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

NCT01611194 | Completed Phase 2 Results

• 1 other identifier: S-11-17
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 5

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

Conditions

Traumatic Brain Injury With Brief Loss of Consciousness; Post-Concussion Syndrome

Keywords

HBO2; HBOT; mTBI; Brain injury; PCS; PTSD; hyperbaric oxygen

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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)

  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)

  Baseline

• 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

• 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

• 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

Study Arms (2)

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.

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).

Drug: Sham control 1.2 atms

Interventions

Hyperbaric oxygen (HBO2) at 1.5 atms DRUG

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.

Also known as: 1.5 atms

HBO2 at 1.5 Atomspheres Absolute (ATA)

Sham control 1.2 atms DRUG

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).

Also known as: 1.2 atms (shame)

Sham Control (1.2 Atomspheres)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead

Study Sites (5)

Outcomes Assessment Center, Evans Army Community Hospital

Colorado Springs, Colorado, 80913, United States

Location

Evans Army Community Hospital / Hyperbaric Medicine Complex

Fort Carson, Colorado, 80913, United States

Location

Camp Lejeune

Jacksonville, North Carolina, 28542, United States

Location

Joint Base Lewis-McChord

Fort Lewis, Washington, 98438, United States

Location

TBI Program/HBO2 Research Program Madigan Healthcare system

Tacoma, Washington, 98431, United States

Location

Related Publications (13)

• 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.

  PMID: 31394603 DERIVED

• Churchill 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.

  PMID: 31394602 DERIVED

• Hart 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.

  PMID: 31394601 DERIVED

• Wetzel 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.

  PMID: 31394600 DERIVED

• Walker 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.

  PMID: 30099354 DERIVED

• Wetzel 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.

  PMID: 30098189 DERIVED

• Meehan 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.

  PMID: 28771392 DERIVED

• Wilson 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.

  PMID: 28768075 DERIVED

• Walker 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.

  PMID: 28768073 DERIVED

• Mirow 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.

  PMID: 28768072 DERIVED

• Williams 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.

  PMID: 28768071 DERIVED

• Williams 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.

  PMID: 28768070 DERIVED

• Weaver 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.

  PMID: 28768069 DERIVED

MeSH Terms

Conditions

Post-Concussion Syndrome; Brain Injuries; Stress Disorders, Post-Traumatic

Interventions

Oxyhemoglobins

Condition Hierarchy (Ancestors)

Brain Concussion; Head Injuries, Closed; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating; Brain Diseases; Central Nervous System Diseases; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Hemoglobins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globins; Hemeproteins

Results Point of Contact

• Title: Lindell Weaver, MD, FACP, UHM
• Organization: Intermountain Healthcare

lindell.weaver@imail.org

801-408-3623

Study Officials

• Lindell Weaver, MD

  Intermountain Health Care, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2012
• First Posted: June 4, 2012
• Study Start: September 11, 2012
• Primary Completion: January 1, 2015
• Study Completion: January 29, 2016
• Last Updated: November 21, 2018
• Results First Posted: November 21, 2018

Record last verified: 2018-10

Locations

US (5)