Traumatic Brain Injury With Brief Loss of ConsciousnessPhase 2BIMANCT01611194
mTBI Mechanisms of Action of HBO2 for Persistent Post-Concussive Symptoms
A Phase 2 study testing Hyperbaric oxygen (HBO2) at 1.5 atms in people with Traumatic Brain Injury With Brief Loss of Consciousness and Post-Concussion Syndrome, run by U.S. Army Medical Research and Development Command at 5 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Traumatic Brain Injury With Brief Loss of Consciousness, Post-Concussion Syndrome
- What is being tested?
- Hyperbaric oxygen (HBO2) at 1.5 atms
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 5 sitesUnited States
- Study dates
- 11 Sep 2012to 29 Jan 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Outcomes Assessment Center, Evans Army Community Hospital
Colorado Springs, Colorado, 80913
Evans Army Community Hospital / Hyperbaric Medicine Complex
Fort Carson, Colorado, 80913
Joint Base Lewis-McChord
Fort Lewis, Washington, 98438
Camp Lejeune
Jacksonville, North Carolina, 28542
TBI Program/HBO2 Research Program Madigan Healthcare system
Tacoma, Washington, 98431
About this study
Official title: Brain Injury and Mechanisms of Action of HBO2 for Persistent Post-Concussive Symptoms After Mild Traumatic Brain Injury (BIMA) Protocol
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
Read the 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.
- Being tested
- Hyperbaric oxygen (HBO2) at 1.5 atms, Sham control 1.2 atms
- Keywords
- HBO2, HBOT, mTBI, Brain injury, PCS, PTSD, hyperbaric oxygen
- Medical subject headings
- Post-Concussion Syndrome, Brain Injuries, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperbaric oxygen (HBO2) at 1.5 atmsDrug
Also called 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 atmsDrug
Also called 1.2 atms (shame)
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).
| Study group | Role | What they receive |
|---|---|---|
| HBO2 at 1.5 Atomspheres Absolute (ATA) | Experimental | 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. Receives: Drug: Hyperbaric oxygen (HBO2) at 1.5 atms |
| Sham Control (1.2 Atomspheres) | Sham comparator | 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). Receives: Drug: Sham control 1.2 atms |
What is being measured
The primary outcome is the main question the study is designed to answer.
Summary of Treatment-Emergent Adverse Events
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.
Measured: months 3, 6, 4, 5 and 7-12. Extended f/u up to 36 months
Summary of Study Intervention-Related Adverse Events
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.
Measured: months 3, 6, 4, 5 and 7-12. Extended f/u up to 36 months
Secondary outcomes (14)
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (ITT Population)
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.
Measured: Baseline
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)
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.
Measured: Baseline
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (ITT Population)
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.
Measured: Baseline to week 13, Months 6 and 12
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (ITT Population)
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.
Measured: Baseline to week 13, Months 6 and 12
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (ITT Population)
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.
Measured: Baseline to week 13, Months 6 and 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)
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.
Measured: Baseline to week 13, Months 6 and 12
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population)
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.
Measured: Baseline to week 13, Months 6 and 12
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population)
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.
Measured: Baseline to week 13, Months 6 and 12
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)
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.
Measured: Baseline to 24 months and 36 months
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)
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.
Measured: Baseline to 24 months and 36 months
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)
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.
Measured: Baseline to 24 months and 36 months
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population)
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.
Measured: Baseline to month 24 and month 36
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population)
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.
Measured: Baseline to month 24 and month 36
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population)
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.
Measured: Baseline to month 24 and month 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2012 (estimated)
- Study start11 Sep 2012
- Primary completionJan 2015
- Study completion29 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain Injury With Brief Loss of ConsciousnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Lindell Weaver, MD, Principal investigator, Intermountain Health Care, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01611194
- Sponsor's protocol ID
- S-11-17
- Acronym
- BIMA
- Status last verified
- Oct 2018
- First submitted
- 3 May 2012
- Last updated
- 21 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Weaver LK, Churchill S, Wilson SH, Hebert D, Deru K, Lindblad AS. A composite outcome for mild traumatic brain injury in trials of hyperbaric oxygen. Undersea Hyperb Med. 2019 BIMA Special Edition No. Feb;46(3):341-352.
PubMed 31394603Churchill S, Deru K, Weaver LK, Wilson SH, Hebert D, Miller RS, Lindblad AS. Adverse events and blinding in two randomized trials of hyperbaric oxygen for persistent post-concussive symptoms. Undersea Hyperb Med. 2019 BIMA Special Edition No. Feb;46(3):331-340.
PubMed 31394602Hart BB, Wilson SH, Churchill S, Deru K, Weaver LK, Minnakanti M, Lindblad AS. Extended follow-up in a randomized trial of hyperbaric oxygen for persistent post-concussive symptoms. Undersea Hyperb Med. 2019 BIMA Special Edition No. Feb;46(3):313-327.
PubMed 31394601Wetzel PA, Lindblad AS, Mulatya C, Kannan MA, Villmar Z, Gitchel GT, Weaver LK. Eye tracker outcomes in a randomized trial of 40 sessions of hyperbaric oxygen or sham in participants with persistent post concussive symptoms. Undersea Hyperb Med. 2019 BIMA Special Edition No. Feb;46(3):299-311.
PubMed 31394600Walker JM, Mulatya C, Hebert D, Wilson SH, Lindblad AS, Weaver LK. Sleep assessment in a randomized trial of hyperbaric oxygen in U.S. service members with post concussive mild traumatic brain injury compared to normal controls. Sleep Med. 2018 Nov;51:66-79. doi: 10.1016/j.sleep.2018.06.006. Epub 2018 Jun 30.
PubMed 30099354Wetzel PA, Lindblad AS, Raizada H, James N, Mulatya C, Kannan MA, Villamar Z, Gitchel GT, Weaver LK. Eye Tracking Results in Postconcussive Syndrome Versus Normative Participants. Invest Ophthalmol Vis Sci. 2018 Aug 1;59(10):4011-4019. doi: 10.1167/iovs.18-23815.
PubMed 30098189Meehan A, Searing E, Weaver LK, Lewandowski A. Baseline vestibular and auditory findings in a trial of post-concussive syndrome. Undersea Hyperb Med. 2016 Aug-Sept;43(5):567-584.
PubMed 28771392Wilson SH, Weaver LK, Lindblad AS. Neuropsychological assessments in a hyperbaric trial of post-concussive symptoms. Undersea Hyperb Med. 2016 Aug-Sept;43(5):585-599.
PubMed 28768075Walker JM, James NT, Campbell H, Wilson SH, Churchill S, Weaver LK. Sleep assessments for a mild traumatic brain injury trial in a military population. Undersea Hyperb Med. 2016 Aug-Sept;43(5):549-566.
PubMed 28768073Mirow S, Wilson SH, Weaver LK, Churchill S, Deru K, Lindblad AS. Linear analysis of heart rate variability in post-concussive syndrome. Undersea Hyperb Med. 2016 Aug-Sept;43(5):531-547.
PubMed 28768072Williams CS, Spitz MC, Foley JF, Weaver LK, Lindblad AS, Wierzbicki MR. Baseline EEG abnormalities in mild traumatic brain injury from the BIMA study. Undersea Hyperb Med. 2016 Aug-Sept;43(5):521-530.
PubMed 28768071Williams CS, Weaver LK, Lindblad AS, Kumar S, Langford DR. Baseline neurological evaluations in a hyperbaric trial of post-concussive syndrome. Undersea Hyperb Med. 2016 Aug-Sept;43(5):511-519.
PubMed 28768070Weaver LK, Chhoeu A, Lindblad AS, Churchill S, Wilson SH. Hyperbaric oxygen for mild traumatic brain injury: Design and baseline summary. Undersea Hyperb Med. 2016 Aug-Sept;43(5):491-509.
PubMed 28768069
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Injury and Mechanisms of Action of HBO2 for Persistent Post-Concussive Symptoms After Mild Traumatic Brain Injury (BIMA) Protocol
- ClinicalTrials.gov ID
- NCT01611194
- Acronym / sponsor ID
- BIMA / S-11-17
- Keywords
- HBO2, HBOT, mTBI, Brain injury, PCS, PTSD, hyperbaric oxygen
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Study start
- 11 Sep 2012 (actual)
- Primary completion
- Jan 2015 (actual)
- Study completion
- 29 Jan 2016 (actual)
- First posted
- 4 Jun 2012 (estimated)
- Results
- Posted 21 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HBO2 at 1.5 Atomspheres Absolute (ATA) | Experimental | Drug: Hyperbaric oxygen (HBO2) at 1.5 atmsHyperbaric 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. |
| Sham Control (1.2 Atomspheres) | Sham comparator | Drug: Sham control 1.2 atmsSham 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). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (58 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperbaric oxygen (HBO2) at 1.5 atmsAlso: 1.5 atmsThe 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. | Drug | HBO2 at 1.5 Atomspheres Absolute (ATA) |
| Sham control 1.2 atmsAlso: 1.2 atms (shame)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). | Drug | Sham Control (1.2 Atomspheres) |
Primary outcome
Summary of Treatment-Emergent Adverse Events
Time frame: 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.
Summary of Study Intervention-Related Adverse Events
Time frame: 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.
14 secondary outcomes
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ, RPQ3 and RPQ13) - Baseline (ITT Population)
Time frame: Baseline
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)
Time frame: Baseline
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (ITT Population)
Time frame: Baseline to week 13, Months 6 and 12
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (ITT Population)
Time frame: Baseline to week 13, Months 6 and 12
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (ITT Population)
Time frame: Baseline to week 13, Months 6 and 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)
Time frame: Baseline to week 13, Months 6 and 12
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population)
Time frame: Baseline to week 13, Months 6 and 12
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population)
Time frame: Baseline to week 13, Months 6 and 12
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)
Time frame: Baseline to 24 months and 36 months
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)
Time frame: Baseline to 24 months and 36 months
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)
Time frame: Baseline to 24 months and 36 months
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ) - Change From Baseline (Per Protocol (PP) Population)
Time frame: Baseline to month 24 and month 36
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ3) - Change From Baseline (Per Protocol (PP) Population)
Time frame: Baseline to month 24 and month 36
Presence of Post Concussion Symptoms Following Traumatic Brain Injury Using The Rivermead Post-Concussion Symptom Questionnaire (RPQ13) - Change From Baseline (Per Protocol (PP) Population)
Time frame: Baseline to month 24 and month 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31394603Weaver LK, Churchill S, Wilson SH, Hebert D, Deru K, Lindblad AS. A composite outcome for mild traumatic brain injury in trials of hyperbaric oxygen. Undersea Hyperb Med. 2019 BIMA Special Edition No. Feb;46(3):341-352.
- Derived from this study: PubMed 31394602Churchill S, Deru K, Weaver LK, Wilson SH, Hebert D, Miller RS, Lindblad AS. Adverse events and blinding in two randomized trials of hyperbaric oxygen for persistent post-concussive symptoms. Undersea Hyperb Med. 2019 BIMA Special Edition No. Feb;46(3):331-340.
- Derived from this study: PubMed 31394601Hart BB, Wilson SH, Churchill S, Deru K, Weaver LK, Minnakanti M, Lindblad AS. Extended follow-up in a randomized trial of hyperbaric oxygen for persistent post-concussive symptoms. Undersea Hyperb Med. 2019 BIMA Special Edition No. Feb;46(3):313-327.
- Derived from this study: PubMed 31394600Wetzel PA, Lindblad AS, Mulatya C, Kannan MA, Villmar Z, Gitchel GT, Weaver LK. Eye tracker outcomes in a randomized trial of 40 sessions of hyperbaric oxygen or sham in participants with persistent post concussive symptoms. Undersea Hyperb Med. 2019 BIMA Special Edition No. Feb;46(3):299-311.
- Derived from this study: PubMed 30099354Walker JM, Mulatya C, Hebert D, Wilson SH, Lindblad AS, Weaver LK. Sleep assessment in a randomized trial of hyperbaric oxygen in U.S. service members with post concussive mild traumatic brain injury compared to normal controls. Sleep Med. 2018 Nov;51:66-79. doi: 10.1016/j.sleep.2018.06.006. Epub 2018 Jun 30.
- Derived from this study: PubMed 30098189Wetzel PA, Lindblad AS, Raizada H, James N, Mulatya C, Kannan MA, Villamar Z, Gitchel GT, Weaver LK. Eye Tracking Results in Postconcussive Syndrome Versus Normative Participants. Invest Ophthalmol Vis Sci. 2018 Aug 1;59(10):4011-4019. doi: 10.1167/iovs.18-23815.
- Derived from this study: PubMed 28771392Meehan A, Searing E, Weaver LK, Lewandowski A. Baseline vestibular and auditory findings in a trial of post-concussive syndrome. Undersea Hyperb Med. 2016 Aug-Sept;43(5):567-584.
- Derived from this study: PubMed 28768075Wilson SH, Weaver LK, Lindblad AS. Neuropsychological assessments in a hyperbaric trial of post-concussive symptoms. Undersea Hyperb Med. 2016 Aug-Sept;43(5):585-599.
- Derived from this study: PubMed 28768073Walker JM, James NT, Campbell H, Wilson SH, Churchill S, Weaver LK. Sleep assessments for a mild traumatic brain injury trial in a military population. Undersea Hyperb Med. 2016 Aug-Sept;43(5):549-566.
- Derived from this study: PubMed 28768072Mirow S, Wilson SH, Weaver LK, Churchill S, Deru K, Lindblad AS. Linear analysis of heart rate variability in post-concussive syndrome. Undersea Hyperb Med. 2016 Aug-Sept;43(5):531-547.
- Derived from this study: PubMed 28768071Williams CS, Spitz MC, Foley JF, Weaver LK, Lindblad AS, Wierzbicki MR. Baseline EEG abnormalities in mild traumatic brain injury from the BIMA study. Undersea Hyperb Med. 2016 Aug-Sept;43(5):521-530.
- Derived from this study: PubMed 28768070Williams CS, Weaver LK, Lindblad AS, Kumar S, Langford DR. Baseline neurological evaluations in a hyperbaric trial of post-concussive syndrome. Undersea Hyperb Med. 2016 Aug-Sept;43(5):511-519.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lindell Weaver, MD principal investigator
Intermountain Health Care, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hyperbaric oxygen (HBO2) at 1.5 atms in people with Traumatic Brain Injury With Brief Loss of Consciousness and Post-Concussion Syndrome, run by U.S. Army Medical Research and Development Command at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 58 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Summary of Treatment-Emergent Adverse Events (time frame: months 3, 6, 4, 5 and 7-12. Extended f/u up to 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01611194, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2018.