Hyperbaric Oxygen Therapy for Post-Concussion Syndrome

• ClinicalTrials.gov Identifier: NCT05643482
• Recruitment Status: Not yet recruiting
• First Posted: December 8, 2022
• Last Update Posted: December 8, 2022
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Shanti Pinto, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

The purpose of this study is to decrease symptom burden, improve cognitive function, and improve quality of life outcomes in subjects with mild TBI and persisting post-concussion syndrome using Hyperbaric Oxygen Treatment compared to a sham intervention.

Specific Aims:

1. Evaluate the efficacy of hyperbaric oxygen treatment to improve outcomes for adults with persisting post-concussion syndrome. Specifically, the investigators hypothesize that a prescribed course of hyperbaric oxygen treatments (HBOT) will improve outcomes and quality of life in adults with persisting symptoms >3 months after injury.

   1. Decrease symptom burden as measured by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ).
   2. Improve cognitive function as measured by the National Institutes of Health (NIH) Toolbox Cognition Battery.
   3. Improve quality of life as measured by the 36-Item Short Form Survey (SF-36).
2. Assess the safety and tolerability of hyperbaric oxygen treatments and compliance with treatment in adults with persisting post-concussion syndrome.

Condition or disease	Intervention/treatment	Phase
Post-Concussion Syndrome	Device: Hyperbaric Oxygen Treatment; Other: Placebo gas	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants will be randomized between HBOT and control group with a 1:1 allocation ratio, stratified by decade of age and gender via computer generated block randomization with block size of four.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Hyperbaric Oxygen Therapy for Post-Concussion Syndrome: A Double-Blind, Randomized, Placebo-Controlled Pilot Study
• Estimated Study Start Date: January 2023
• Estimated Primary Completion Date: March 2025
• Estimated Study Completion Date: September 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: HBOT Arm; Pressurized at 2.0 atmospheres absolute of pressure (ATA) Breathe 100% oxygen 90 minute session, 5 days per week, for 20 sessions	Device: Hyperbaric Oxygen Treatment; Pressurization at 2.0 ATA with 100% oxygen
Sham Comparator: Control Arm; Placebo Gas Pressurized at 2.0 ATA Breathe placebo gas system of 10.5% oxygen and 89.5% nitrogen to mimic the partial pressure of oxygen breathed in regular air at sea level pressure 90 minute session, 5 days per week, for 20 sessions	Other: Placebo gas; Pressurization at 2.0 ATA with 10.5% oxygen to mimic normal air

Outcome Measures

Primary Outcome Measures :

1. Change in symptom burden as measured by the Rivermead Post-Concussion Symptoms Questionnaire-3 (RPQ-3) [ Time Frame: Baseline, immediately after treatment ]
   Change in symptom burden is measured by the Rivermead Post-Concussion Symptoms Questionnaire-3 (RPQ-3) which is a 16 item questionnaire of common cognitive, behavioral, and physical symptoms experienced following a mTBI. The RPQ is rated on a 0-4 scale with scores ranging from 0-64. Higher levels of endorsement indicate more severe symptoms. The RPQ-3 is the total score of the first three items of the RPQ and includes "headaches," "feelings of dizziness," and "nausea and/or vomiting."
2. Change in symptom burden as measured by the Rivermead Post-Concussion Symptoms Questionnaire-3 (RPQ-3) [ Time Frame: Baseline, 1 month after treatment ]
   Change in symptom burden is measured by the Rivermead Post-Concussion Symptoms Questionnaire-3 (RPQ-3) which is a 16 item questionnaire of common cognitive, behavioral, and physical symptoms experienced following a mTBI. The RPQ is rated on a 0-4 scale with scores ranging from 0-64. Higher levels of endorsement indicate more severe symptoms. The RPQ-3 is the total score of the first three items of the RPQ and includes "headaches," "feelings of dizziness," and "nausea and/or vomiting."

Secondary Outcome Measures :

1. Change in symptom burden as measured by the Rivermead Post-Concussion Symptoms Questionnaire-13 (RPQ-13) [ Time Frame: Baseline, immediately after last treatment ]
   Change in symptom burden is measured by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) which is a 16 item questionnaire of common cognitive, behavioral, and physical symptoms experienced following a mTBI. The RPQ is rated on a 0-4 scale with scores ranging from 0-64. Higher levels of endorsement indicate more severe symptoms. The RPQ-3 is the total score of the first three items of the RPQ and includes "headaches," "feelings of dizziness," and "nausea and/or vomiting." The RPQ-13 is the total score of the remaining 13 items on the RPQ scale.
2. Change in symptom burden as measured by the Rivermead Post-Concussion Symptoms Questionnaire-13 (RPQ-13) [ Time Frame: Baseline, 1 month after treatment ]
   Change in symptom burden is measured by the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) which is a 16 item questionnaire of common cognitive, behavioral, and physical symptoms experienced following a mTBI. The RPQ is rated on a 0-4 scale with scores ranging from 0-64. Higher levels of endorsement indicate more severe symptoms. The RPQ-3 is the total score of the first three items of the RPQ and includes "headaches," "feelings of dizziness," and "nausea and/or vomiting." The RPQ-13 is the total score of the remaining 13 items on the RPQ scale.
3. Change in quality of life as measured by the Short Form Survey (SF-36) [ Time Frame: Baseline, immediately after treatment ]
   Change in quality of life is measured by the Short Form Survey (SF-36) which consists of 36 items and measures quality of life via eight different domains including vitality, physical functioning, social functioning, emotional role, physical role, general health, social functioning, and mental health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher scores indicating better levels of function and/or better health. A positive change from Baseline indicates improvement.
4. Change in quality of life as measured by the Short Form Survey (SF-36) [ Time Frame: Baseline, 1 month ]
   Change in quality of life is measured by the Short Form Survey (SF-36) which consists of 36 items and measures quality of life via eight different domains including vitality, physical functioning, social functioning, emotional role, physical role, general health, social functioning, and mental health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The higher scores indicating better levels of function and/or better health. A positive change from Baseline indicates improvement.
5. Global Impression of Change (GIC) [ Time Frame: Baseline, after 5 treatment sessions (approximately 1 week after starting treatment) ]
   The Global Impression of Change scale is a seven-point scale in which participants are asked to rate how much the treatment has changed their activity limitations, symptoms, emotions, and overall quality of life. Possible scores range from -3 (very much worse) to +3 (very much better) with 0 being no change.
6. Global Impression of Change (GIC) [ Time Frame: Baseline, after 10 treatment sessions (approximately 2 weeks after starting treatment) ]
   The Global Impression of Change scale is a seven-point scale in which participants are asked to rate how much the treatment has changed their activity limitations, symptoms, emotions, and overall quality of life. Possible scores range from -3 (very much worse) to +3 (very much better) with 0 being no change.
7. Global Impression of Change (GIC) [ Time Frame: Baseline, after 15 treatment sessions (approximately 3 weeks after starting treatment) ]
   The Global Impression of Change scale is a seven-point scale in which participants are asked to rate how much the treatment has changed their activity limitations, symptoms, emotions, and overall quality of life. Possible scores range from -3 (very much worse) to +3 (very much better) with 0 being no change.
8. Global Impression of Change (GIC) [ Time Frame: Baseline, after 20 treatment sessions (approximately 3 weeks after starting treatment) ]
   The Global Impression of Change scale is a seven-point scale in which participants are asked to rate how much the treatment has changed their activity limitations, symptoms, emotions, and overall quality of life. Possible scores range from -3 (very much worse) to +3 (very much better) with 0 being no change.
9. Global Impression of Change (GIC) [ Time Frame: Baseline, 1 month post-treatment ]
   The Global Impression of Change scale is a seven-point scale in which participants are asked to rate how much the treatment has changed their activity limitations, symptoms, emotions, and overall quality of life. Possible scores range from -3 (very much worse) to +3 (very much better) with 0 being no change.
10. Percentage of participant feeling of back to normal, pre-injury self at baseline as assessed based on patient rating [ Time Frame: Baseline ]
    Percentage of participant feeling of back to normal, pre-injury self at baseline is assessed based on patient rating. Participants will be asked to rate what percent they feel back to their normal, pre-injury self at baseline
11. Percent change in participant feeling of back to normal, pre-injury self as assessed based on patient rating [ Time Frame: Baseline, after 5 treatment sessions (approximately 1 week after starting treatment) ]
    Percent change in participant feeling of back to normal, pre-injury self is assessed based on patient rating. Participants will be asked to rate what percent they feel back to their normal, pre-injury self at baseline
12. Percent change in participant feeling of back to normal, pre-injury self as assessed based on patient rating. [ Time Frame: Baseline, after 10 treatment sessions (approximately 2 weeks after starting treatment) ]
    Percent change in participant feeling of back to normal, pre-injury self is assessed based on patient rating. Participants will be asked to rate what percent they feel back to their normal, pre-injury self at baseline
13. Percent change in participant feeling of back to normal, pre-injury self as assessed based on patient rating [ Time Frame: Baseline, after 15 treatment sessions (approximately 3 weeks after starting treatment) ]
    Percent change in participant feeling of back to normal, pre-injury self is assessed based on patient rating. Participants will be asked to rate what percent they feel back to their normal, pre-injury self at baseline
14. Percent change in participant feeling of back to normal, pre-injury self as assessed based on patient rating [ Time Frame: Baseline, after 20 treatment sessions (approximately 4 weeks after starting treatment) ]
    Percent change in participant feeling of back to normal, pre-injury self is assessed based on patient rating. Participants will be asked to rate what percent they feel back to their normal, pre-injury self at baseline
15. Percent change in participant feeling of back to normal, pre-injury self as assessed based on patient rating [ Time Frame: Baseline, 1 month post-treatment ]
    Percent change in participant feeling of back to normal, pre-injury self is assessed based on patient rating. Participants will be asked to rate what percent they feel back to their normal, pre-injury self at baseline
16. Change in psychological/mood symptoms as measured by Brief Symptom Inventory (BSI) scale [ Time Frame: Baseline, immediately after last treatment ]
    Change in psychological/mood symptoms is measured by Brief Symptom Inventory (BSI) scale. The Brief Symptom Inventory (BSI) (secondary outcome): contains 18 items with 3 subscales measuring Depression, Anxiety, and Somatization and total raw score represents the Global Severity Index (GSI). Scores on each of the 3 subscales range from 0-24 and total GSI scores range from 0-72. Higher scores on the subscales and total GSI are indicative of more severe psychological/mood symptoms
17. Change in psychological/mood symptoms as measured by Brief Symptom Inventory (BSI) scale [ Time Frame: Baseline, 1 month after treatment ]
    Change in psychological/mood symptoms is measured by Brief Symptom Inventory (BSI) scale. The Brief Symptom Inventory (BSI) (secondary outcome): contains 18 items with 3 subscales measuring Depression, Anxiety, and Somatization and total raw score represents the Global Severity Index (GSI). Scores on each of the 3 subscales range from 0-24 and total GSI scores range from 0-72. Higher scores on the subscales and total GSI are indicative of more severe psychological/mood symptoms
18. Number of participants with adverse events [ Time Frame: 1 month after treatment ]
    Safety (Tolerability) of the treatment is assessed by monitoring and evaluating Adverse events (AE)s by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for 30 days post-treatment
19. Number of participants who missed the treatment [ Time Frame: 5 weeks ]
    The count of participants who missed the treatment is assessed.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Must have been evaluated within 48 hours of injury and given a diagnosis of concussion by a medical professional
• Must be experiencing persistent symptoms 3-12 months after injury as defined as having at least symptoms that are moderate to severe (score 3-4) OR at least a total score of 10 with at least 1 symptom rated moderate to severe (3-4) on the Rivermead Post-Concussion Questionnaire (RPQ).

Exclusion Criteria:

Clinically significant cardiac, neurological, psychological/psychiatric, or respiratory impairment in the opinion of the investigators, including but not limited to:

1. Pulmonary:

   • COPD with CO2 retention; previous/current imaging showing hyperinflation/air trapping/bullous disease/blebs
   • Current pneumothorax or previous spontaneous pneumothorax

2. Cardiac:

   • Uncontrolled HTN (systolic >180 or diastolic >100)
   • Known Ejection fraction < 35%
   • Pacemaker / ICD in place (not approved for chamber use)

3. Hematological/Oncological:

   • Current chemotherapeutic drug use, and past history of bleomycin use.
   • Hereditary Spherocytosis
   • Sickle cell anemia

4. Neurological and Psychological:

   • Implanted nerve stimulators
   • Uncontrolled seizure disorder
   • Drug or alcohol abuse/dependence
   • Current treatment for alcohol cessation with disulfiram
   • Claustrophobia

5. Head and Neck:

   • Inability to equilibrate the pressure of middle ears and sinuses
   • Current or previous retinal detachment
   • Retinal or vitreous surgery within the past 3 months

6. Miscellaneous:

   • Current fever or active infection
   • Implanted devices not on the approved list for use with HBOT
   • Women who are pregnant. Women with childbearing potential are required to use effective birth control if not surgically sterile or postmenopausal for >2 years.
   • Undergoing vestibular or other therapy during the intervention
   • Planning a change in medication during the intervention

7. Relative exclusion criteria: Diagnosis of the conditions listed below will require approval of the hyperbaric medicine physician for enrollment into the study.

   • Asthma
   • Optic neuritis
   • Otosclerosis surgery
   • Thoracic surgery
   • Chronic sinusitis

8. Medications: Individuals with recent (within the past six months) or concurrent use of these medications must be approved by the hyperbaric medicine physician.

   • Antabuse - Predisposes to oxygen toxicity
   • Antiseizure medications - Potential participants must have levels of their seizure medications checked within a week of their initial screening visit because low levels can predispose to oxygen toxicity. Laboratory testing must be completed by their outside treating physicians to provide to the research staff for review; the study will not obtain labs for monitoring medication levels as part of the inclusion/exclusion criteria
   • Meclizine - Predisposes to oxygen toxicity
   • Bleomycin - May cause pulmonary fibrosis that can lead to air embolism or pneumothorax in the patient receiving hyperbaric oxygen treatment.
   • Certain ointments/creams that cannot be removed - These may be allowed if covered with cotton dressings.
   • Narcotics - Can lead to cessation of the hypoxic respiratory drive.
   • Nitroprusside - HBOT vasoconstrictive effect interacts with nitroprusside's vasodilator effect, making intensive monitoring mandatory.
   • Penicillin - Predisposes to oxygen toxicity
   • Promethazine (Phenergan) - Predisposes to oxygen toxicity.
   • Corticosteroids - Decreases the threshold for oxygen toxicity.
   • Sulfamylon - Promotes CO2 buildup causing peripheral vasodilatation. When coupled with vasoconstriction, results are worse than with using either agent alone. Use silver sulfadiazine instead for wound care.

Contacts and Locations

Contacts

Contact: Charles Kundig; 214/668-8315; Charles.Kundig@UTSouthwestern.edu

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Shanti Pinto, MD; UT Southwestern Medical Center

More Information

• Responsible Party: Shanti Pinto, ASSISTANT PROFESSOR -Physical Medicine and Rehab, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT05643482
• Other Study ID Numbers: STU-2022-0697
• First Posted: December 8, 2022
• Last Update Posted: December 8, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Post-Concussion Syndrome; Syndrome; Disease; Pathologic Processes; Brain Concussion; Head Injuries, Closed; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating