Hyperbaric Oxygen Treatment for Veterans With Traumatic Brain Injury

NCT06581003 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: STUDY006819: HBOT for TBI
• Study Type: interventional
• Target: 420
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this blinded, adaptive, randomized, placebo-controlled clinical trial is to investigate the use of hyperbaric oxygen as a therapy to treat mild to moderate traumatic brain injury in Veterans and active military. The main questions it aims to answer are:

• Does Hyperbaric Oxygen Therapy (HBOT) reduce neurobehavioral symptoms? (Aim 1)
• How many HBOT sessions are needed to achieve a significant reduction in neurobehavioral symptoms? (Aim 2)
• Does HBOT reduce posttraumatic stress disorder (PTSD) symptoms? (Aim 3) Exploratory objectives will explore if there are changes in: 1.) cognitive functioning using neuropsychological tests and the National Institutes of Health (NIH) toolbox, 2.) inflammation biomarkers in blood, 3.) microbiome in stool samples, 4.) electroencephalogram (EEG), 5.) sleep characteristics, and 6.) fMRI. Research will compare HBOT therapy to a placebo condition to see if HBOT works to treat neurobehavioral symptoms. The placebo condition is a chamber that remains unpressurized and has 21% oxygen. Participants will:
• Complete baseline assessments to determine eligibility.
• Attend 40 sessions of HBOT or placebo (normal air) within 12 weeks.
• Complete questionnaires and interviews throughout the course of the study.
• Complete a 2-week post treatment visit

Conditions

Traumatic Brain Injury; Military Operations

Keywords

hyperbaric chamber; neuromodulation

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in the Neurobehavioral Symptoms at 2 weeks Post Intervention

  Measured by the Neurobehavioral Symptom Inventory (NSI). The severity of each symptom on the NSI is measured using a 5-item scale (0-none to 4-very severe) that asks patients to indicate the extent to which each symptom has disturbed them in the previous 2 weeks. The NSI total score is the sum of severity ratings of the 22 symptoms. Cluster scores (domains: physical, cognitive, affective, and sensory) were derived.

  at 2 weeks post treatment

Secondary Outcomes (1)

• Change from Baseline in post traumatic stress disorder symptoms at 2 weeks post intervention

  at 2 weeks post treatment

Study Arms (2)

HBOT Group

EXPERIMENTAL

HBOT chamber pressurized to 2.0 ATA with 100% oxygen

Drug: Oxygen 99.7 %

Placebo/Sham Group

SHAM COMPARATOR

HBOT chamber that remains unpressurized and has 21% oxygen

Drug: Oxygen 21 %

Interventions

Oxygen 99.7 % DRUG

The experimental group will undergo HBOT in a specialized chamber at a pressure of 2.0 ATA. Oxygen will be delivered at 100% for 60 minutes.

HBOT Group

Oxygen 21 % DRUG

The control group will be placed in the same specialized chamber, but pressure will be 1.0 ATA (normobaric), and oxygen will be delivered at 21% (normal oxygen concentration in room air) for 60 minutes.

Placebo/Sham Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• U.S. Service Members and Veterans, between 18 and 75 years of age
• Ability to read, write, and speak English.
• Ability to provide informed consent.
• History of TBI. Participants must have a minimum of 1 year post injury and a TBI classified as mild to moderate as determined by with the Ohio State University TBI Identification Method (Bogner, 2009).
• Experiencing chronic symptoms of TBI as determined by at least a NSI total score of ≥22 (based on previous work using this score; Harch et al., 2020.
• Able to tolerate the HBOT environment lying down for one hour.

You may not qualify if:

• Received HBOT within the last 3 months.
• Concurrently enrolled in another clinical trial.
• Pregnancy or plans to become pregnant during the study period.
• Lactating
• History of retinal repair
• Malignancy:
• Active
• Tumor-related chemotherapy within the prior 6 months
• Therapeutic radiation to the central nervous system within the prior year
• Current diagnosis of bipolar disorder type I or schizophrenia as determined by responses to inquiry: Have you ever been diagnosed or prescribed medications for bipolar disorder or schizophrenia?
• Chronic use of supplemental oxygen or hypoxemia while breathing room air.
• Untreated asthma/Bronchial obstruction/pulmonary blebs, recent/untreated pneumothorax
• Congestive heart failure with ejection fraction \< 40%
• Any implanted devices not cleared for hyperbaric pressurization\*.
• Epilepsy and/ or seizures

Sponsors & Collaborators

• University of South Florida: lead
• James A. Haley Veterans' Hospital (JAHVH): collaborator

Study Sites (1)

University of South Florida

Tampa, Florida, 33612, United States

RECRUITING

Related Publications (3)

• Ajayi OD, Gaskill Z, Kelly M, Logue CJ, Hendricksen SM. A comparison of two hyperbaric oxygen regimens: 2.0 ATA for 120 minutes to 2.4 ATA for 90 minutes in treating radiation-induced cystitis Are these regimens equivalent? Undersea Hyperb Med. 2020 Fourth Quarter;47(4):581-589. doi: 10.22462/10.12.2020.7.

  PMID: 33227834 BACKGROUND

• Daly S, Thorpe M, Rockswold S, Hubbard M, Bergman T, Samadani U, Rockswold G. Hyperbaric Oxygen Therapy in the Treatment of Acute Severe Traumatic Brain Injury: A Systematic Review. J Neurotrauma. 2018 Feb 15;35(4):623-629. doi: 10.1089/neu.2017.5225. Epub 2018 Jan 22.

  PMID: 29132229 BACKGROUND

• Loignon A, Ouellet MC, Belleville G. A Systematic Review and Meta-analysis on PTSD Following TBI Among Military/Veteran and Civilian Populations. J Head Trauma Rehabil. 2020 Jan/Feb;35(1):E21-E35. doi: 10.1097/HTR.0000000000000514.

  PMID: 31479073 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Central Study Contacts

Erik Velasquez

CONTACT

813-905-1043; erikv@usf.edu

Rachel A Karlnoski, PhD

CONTACT

7278584224; karlnosk@usf.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To reduce performance bias participants will blinded to condition. To reduce detection bias, investigators, Independent Evaluators (IE), and data analysts will also be blinded to treatment condition (i.e. HBOT or placebo/sham group). Treatments will be coded in the database (E.g., treatment A or B). Because the primary and secondary outcome data will be collected using a self-report questionnaire, the possibility of interpretation does not exist. Only in case of safety issues, the patient assignment could be unblinded.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair Department of Neurosurgery and Brain Repair

Model Details: Blinded Group Sequential Adaptive Randomized Controlled Trial

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 30, 2024
• Study Start: September 18, 2024
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): August 15, 2029
• Last Updated: November 19, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)