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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01611194
First received: May 3, 2012
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Traumatic Brain Injury With Brief Loss of Consciousness
Post-Concussion Syndrome
Drug: Hyperbaric oxygen (HBO2) at 1.5 atms
Drug: Sham control 1.2 atms
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Change from baseline at 13 weeks and 6 months of neuropsychiatric measures [ Time Frame: 12 months, 40 HBO2 sessions ] [ Designated as safety issue: No ]
    Additionally, this study will describe the brain function and anatomy of active duty personnel and veterans with PCS who are symptomatic at least 3 months but no more than 5 years after mild traumatic brain injury using a comprehensive battery of assessments, across time, in groups randomized to receive intervention (hyperbaric oxygen) or sham control, and explore potential associations between changes in function, anatomy, and participant reported outcomes.


Secondary Outcome Measures:
  • compare rates of change in neuropsychiatric measure between treatment and sham [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    • To evaluate safety of the proposed hyperbaric oxygen versus sham interventions
    • To identify practical issues in instituting assessments among participants with PCS and to address related logistical considerations prior to initiating the pivotal study.
    • To compare outcome assessment results to a normative population, without history of traumatic brain injury (TBI), comprehensively assessed in a similar fashion in a companion study.


Estimated Enrollment: 72
Study Start Date: September 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active group (HBO2)
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.
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.
Sham Comparator: Sham control
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).

Detailed Description:

Under an IND held by the Office of the Army Surgeon General (IND 104,678), this study (BIMA) will obtain pilot data that will complement results from another pilot study (HOPPS). Results from BIMA and HOPPS will be used to select primary and secondary endpoints for a subsequent phase III efficacy trial of hyperbaric oxygen versus sham control for the treatment of post concussive syndrome (PCS). Ideal endpoint candidates will have properties that suggest an association with a neurologic mechanism.

Additionally, this study will describe the brain function and anatomy of active duty personnel and veterans with PCS who are symptomatic at least 3 months but no more than 5 years after mild traumatic brain injury using a comprehensive battery of assessments, across time, in groups randomized to receive intervention (hyperbaric oxygen) or sham control, and explore potential associations between changes in function, anatomy, and participant reported outcomes.

Secondary:

  • To evaluate safety of the proposed hyperbaric oxygen and sham interventions
  • To identify practical issues in instituting assessments among participants with PCS and to address related logistical considerations prior to initiating the pivotal study.
  • To compare outcome assessment results to a normative population, without history of traumatic brain injury (TBI), comprehensively assessed in a similar fashion in a companion study.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01611194

Locations
United States, Colorado
Outcomes Assessment Center, Evans Army Community Hospital
Colorado Springs, Colorado, United States, 80913
Evans Army Community Hospital / Hyperbaric Medicine Complex
Ft Carson, Colorado, United States, 80913
United States, North Carolina
Camp Lejeune
Jacksonville, North Carolina, United States, 28542
United States, Washington
Joint Base Lewis-McChord
Fort Lewis, Washington, United States, 98438
TBI Program/HBO2 Research Program Madigan Healthcare system
Tacoma, Washington, United States, 98431
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Lindell Weaver, MD Intermountain Health Care, Inc.
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01611194     History of Changes
Other Study ID Numbers: S-11-17
Study First Received: May 3, 2012
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
HBO2
HBOT
mTBI
Brain injury
PCS
PTSD
hyperbaric oxygen

Additional relevant MeSH terms:
Unconsciousness
Brain Injuries
Post-Concussion Syndrome
Wounds and Injuries
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Brain Concussion
Head Injuries, Closed
Wounds, Nonpenetrating

ClinicalTrials.gov processed this record on August 26, 2014