Hyperbaric Oxygen Therapy (HBO2) for Persistent Post-concussive Symptoms After Mild Traumatic Brain Injury (mTBI)

NCT01306968 | Completed Phase 2 Results

• 1 other identifier: S-10-09
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase II randomized trial designed to describe the magnitude of change between baseline and follow-up outcomes for symptom surveys and a battery of neuropsychological tests administered at time points corresponding before and after 10 weeks over observation in four groups:

• A military population with post-concussion syndrome (mTBI) receiving local standard care
• A military population with post-concussion syndrome (mTBI) receiving local standard care and sham hyperbaric oxygen sessions
• A military population with post-concussion syndrome (mTBI) receiving local standard care and hyperbaric oxygen at 1.5 atmospheres sessions
• A otherwise similar group with PTSD but no history of TBI receiving local standard care Differences and variability of the tests will be used for determining the optimum primary endpoint(s) for future trial, as well as for refinement of sample size and power calculations for these studies. The groups undergoing hyperbaric sessions will be assigned to receive HBO2 or sham using a randomized, double blind design. Active duty military (Army, Marine, Navy, Air Force) men and non-pregnant women residing in the United States and who will remain in the military for the entire study period, aged 18-65 years who have been deployed one or more times to the US Central Command since the initiation of Operation Enduring Freedom (October 7, 2001) who either:
• have been diagnosed with Post Traumatic Stress Disorder (PTSD) as a result of traumatic events that occurred during the qualifying CENTCOM deployment, but have no diagnosed or suspected lifetime brain injuries resulting in loss or alteration of consciousness; OR
• have been diagnosed with at least one mild brain injury (mTBI) with persistent (\> 4 months) symptoms sustained during one or more of those deployments

Conditions

Post-concussive Symptoms; Traumatic Brain Injury

Keywords

mild tramatic brain injury; mTBI; hyperbaric oxygen; post concussive symptoms; active duty military; veterans

Outcome Measures

Primary Outcomes (4)

• Post-Intervation Post-concussion Symptom Scores Using RPQ - Intent to Treat

  The Rivermead Post-Concussion Symptom Questionnaire (RPQ)/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. The 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 outcome 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.

  Follow-up Visit 2; Day 56 (up to day 100) for groups not recieving HBO2, Day 70 for groups recieving HBO2

• Change in Post-concussion Symptom Scores Using RPQ - Intent to Treat

  Means for the change from baseline to follow-up visit 2

  Follow-up Visit 2; Day 56 (up to day 100) for groups not recieving HBO2, Day 70 for groups recieving HBO2

• Post-Intervation Post-concussion Symptom Scores Using RPQ - Per Protocol Population

  The Rivermead Post-Concussion Symptom Questionnaire (RPQ)/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. The 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 outcome 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.

  Follow-up Visit 2; Day 56 (up to day 100) for groups not recieving HBO2, Day 70 for groups recieving HBO2

• Change in Post-concussion Symptom Scores Using RPQ - Per Protocol Population

  The Rivermead Post-Concussion Symptom Questionnaire (RPQ)/RPQ-3 was created to measure the severity of post-concussion symptoms following traumatic brain injury. The 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 outcome 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.

  Follow-up Visit 2; Day 56 (up to day 100) for groups not recieving HBO2, Day 70 for groups recieving HBO2

Study Arms (4)

Standard TBI Care

NO INTERVENTION

Routine post-concussive symptoms (PCS) care as practiced within Departments of Defense (DoD)

HBO2 Group

EXPERIMENTAL

Routine PCS care supplemented with hyperbaric oxygen (HBO2) at the dose of 1.5 ATA for 60 minutes administered over 40 sessions given daily Monday through Friday

Drug: hyperbaric oxygen

Sham Group

SHAM COMPARATOR

Routine PCS care supplemented with an otherwise identical sham hyperbaric air exposure at 1.2 atmospheres absolute (ATA)

Other: sham hyperbaric air

PTSD With no History of TBI

NO INTERVENTION

Subjects who have been diagnosed with PTSD but have no diagnosed or suspected brain injuries. This group does not receive HBO2.

Interventions

hyperbaric oxygen DRUG

The chamber will be compressed with air to 1.5 atm abs. Once the chamber is compressed to 1.5 atm abs, the subjects will don a hood and breathe 100% oxygen. Hoods will be supplied with oxygen with flows of at least 30 liters per minute and overboard dumping of excess gas. Each subject will complete 40 sessions. The duration of the hyperbaric oxygen exposures will be 60 minutes (±2 minutes), timed from when the chamber hatch or door closes, and ending when the chamber hatch or door opens ("door-to-door" time equals 60 minutes). The total intervention exposure time is 50 minutes (±2 minutes). The interval to compress to the intervention pressure (1.5 atm abs) and will be 5 minutes (±1 minute). The interval to decompress from the study pressure will be 5 minutes (±1 minute).

Also known as: medical oxygen

HBO2 Group

sham hyperbaric air OTHER

A pressure of 1.2 atm abs will provide an equivalent inhaled oxygen concentration of 25%. The duration of the sham exposures will be 60 minutes (±2 minutes). Each subject will complete 40 sessions.

Sham Group

Eligibility Criteria

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

You may qualify if:

• Volunteers must have history of at least one mild traumatic brain injury (mTBI) with persistent symptoms that meets all the following criteria:
• Brain injury that occurred more than 4 months prior to enrollment, with the most recent injury occurring no earlier than October 7, 2001.
• Most recent traumatic brain injury occurred while serving on active duty, and while deployed to the United States (US) Central Command (USCENTCOM).
• Most recent traumatic brain injury was caused by blast exposure or blunt trauma.
• Most recent traumatic brain injury resulted in at least one of the following: 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).
• Volunteers must also meet all the following criteria:
• years old at the time of study enrollment.
• A TRICARE beneficiary at the time of consent and during study participation.
• Has current complaints of brain injury symptoms such as headache, dizziness, or cognitive or affective problems that score at least 3 post-concussive symptoms as assessed by the Ohio State University (OSU) Traumatic Brain Injury (TBI) Identification (ID) Method interview
• Has received current local care pharmacologic and non-pharmacologic interventions for TBI and any concomitant posttraumatic stress disorder (PTSD) with no significant change in therapy for at least 1 month
• Willing and committed to comply with the research protocol and complete all outcome measures.
• Able to self-consent.
• Able to speak and read English, as primary language.
• Able to participate in all outcome measures.
• Able to equalize middle ear pressure.

You may not qualify if:

• History of brain injury of moderate or severe degree: duration of loss of consciousness at the time of injury greater than 30 minutes, or duration of post-traumatic amnesia greater than 24 hours, or brain injury of a penetrating etiology.
• History of brain injury not of traumatic etiology, such as stroke or drug-induced coma.
• Prior treatment with HBO2.
• Hyperbaric chamber inside attendant, professional (paid)underwater diver (commercial, operational/ military, instructor), or technical diver.
• Pregnancy, women who plan to become pregnant during the study period, women who do not agree to practice an acceptable form of birth control during the study period, or women who are breastfeeding;
• Those who are unable to participate fully in outcome assessments (Blind in one or both eyes; Deaf in one or both ears; or Ambulation with assistive devices
• Pre-existing diagnosis of a psychotic disorder(s): schizophrenia, dissociative disorder, and bipolar disease.
• Verifiable degenerative mental disease (e.g., Alzheimer's disease, multiple sclerosis, senile dementia).
• Epilepsy or seizure disorder requiring anticonvulsants.
• Active malignancy, prior malignancy (except basal cell carcinoma) within the last 5 years.
• Presence of chronic debilitating disease (e.g., end-stage renal disease, end-stage liver disease, all types of diabetes with or without sequelae).
• Documented clinically significant uncorrected anemia
• Documented sickle cell disease.
• History of therapeutic ionizing radiation to the head.
• Verifiable diagnosis of learning disability.

Sponsors & Collaborators

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

Study Sites (5)

Naval Hospital Camp Pendleton

Camp Pendleton, California, 92055, United States

Location

Evans Army community Hospital Fort Carson

Fort Carson, Colorado, 80913, United States

Location

Eisenhower Army Medical Center

Fort Gordon, Georgia, 30905, United States

Location

Naval Hospital Camp Lejeune

Marine Corps Base Camp Lejeune, North Carolina, 28547, United States

Location

Study Coordinating Center, LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

Related Publications (3)

• 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

• Miller RS, Weaver LK, Bahraini N, Churchill S, Price RC, Skiba V, Caviness J, Mooney S, Hetzell B, Liu J, Deru K, Ricciardi R, Fracisco S, Close NC, Surrett GW, Bartos C, Ryan M, Brenner LA; HOPPS Trial Team. Effects of hyperbaric oxygen on symptoms and quality of life among service members with persistent postconcussion symptoms: a randomized clinical trial. JAMA Intern Med. 2015 Jan;175(1):43-52. doi: 10.1001/jamainternmed.2014.5479.

  PMID: 25401463 DERIVED

MeSH Terms

Conditions

Post-Concussion Syndrome; Brain Injuries, Traumatic

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Brain Concussion; Head Injuries, Closed; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating; Brain Injuries; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Oxygen Inhalation Therapy; Respiratory Therapy; Therapeutics

Results Point of Contact

• Title: Dr. R. Scott Miller, M.D.
• Organization: Uniformed Services University of Health Sciences

robert.s.miller@us.army.mil

301-816-8424

Study Officials

• Scott Miller, MD, COL

  United States Army Medical Materiel Development Activity

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2011
• First Posted: March 2, 2011
• Study Start: February 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: September 5, 2014
• Results First Posted: September 5, 2014

Record last verified: 2014-08

Locations

US (5)