 36 Months (ITT Population) [Baseline to 24 months and 36 months]

      RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. For RPQ-13 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

    12. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population) [Baseline to month 24 and month 36]

      RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. For the RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

    13. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population) [Baseline to month 24 and month 36]

      RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. Analyses of the RPQ-3 domain scores are presented separately. For the RPQ-3 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.

    14. Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population) [Baseline to month 24 and month 36]

      RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. For RPQ-13 total scales, the scores were derived by totaling the corresponding question scores for each domain change from baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • On active duty (TRICARE beneficiary) at the time of consent and through the 6-month visit or a Veteran, as well as Active Duty military who become Veterans after enrollment.

    • Men and women 18-65 years of age at the time of study enrollment.

    • Able to equalize middle ear pressure in a test of chamber pressure and tolerate the chamber environment.

    • Able to speak and read English, as primary language.

    • Agrees to and appears able to participate in all outcome assessments.

    • Agrees to provide blood samples for clinical lab tests.

    • Demonstrates the ability to offer informed consent and signs the study informed consent document.

    • Participants stationed or living outside the Colorado Springs/Denver, Colorado area must be willing and able to travel. A reliable companion may accompany the participant if travel supervision is required.

    • Active duty participants must obtain a letter of support from a supervisor or commanding officer prior to the outcome assessments (and travel, if necessary) to the OAC.

    Participants must have a history of at least one (minimum requirement) mild traumatic brain injury (mTBI) with persistent symptoms that meets all the following criteria:

    • Brain injury that occurred more than 3 months prior to baseline screening at the local site, with the most recent injury occurring no more than 5 years prior to randomization.

    • Most recent traumatic brain injury (TBI) occurred on active duty.

    • TBI was caused by non-penetrating trauma or blast exposure.

    • TBI resulted in at least one of the following at the time of injury: a period of loss of or a decreased level of consciousness (up to 30 minutes); a loss of memory for events immediately before or after the injury (up to 24 hours); or alteration in mental state at the time of the injury (becoming dazed or confused).

    • Has current complaints of TBI symptoms such as headache, dizziness, or cognitive or affective problems that score at least 3 post-concussive symptoms as assessed by the OSU TBI-ID.

    • Has received current standard of care pharmacologic and nonpharmacologic interventions for TBI and any concomitant post traumatic stress disorder (PTSD) with no significant change in psychoactive therapy for at least 1 month.

    • Creatinine level that is less than or equal to the EACH laboratory's upper limit of normal. If the creatinine level exceeds the EACH laboratory's upper limit of normal, participants cannot have a CT scan due to risk of contrast dye-induced renal failure. Such participants may be randomized but must be approved by the Study Director.

    Exclusion Criteria:

    • Prisoners.

    • Pregnant Women.

    • Minors.

    • Individuals whose most recent TBI was sustained during illegal activity.

    • Potential active duty participants stationed >1 hour outside the designated recruitment area of a participating local site will be excluded unless the command authorizes temporary relocation and appropriate relocation resources.

    • Potential Veteran participants who live >1 hour outside the designated recruitment area of a participating local site, must be willing and able to travel to the local site to participate in all required local site visits without additional financial assistance than that which is described in the Veteran Payment Schedule (consent attachment C).

    • Active duty individuals with anticipated prolonged TAD/TDY or deployment within 6 months of study enrollment will be excluded.

    • Veterans with anticipated prolonged travel or relocation within 6 months of study enrollment will be excluded.

    An individual with any of the following characteristics will be excluded from this study based on contraindications to hyperbaric pressurization and hyperbaric oxygenation or other study assessment measures:

    • Women who are pregnant or who plan to become pregnant during the study period.

    • Women who are breastfeeding.

    • Women of childbearing potential who do not agree to practice an acceptable form of birth control during the study period.

    • Epilepsy or seizure disorder not stable on anticonvulsant therapy (stable defined as 6 months seizure-free).

    • Inability to protect airway or requires frequent suctioning.

    • Known or suspected perilymphatic fistula.

    • Presence of tracheostomy (due to limitations in autoinflation of the middle ear space).

    • Diabetes (risk of hypoglycemia).

    • Creatinine level that exceeds 1.5 times the EACH laboratory's upper limit of normal.

    • A diagnosis (from patient report or medical record evidence within one year) of untreated clinical hypo- or hyperthyroidism.

    • Allergy to iodine-based contrast dye (exclusion criteria for neuroimaging assessment measures only).

    • Presence of implanted device (e.g., cardiac defibrillator, intrathecal drug delivery device, cochlear implant, pacemaker, stents or aneurysm clips) that poses increased risk to the participant during hyperbaric exposure or magnetic resonance imaging (MRI). Any implanted device must be cleared through the manufacturer for exposure to hyperbaric pressure and 3.0 Tesla MRI.

    • Participants who must travel to altitudes greater than 10,000 feet during chamber session intervention.

    • Paratroopers who are unable to suspend activity during chamber exposures.

    • An individual who has had refractive eye surgery within the last 90 days.

    • Any brain injury not of traumatic etiology, such as stroke or drug-induced coma.

    • Heart failure with ejection fraction < 50% (due to increased risk for precipitating acute lung edema during exposure to HBO2).

    • Emphysema, chronic bronchitis, or bullous lung disease (due to risk for pulmonary barotrauma during hyperbaric decompression).

    • Asthma not well controlled.

    An individual with any of the following characteristics will be excluded from this study based on confounding of the outcome measures:

    • Those who are unable to participate fully in outcome assessments unless randomization is reviewed and approved (in writing) by the study director.

    • Vision uncorrectable to 20/50 (monocular vision acceptable).

    • Dynavision within 30 days of screening.

    • Deafness in both ears defined as 90 dB HL or greater, through the speech frequencies of each of 500 Hz, 1 kHz, 2 kHz and 4 kHz in each ear; this is determined by a baseline measurement of pure tone air conduction thresholds.

    • Participant self-report or documented diagnosis of psychiatric disorders in the medical record within the last year of any of the following: schizophrenia, dissociative disorder, or bipolar disease.

    • Anxiety or claustrophobia precluding participation in the hyperbaric chamber sessions or neuroimaging procedures.

    • Verifiable neurodegenerative disease (e.g., Alzheimer's disease, multiple sclerosis, senile dementia).

    • Presence of chronic debilitating disease (e.g., end-stage renal disease, end-stage liver disease, diabetes with sequelae).

    • Documented unresolved anemia, with anemia defined as hematocrit less than 30%.

    • History, by self-report, of receiving therapeutic ionizing radiation to the head.

    • Foreign material in head that would interfere with brain imaging (e.g., MRI or computed tomography [CT]), unless randomization has been cleared by the study director.

    • Foreign (unknown composition) or metallic/ferromagnetic material within the individual that poses risk from MRI, unless randomization has been cleared by the study director.

    • History, by self report, of illicit drug use, except remote (prior to military enlistment) non-habitual (habitual is considered greater than weekend) use of marijuana.

    • History, by self report or medical record in the last year, of alcohol abuse. Prospective participants who have been sober for the last 90 days prior to screening may be eligible based on the site principal investigator determination.

    • Current positive urine test for an illicit substance(s).

    • Any condition or use of prescribed medication in which, in the opinion of the investigator, participation in this study would impact the safety of the individual.

    • Brain injury of moderate or severe degree: duration of loss of consciousness at the time of injury greater than 30 minutes, duration of post-traumatic amnesia greater than 24 hours, or brain injury of a penetrating etiology.

    • Any lifetime history of penetrating brain injury.

    • Active malignancy, prior malignancy (except basal cell carcinoma) within the last 5 years, or any prior treatment with bleomycin (trade name Blenoxane). Prior treatment with doxorubicin (trade name Adriamycin) is acceptable as long as an echocardiography following treatment is normal.

    • Unable to abstain from caffeine or tobacco products for at least a 2-hour interval.

    • Concurrent enrollment in an alternate interventional trial.

    • Unable or unwilling to cease participation in sports in which another head injury is likely (e.g., mixed martial arts, boxing) during the study period.

    • Diagnosis of Meniere's disease by self-report or medical record evidence within one year.

    • Pre-TBI history of significant dizziness (lasting more than 1 day).

    A prospective participant with any of the following characteristics will be excluded from this study to protect blinding:

    • Prior treatment with HBO2 for TBI or PCS.

    • Prior HBO2 treatment for indications other than TBI or PCS within the last 3 months.

    • Experienced hyperbaric chamber inside attendant (anyone deemed to have experience with hyperbaric pressurization that could compromise their blind to allocation).

    • Technical, military, or occupational divers.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Outcomes Assessment Center, Evans Army Community Hospital Colorado Springs Colorado United States 80913
    2 Evans Army Community Hospital / Hyperbaric Medicine Complex Fort Carson Colorado United States 80913
    3 Camp Lejeune Jacksonville North Carolina United States 28542
    4 Joint Base Lewis-McChord Fort Lewis Washington United States 98438
    5 TBI Program/HBO2 Research Program Madigan Healthcare system Tacoma Washington United States 98431

    Sponsors and Collaborators

    • U.S. Army Medical Research and Development Command

    Investigators

    • Principal Investigator: Lindell Weaver, MD, Intermountain Health Care, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    U.S. Army Medical Research and Development Command
    ClinicalTrials.gov Identifier:
    NCT01611194
    Other Study ID Numbers:
    • S-11-17
    First Posted:
    Jun 4, 2012
    Last Update Posted:
    Nov 21, 2018
    Last Verified:
    Oct 1, 2018
    Keywords provided by U.S. Army Medical Research and Development Command
    HBO2
    HBOT
    mTBI
    Brain injury
    PCS
    PTSD
    hyperbaric oxygen
    Additional relevant MeSH terms:
    Brain Injuries
    Brain Injuries, Traumatic
    Post-Concussion Syndrome
    Unconsciousness
    Wounds and Injuries

    Study Results

    Participant Flow

    Recruitment Details Participants were recruited from military sites from Sept 2012 to May 2014.
    Pre-assignment Detail
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Period Title: Overall Study
    STARTED 36 35
    COMPLETED 36 32
    NOT COMPLETED 0 3

    Baseline Characteristics

    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres) Total
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Total of all reporting groups
    Overall Participants 36 35 71
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    34.8
    (8.3)
    30.8
    (5.5)
    32.8
    (7.3)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    1
    2.9%
    1
    1.4%
    Male
    36
    100%
    34
    97.1%
    70
    98.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    7
    19.4%
    6
    17.1%
    13
    18.3%
    Not Hispanic or Latino
    29
    80.6%
    29
    82.9%
    58
    81.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    1
    2.9%
    1
    1.4%
    Native Hawaiian or Other Pacific Islander
    2
    5.6%
    2
    5.7%
    4
    5.6%
    Black or African American
    2
    5.6%
    2
    5.7%
    4
    5.6%
    White
    30
    83.3%
    28
    80%
    58
    81.7%
    More than one race
    0
    0%
    1
    2.9%
    1
    1.4%
    Unknown or Not Reported
    2
    5.6%
    1
    2.9%
    3
    4.2%
    Region of Enrollment (Count of Participants)
    United States
    36
    100%
    35
    100%
    71
    100%
    Education (Count of Participants)
    Less than high school diploma
    0
    0%
    0
    0%
    0
    0%
    High school diploma
    7
    19.4%
    6
    17.1%
    13
    18.3%
    Some college
    13
    36.1%
    23
    65.7%
    36
    50.7%
    College degree
    11
    30.6%
    5
    14.3%
    16
    22.5%
    Graduare degree
    5
    13.9%
    1
    2.9%
    6
    8.5%
    Military Status (Count of Participants)
    Active duty
    35
    97.2%
    33
    94.3%
    68
    95.8%
    Veteran
    1
    2.8%
    2
    5.7%
    3
    4.2%
    Time From Most Recent Qualifying Mild Traumatic Brain Injury (mTBI) (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    25.6
    (17.1)
    25.5
    (15.4)
    25.6
    (16.2)
    Most Recent Qualifying mTBI 3 Months to 1 Year (Count of Participants)
    3 months to 1 year
    12
    33.3%
    8
    22.9%
    20
    28.2%
    >1year to 5 years
    24
    66.7%
    27
    77.1%
    51
    71.8%
    Number of Lifetime mTBIs (mTBIs) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mTBIs]
    3.6
    (3.2)
    3.7
    (2.3)
    3.6
    (2.8)
    Lifetime mTBI History (Count of Participants)
    Blast injuries
    15
    41.7%
    8
    22.9%
    23
    32.4%
    Blunt force head injuries only
    7
    19.4%
    7
    20%
    14
    19.7%
    Combination of blast and blunt force injuries
    14
    38.9%
    20
    57.1%
    34
    47.9%
    Most Recent Qualifying Injury (Count of Participants)
    Blast injury
    23
    63.9%
    23
    65.7%
    46
    64.8%
    Blunt force head injury
    13
    36.1%
    12
    34.3%
    25
    35.2%
    Military Rank (Count of Participants)
    E1-E10
    31
    86.1%
    35
    100%
    66
    93%
    O-1 to O-10/W-1 to W-5
    5
    13.9%
    0
    0%
    5
    7%
    Military Branch (Count of Participants)
    Army
    27
    75%
    28
    80%
    55
    77.5%
    Marines
    7
    19.4%
    5
    14.3%
    12
    16.9%
    Navy, Air Force, and Coast Guard
    2
    5.6%
    2
    5.7%
    4
    5.6%
    Number of Combat Deployments (deployments) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [deployments]
    3.4
    (2.8)
    2.2
    (1.7)
    2.8
    (2.4)
    Common Medication Usage (participants) [Number]
    SSRI/SNRIs
    12
    33.3%
    10
    28.6%
    22
    31%
    Hypnotic or sleep aid
    16
    44.4%
    15
    42.9%
    31
    43.7%
    Daily pain medication
    22
    61.1%
    21
    60%
    43
    60.6%
    Episodic migraine medication
    16
    44.4%
    14
    40%
    30
    42.3%
    Fish oil or omega-3 fatty acid
    9
    25%
    8
    22.9%
    17
    23.9%
    Common Alternative Therapy Usage (participants) [Number]
    Psychotherapy
    12
    33.3%
    7
    20%
    19
    26.8%
    Counseling
    16
    44.4%
    12
    34.3%
    28
    39.4%
    Physical therapy
    14
    38.9%
    20
    57.1%
    34
    47.9%

    Outcome Measures

    1. Primary Outcome
    Title Summary of Treatment-Emergent Adverse Events
    Description Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
    Time Frame months 3, 6, 4, 5 and 7-12. Extended f/u up to 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 36 35
    Barotitis media
    13
    36.1%
    5
    14.3%
    Sinus barotrauma
    5
    13.9%
    3
    8.6%
    Contusion
    3
    8.3%
    3
    8.6%
    Ligament sprain
    0
    0%
    5
    14.3%
    Muscle strain
    1
    2.8%
    3
    8.6%
    Upper respiratory tract infection
    13
    36.1%
    9
    25.7%
    Gastroenteritis
    1
    2.8%
    5
    14.3%
    Sinusitis
    3
    8.3%
    4
    11.4%
    Nasopharyngitis
    3
    8.3%
    2
    5.7%
    Arthralgia
    4
    11.1%
    2
    5.7%
    Back pain
    3
    8.3%
    2
    5.7%
    Neck pain
    0
    0%
    4
    11.4%
    Dizziness
    5
    13.9%
    1
    2.9%
    Headache
    4
    11.1%
    2
    5.7%
    Nasal congestion
    5
    13.9%
    3
    8.6%
    Dyspnea
    4
    11.1%
    1
    2.9%
    Epistaxis
    2
    5.6%
    2
    5.7%
    Sinus congestion
    2
    5.6%
    2
    5.7%
    Eye disorders
    10
    27.8%
    7
    20%
    Nausea
    4
    11.1%
    1
    2.9%
    Suicidal ideation
    2
    5.6%
    2
    5.7%
    Rash
    0
    0%
    3
    8.6%
    Investigations
    4
    11.1%
    3
    8.6%
    Vertigo
    3
    8.3%
    3
    8.6%
    General and administration site conditions
    3
    8.3%
    1
    2.9%
    Metabolism and nutrition disorders
    3
    8.3%
    2
    5.7%
    Renal and urinary disorders
    3
    8.3%
    0
    0%
    Vascular disorders
    3
    8.3%
    0
    0%
    Congenital, familial and genetic disorders
    1
    2.8%
    0
    0%
    Endocrine disorders
    1
    2.8%
    0
    0%
    Hepatobiliary disorders
    1
    2.8%
    0
    0%
    Immune system disorders
    0
    0%
    1
    2.9%
    Neoplasms benign, malignant and unspecified
    0
    0%
    1
    2.9%
    2. Primary Outcome
    Title Summary of Study Intervention-Related Adverse Events
    Description Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
    Time Frame months 3, 6, 4, 5 and 7-12. Extended f/u up to 36 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 36 35
    Barotitis media
    11
    30.6%
    5
    14.3%
    Sinus barotrauma
    5
    13.9%
    4
    11.4%
    Dizziness
    1
    2.8%
    1
    2.9%
    Headache
    1
    2.8%
    2
    5.7%
    Somnolence
    1
    2.8%
    1
    2.9%
    Dyspnea
    2
    5.6%
    0
    0%
    Hyperventilation
    1
    2.8%
    0
    0%
    Anxiety
    1
    2.8%
    0
    0%
    Myopia
    1
    2.8%
    1
    2.9%
    Eye pruritus
    0
    0%
    1
    2.9%
    Vertigo
    1
    2.8%
    1
    2.9%
    3. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (ITT Population)
    Description RPQ/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-3 and RPQ-13 domain scores are presented separately. For each of the RPQ-3, RPQ-13, and RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain.
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 36 35
    RPQ Total Score
    34.8
    (13.1)
    28.2
    (13.5)
    RPQ-3 Score
    5.8
    (2.9)
    4.5
    (2.6)
    RPQ-13 Score
    29.0
    (11.0)
    23.7
    (11.4)
    4. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (Per Protocol (PP) Population)
    Description RPQ/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-3 and RPQ-13 domain scores are presented separately. For each of the RPQ-3, RPQ-13, and RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain.
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed <20 sessions,1 because of illicit drug use during study.
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 35 32
    RPQ Total Score
    34.7
    (13.3)
    27.3
    (12.9)
    RPQ-3 Score
    5.8
    (2.9)
    4.5
    (2.5)
    RPQ-13 Score
    28.9
    (11.1)
    22.8
    (11.0)
    5. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (ITT Population)
    Description RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. The scores were derived by totaling the corresponding question scores for each domain and it's change from baseline.
    Time Frame Baseline to week 13, Months 6 and 12

    Outcome Measure Data

    Analysis Population Description
    1 subject in HBO2 missed the 6 month visit and 2 subjects missed the 12 month visit. 1 subject in the sham missed the week 13 visit and, 1 subject missed the month 6 visit and 3 subjects withdrew by month 12
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 36 35
    Week 13 change score
    -0.7
    (14.6)
    5.8
    (12.4)
    Month 6 change score
    -4.3
    (14.0)
    2.6
    (11.6)
    Month 12 change score
    5.7
    (14.7)
    5.5
    (12.4)
    6. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (ITT Population)
    Description RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. Analyses of the RPQ-3 domain scores are presented separately. For the RPQ-3 total scales, the scores were derived by totaling the corresponding question scores for each domain and it's change from baseline.
    Time Frame Baseline to week 13, Months 6 and 12

    Outcome Measure Data

    Analysis Population Description
    1 subject in HBO2 missed the 6 month visit and 2 subjects missed the 12 month visit. 1 subject in the sham missed the week 13 visit and, 1 subject missed the month 6 visit and 3 subjects withdrew by month 12
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 36 35
    Week 13 change score
    -0.3
    (2.7)
    1.2
    (2.2)
    Month 6 change score
    -1.4
    (2.7)
    0.3
    (2.2)
    Month 12 change score
    0.5
    (2.9)
    0.5
    (2.6)
    7. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (ITT Population)
    Description RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. For RPQ-13 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.
    Time Frame Baseline to week 13, Months 6 and 12

    Outcome Measure Data

    Analysis Population Description
    1 subject in HBO2 missed the 6 month visit and 2 subjects missed the 12 month visit. 1 subject in the sham missed the week 13 visit and, 1 subject missed the month 6 visit and 3 subjects withdrew by month 12
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 36 35
    Week 13 change score
    -0.4
    (12.3)
    4.7
    (11.1)
    Month 6 change score
    -3.0
    (11.9)
    2.3
    (9.9)
    Month 12 change score
    5.2
    (12.7)
    5.0
    (10.4)
    8. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population)
    Description RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. For the RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.
    Time Frame Baseline to week 13, Months 6 and 12

    Outcome Measure Data

    Analysis Population Description
    PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed <20 sessions,1 because of illicit drug use during study.
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 35 32
    Week 13 change score
    -1.0
    (14.7)
    6.1
    (12.6)
    Month 6 change score
    -4.3
    (14.0)
    3.2
    (11.3)
    Month 12 change score
    5.8
    (14.9)
    5.5
    (12.6)
    9. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population)
    Description RPQ/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. For the RPQ-3total scale, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.
    Time Frame Baseline to week 13, Months 6 and 12

    Outcome Measure Data

    Analysis Population Description
    PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed <20 sessions,1 because of illicit drug use during study.
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 35 32
    Week 13 change score
    -0.4
    (2.8)
    1.2
    (2.3)
    Month 6 change score
    -1.4
    (2.7)
    0.3
    (2.2)
    Month 12 change score
    0.4
    (2.9)
    0.5
    (2.7)
    10. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population)
    Description RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. The scores were derived by totaling the corresponding question scores for each domain and change from baseline.
    Time Frame Baseline to week 13, Months 6 and 12

    Outcome Measure Data

    Analysis Population Description
    PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed <20 sessions,1 because of illicit drug use during study.
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 35 32
    Week 13 change score
    -0.7
    (12.4)
    4.9
    (11.2)
    Month 6 change score
    -3.0
    (11.9)
    2.9
    (9.5)
    Month 12 change score
    5.4
    (12.8)
    5.1
    (10.6)
    11. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline: 24 and 36 Months (ITT Population)
    Description RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. For the RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.
    Time Frame Baseline to 24 months and 36 months

    Outcome Measure Data

    Analysis Population Description
    HBO2: 25 subs consented to 24 and 36 month f/u; 23 subs completed month 24 and 9 completed month 36; 2 subs missed 24 month visit. Sham: 17 subs consented to 24 and 36 month f/u. 17 completed month 24 and 5 completed month 36
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 36 35
    Baseline to 24 months
    1.2
    (18.5)
    2.9
    (11.9)
    Baseline to 36 months
    1.4
    (9.0)
    4.6
    (19.6)
    12. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline: 24 and 36 Months (ITT Population)
    Description RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. Analyses of the RPQ-3 domain scores are presented separately. For the RPQ-3 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.
    Time Frame Baseline to 24 months and 36 months

    Outcome Measure Data

    Analysis Population Description
    HBO2: 25 subs consented to 24 and 36 month f/u; 23 subs completed month 24 and 9 completed month 36; 2 subs missed 24 month visit. Sham: 17 subs consented to 24 and 36 month f/u. 17 completed month 24 and 5 completed month 36
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 36 35
    Baseline to 24 months
    -0.2
    (3.2)
    -0.1
    (2.7)
    Baseline to 36 months
    -0.9
    (2.9)
    0.8
    (3.0)
    13. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline: 24 and 36 Months (ITT Population)
    Description RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. For RPQ-13 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.
    Time Frame Baseline to 24 months and 36 months

    Outcome Measure Data

    Analysis Population Description
    HBO2: 25 subs consented to 24 and 36 month f/u; 23 subs completed month 24 and 9 completed month 36; 2 subs missed 24 month visit. Sham: 17 subs consented to 24 and 36 month f/u. 17 completed month 24 and 5 completed month 36
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 36 35
    Baseline to 24 months
    1.4
    (16.1)
    3.0
    (9.5)
    Baseline to 36 months
    2.0
    (7.5)
    3.8
    (16.8)
    14. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population)
    Description RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. For the RPQ total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.
    Time Frame Baseline to month 24 and month 36

    Outcome Measure Data

    Analysis Population Description
    PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed <20 sessions,1 because of illicit drug use during study.
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 35 32
    Baseline to month 24
    1.2
    (18.5)
    2.9
    (11.9)
    Baseline to month 36
    1.4
    (9.0)
    4.6
    (19.6)
    15. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population)
    Description RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-3 ranges from 0-12 and access a subset of symptoms. Analyses of the RPQ-3 domain scores are presented separately. For the RPQ-3 total scales, the scores were derived by totaling the corresponding question scores for each domain and change from baseline.
    Time Frame Baseline to month 24 and month 36

    Outcome Measure Data

    Analysis Population Description
    PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed <20 sessions,1 because of illicit drug use during study.
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 35 32
    Baseline to month 24
    -0.2
    (3.2)
    -0.1
    (2.7)
    Baseline to month 36
    -0.9
    (2.9)
    0.8
    (3.0)
    16. Secondary Outcome
    Title Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population)
    Description RPQ was created to measure the severity of post-concussion symptoms following traumatic brain injury. 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 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. The RPQ scale includes 16 common post-concussion symptom items whose responses range from "0= Not experienced at" to "4= A severe problem". Total range is 0 to 64. RPQ-13 ranges from 0-52 and access's 13 remaining symptoms. Analyses of the RPQ-13 domain scores are presented separately. For RPQ-13 total scales, the scores were derived by totaling the corresponding question scores for each domain change from baseline.
    Time Frame Baseline to month 24 and month 36

    Outcome Measure Data

    Analysis Population Description
    PP was defined as subs who completed 20 chamber sessions and week13 f/u. PP was also restricted to subs who didn't report illicit drug use following randomization. 67 subs satisfied the PP, 35/36 HBO2 and 32/35 sham. 4 were excluded from the PP population, 3 excluded because they completed <20 sessions,1 because of illicit drug use during study.
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    Measure Participants 35 32
    Baseline to month 24
    1.4
    (16.1)
    3.0
    (9.5)
    Baseline to month 36
    2.0
    (7.5)
    3.8
    (16.8)

    Adverse Events

    Time Frame Safety was evaluated in-person during the first 3 months and at month 6, and via telephone follow-up calls at months 4, 5, and 7-12. Extended annual follow-up continued for up to 36 months through January 2016.
    Adverse Event Reporting Description
    Arm/Group Title HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Arm/Group Description Hyperbaric oxygen (HBO2) at 1.5 atms. Stratified by site and time from injury (less than one year versus one year or more), in which participants are randomized. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Hyperbaric oxygen (HBO2) at 1.5 atms: The Hyperbaric oxygen (HBO2) at 1.5 atms (active) group (hyperbaric oxygen-chamber compressed to 1.5 atm abs and breathing 100% oxygen). Each participant should complete 40 sessions over the course of 12 weeks, one session per day, five per week. Sham control 1.2 atms. Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs). Sham control 1.2 atms: The chamber will be compressed with air to 1.2 atm abs to simulate the active group. Participants will don a hood and breathe 21% oxygen (room air). Each participant will complete 40 sessions, one session per day, five sessions per week, within 12 weeks following randomization. Breathing air at a pressure of 1.2 atm abs is equivalent to inhaling 25% oxygen at sea level pressure (1.0 atm abs).
    All Cause Mortality
    HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/36 (0%) 0/35 (0%)
    Serious Adverse Events
    HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/36 (13.9%) 3/35 (8.6%)
    General disorders
    Pain 1/36 (2.8%) 1 0/35 (0%) 0
    Infections and infestations
    Cellulitis 0/36 (0%) 0 1/35 (2.9%) 1
    Injury, poisoning and procedural complications
    Fall 1/36 (2.8%) 1 0/35 (0%) 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 1/36 (2.8%) 1 0/35 (0%) 0
    Psychiatric disorders
    Post-traumatic stress disorder 2/36 (5.6%) 2 0/35 (0%) 0
    Psychotic disorder 0/36 (0%) 0 1/35 (2.9%) 1
    Suicide attempt 0/36 (0%) 0 1/35 (2.9%) 1
    Other (Not Including Serious) Adverse Events
    HBO2 at 1.5 Atomspheres Absolute (ATA) Sham Control (1.2 Atomspheres)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 35/36 (97.2%) 34/35 (97.1%)
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders 1/36 (2.8%) 1 0/35 (0%) 0
    Congenital, familial and genetic disorders
    Congenital, familial and genetic disorders 1/36 (2.8%) 1 0/35 (0%) 0
    Ear and labyrinth disorders
    Vertigo 3/36 (8.3%) 5 3/35 (8.6%) 3
    Endocrine disorders
    Endocrine disorders 1/36 (2.8%) 1 0/35 (0%) 0
    Eye disorders
    Eye disorders 11/36 (30.6%) 14 7/35 (20%) 10
    Gastrointestinal disorders
    Nausea 4/36 (11.1%) 5 1/35 (2.9%) 2
    Hepatobiliary disorders
    Hepatobiliary disorders 1/36 (2.8%) 1 0/35 (0%) 0
    Immune system disorders
    Immune system disorders 1/36 (2.8%) 1 1/35 (2.9%) 1
    Infections and infestations
    Upper respiratory tract infection 16/36 (44.4%) 18 10/35 (28.6%) 13
    Gastroenteritis 1/36 (2.8%) 1 6/35 (17.1%) 7
    Sinusitis 4/36 (11.1%) 4 4/35 (11.4%) 4
    Nasopharyngitis 4/36 (11.1%) 4 3/35 (8.6%) 3
    Injury, poisoning and procedural complications
    Barotitis media 13/36 (36.1%) 20 6/35 (17.1%) 8
    Sinus barotrauma 5/36 (13.9%) 10 4/35 (11.4%) 9
    Contusion 6/36 (16.7%) 8 3/35 (8.6%) 3
    Ligament sprain 0/36 (0%) 0 5/35 (14.3%) 5
    Mucsle strain 1/36 (2.8%) 1 3/35 (8.6%) 3
    Investigations
    Investigations 5/36 (13.9%) 7 3/35 (8.6%) 4
    Metabolism and nutrition disorders
    Vitamin D deficiency 3/36 (8.3%) 3 1/35 (2.9%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 3/36 (8.3%) 5 3/35 (8.6%) 6
    Arthralgia 4/36 (11.1%) 5 2/35 (5.7%) 3
    Neck pain 0/36 (0%) 0 4/35 (11.4%) 4
    Tendonitis 1/36 (2.8%) 1 3/35 (8.6%) 3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified 0/36 (0%) 0 1/35 (2.9%) 1
    Nervous system disorders
    Dizziness 6/36 (16.7%) 7 1/35 (2.9%) 2
    Headache 4/36 (11.1%) 4 2/35 (5.7%) 3
    Psychiatric disorders
    Suicidal ideation 2/36 (5.6%) 2 2/35 (5.7%) 2
    Renal and urinary disorders
    Renal and urinary disorders 3/36 (8.3%) 4 0/35 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion 5/36 (13.9%) 5 4/35 (11.4%) 5
    Dyspnea 4/36 (11.1%) 4 1/35 (2.9%) 1
    Epistaxis 2/36 (5.6%) 2 2/35 (5.7%) 2
    Sinus congestion 2/36 (5.6%) 2 2/35 (5.7%) 2
    Skin and subcutaneous tissue disorders
    Rash 1/36 (2.8%) 2 3/35 (8.6%) 3
    General disorders and administration site conditions 6/36 (16.7%) 6 1/35 (2.9%) 2
    Vascular disorders
    Vascular disorders 5/36 (13.9%) 6 0/35 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Lindell Weaver, MD, FACP, UHM
    Organization Intermountain Healthcare
    Phone 801-408-3623
    Email lindell.weaver@imail.org
    Responsible Party:
    U.S. Army Medical Research and Development Command
    ClinicalTrials.gov Identifier:
    NCT01611194
    Other Study ID Numbers:
    • S-11-17
    First Posted:
    Jun 4, 2012
    Last Update Posted:
    Nov 21, 2018
    Last Verified:
    Oct 1, 2018