Hyperbaric Oxygen Treatment for Veterans with Traumatic Brain Injury

Phase 3

Recruiting

• Conditions: Traumatic Brain Injury; Military Operations
• Interventions: Drug: Oxygen 99.7 %; Drug: Oxygen 21 %

• Registration Number: NCT06581003
• Lead Sponsor: University of South Florida

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?

* How many HBOT sessions are needed to achieve a significant reduction in neurobehavioral symptoms?

* Does HBOT reduce posttraumatic stress disorder (PTSD) symptoms?

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:

1. Complete baseline assessments to determine eligibility.

2. Attend 40 sessions of HBOT or placebo (normal air) within 12 weeks.

3. Complete questionnaires and interviews throughout the course of the study.

4. Complete a 2-week post treatment visit

Detailed Description

Participants who consent to the study will undergo a comprehensive baseline assessment in two sessions.

Baseline A. This visit will involve questions about the participant's brain injury and relevant medical history, and surveys to learn about symptoms related to the participant's mood, stress, sleep, pain, behaviors (e.g. drug and alcohol use), and life satisfaction. Some surveys may be administered via an interview or as an electronic survey. After Baseline A assessments are completed, the investigators will determine if the participant meets the initial criteria to continue participation.

Baseline B. During this in-person visit, the investigators will have the participant do some thinking exercises by asking him/her to remember words, make decisions about shapes, draw and remember figures, and other similar tasks. The investigators will also draw 30-mL of blood from the participant's arm to detect inflammation and a brief physical exam (e.g. vision test, breathing functioning, heart rate) The participant will have a chance complete optional procedure (described below). After Baseline B, the investigators will determine if the participant is eligible to continue their participation. If the participant is eligible, the next stage is "Randomization" to treatment. If the participant is not eligible, study participation will be over.

Randomization: The participant will be randomized to either HBOT (chamber pressurized to 2 ATA with 100% oxygen) or to a placebo condition (chamber that remains unpressurized and has 21% oxygen). The participant will not get to choose the treatment. The participant nor the PI will know which treatment is received.

HBOT or Placebo Dives: Both conditions will take place in a chamber, and each treatment session is called a "dive". The participant will then complete 40 HBOT or placebo dives in 12 weeks at USF. Every dive, the investigators will record the participant's blood pressure, respiration (breathing) rate, and pulse. If the participant is diabetic, the investigators will also record their glucose levels. Then the participant will change into a medical gown and lay down in a clear chamber for their dive. The participant will be in the chamber for about 72 minutes. Every 5 dives, the participant will complete self-report measures about how they are currently feeling. While the FDA has approved HBOT for some conditions, it is considered an experimental therapy for TBI. The entire visit should last about 90 minutes from self-report measures to getting dressed. The participant's regular medical treatment will not change if they take part in the research.

Mid-treatment Assessments: After the 20th dive is complete, the investigators will ask the participant to complete a mid-treatment assessment visit. The investigators do this to monitor how the participant are feeling and thinking. During this visit the participant will complete many of the same self-report measures and interviews as they did during the baseline visits. The participant will also give another 30-mL of blood at this mid-treatment visit.

Posttreatment Assessments: After the 40 dives are complete, the investigators will ask the participant to complete 1 post-treatment visit at approximately 2 weeks after the last dive. The investigators do this to continue monitoring how the participant is feeling and thinking. During this assessment the participant will complete many of the same self-report measures and interviews as he/she did during the baseline visits and the mid-treatment visit. The participant will also give another 30-mL of blood. After the participant completes the Posttreatments assessments, the investigators will tell him/her which treatment he/she was randomized to receive. If the participant was randomized to the Placebo treatment, he/she will be given the opportunity to receive the actual treatment.

Study Timeline

• Study First Submitted: 2024-08-23
• Study First Submitted QC: 2024-08-28
• Study First Posted: 2024-08-30
• Status Verified: 2024-09
• Study Start: 2024-09-18
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-10-18
• Primary Completion: 2028-08-15
• Study Completion: 2029-08-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 420

Inclusion Criteria

1. U.S. Service Members and Veterans, between 18 and 75 years of age
2. Ability to read, write, and speak English.
3. Ability to provide informed consent.
4. 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).
5. Experiencing chronic symptoms of TBI as determined by at least a NSI total score of >5 [which indicates 2 SDs below the published group means (M=33; SD=14) of those with mild TBI and PTSD; Llop, et al., 2023].
6. Able to tolerate the HBOT environment lying down for one hour.

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Exclusion Criteria

1. Received HBOT within the last 3 months.

2. Concurrently enrolled in another clinical trial.

3. Pregnancy or plans to become pregnant during the study period.

4. Malignancy:

   1. Active
   2. Tumor-related chemotherapy within the prior 6 months
   3. Therapeutic radiation to the central nervous system within the prior year

5. Current diagnosis of bipolar disorder type I or schizophrenia as determined by the Diagnostic Interview for Anxiety, Mood, and OCD and Related Neuropsychiatric Disorders (DIAMOND).

6. Chronic use of supplemental oxygen or hypoxemia while breathing room air.

7. Untreated asthma/Bronchial obstruction/pulmonary blebs, recent/untreated pneumothorax

8. Congestive heart failure with ejection fraction < 40%

9. Any implanted devices not cleared for hyperbaric pressurization.

10. Epilepsy and/ or seizures

11. Scuba diving within the previous month

12. Current suicidal intent as measured by > 3 on the Columbia-Suicide Severity Rating Scale Screener (at phone-screen) .

13. Trapped gas observed indicating Bronchospasm present Tension Pneumothorax

14. Evidence of Noncompliant TM (Until corrected)

15. Evidence of Pneumothorax

16. Evidence of Upper Respiratory Tract Infections

17. Signs and symptoms of viral infections, such as high fevers

18. Emphysema with CO2 retention

19. Optic Neuritis

20. Congenital spherocytosis

21. History of middle ear surgery / disorders

22. Pneumocephalus

23. Optional stool samples will not be collected if someone has diarrhea, vomiting, and took antibiotics in the past 30 days.

24. Antabuse because it predisposes to oxygen toxicity.

25. Any other medications that would lower would predispose to oxygen toxicity.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
HBOT Group	Oxygen 99.7 %	HBOT chamber pressurized to 2.0 ATA with 100% oxygen
Placebo/Sham Group	Oxygen 21 %	HBOT chamber that remains unpressurized and has 21% oxygen

Primary Outcome Measures

Name	Time	Method
Change from Baseline in the Neurobehavioral Symptoms at 2 weeks Post Intervention	at 2 weeks post treatment	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.

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in post traumatic stress disorder symptoms at 2 weeks post intervention	at 2 weeks post treatment	measured by the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM-5); PTSD Checklist-5 (PCL-5). The PTSD Checklist for DSM-5 (PCL-5) is a self-report measure used to assess the presence and severity of PTSD symptoms based on the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). A score between 0-80 Higher Scores: Indicate a worse outcome, as they suggest a greater severity of PTSD symptoms.; Lower Scores: Indicate a better outcome, as they suggest fewer or less severe PTSD symptom

Trial Locations

Locations (1)

University of South Florida; 🇺🇸 Tampa, Florida, United States