Hyperbaric Oxygen Effects on Persistent Post-concussive Symptoms

NCT05173818 | Completed Phase 2 FDA Drug

• 1 other identifier: EH21714
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Persistent post-concussive symptoms (PPCS) are a source of significant burden among a subset of patients with concussion with prevalence rates previously reported between 11 - 82% based on timing of assessment, diagnostic criteria, or population under study. Examples of persistent post-concussion symptoms include balance problems, headaches, fatigue, poor concentration, forgetfulness, anxiety, irritability, and sleep disturbance. Few proposed therapies have proved successful in the management of persistent post-concussion symptoms following mild traumatic brain injury. The investigators will explore hyperbaric oxygen administered in a randomized sham-controlled clinical trial as an effective and tolerable treatment in improving neuropsychological status among adult patients with persistent post-concussive symptoms. The overall hypothesis to be evaluated is that hyperbaric oxygen improves neuropsychological status and a serum concussion biomarker associated with PPCS.

Conditions

Persistent Post-concussive Syndrome; Concussion Post Syndrome

Keywords

Hyperbaric oxygen treatment; Neurofilament light chain; RBANS

Outcome Measures

Primary Outcomes (1)

• Changes in Repeatable battery for the assessment of neuropsychological status (RBANS)

  This is a validated screening tool initially used to assess dementia but has been extended to other neuropsychological conditions, including mild traumatic brain injury. RBANS can assess a broad range of independent neuropsychological domains, a characteristic of mild traumatic brain injury (affects different domains such as sleep, cognition). Alternate forms of RBANS allow for repeated evaluation and sensitivity to milder brain impairment.

  Baseline, 1-week, 13-week, 18-month

Secondary Outcomes (5)

• Changes in serum Neurofilament Light chain (NfL) level

  Baseline, 1-week, 13-week, 18-month

• Changes in Pittsburg Sleep Quality Index (PSQI) score

  Baseline, 1-week, 13-week, 18-month

• Changes in Neurobehavioral Symptom Inventory (NSI) scores

  Baseline, 1-week, 13-week, 18-month

• Changes in reported PTSD-Civilian version (PCL-C) measures

  Baseline, 1-week, 13-week, 18-month

• Changes in World Health Organization Quality of Life -BREF (WHOQOL-BREF) domain scores

  Baseline, 1-week, 13-week, 18-month

Study Arms (2)

HBO at 1.5 Atmosphere absolute

EXPERIMENTAL

Participants in this group will be exposed to hyperbaric oxygen at 1.5 atmosphere absolute (ATA) for 60 minutes per session. Each participant will complete 40 sessions, five sessions per week within 3 months from randomization

Drug: Hyperbaric oxygen at 1.5 ATA

Sham control initially at 1.2 then changed to 1.0 ATA

SHAM COMPARATOR

Participants in this group will be exposed to hyperbaric oxygen at 1.2 atmosphere absolute (ATA) during the first 5 to 7 minutes and the chamber pressure will be reduced to 1.0 ATA for the remaining 53 - 57 minutes for a total of 60 minutes per session. Each participant will complete 40 sessions, five sessions per week within 3 months from randomization

Drug: Sham treatment

Interventions

Hyperbaric oxygen at 1.5 ATA DRUG

Hyperbaric oxygen (HBO2) at 1.5 ATA (active) group (hyperbaric oxygen-chamber compressed to 1.5 atmosphere absolute and breathing \>99.9% oxygen). Each participant should complete 40 sessions, one session per day, five per week over the course of 3 months.

Also known as: 1.5 ATA

HBO at 1.5 Atmosphere absolute

Sham treatment DRUG

Sham treatment includes pressurizing the chamber to 1.2 ATA with air for 5 minutes with noise of circulating air, return the chamber to 1.0 ATA after 5-7 minutes and maintain it at that pressure for until the end of the treatment, with noise of circulating air. Internal control knobs will be concealed. Participants will be instructed to undergo intermittent ear clearing technique during the initial 5 minutes of "descent"

Also known as: 1.2 ATA then changed to 1.0 ATA

Sham control initially at 1.2 then changed to 1.0 ATA

Eligibility Criteria

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

You may qualify if:

• Volunteers must have a history of mild traumatic brain injury, specifically, persistent post-concussive symptoms after examination by a neuropsychologist or neurologist.
• Volunteers time from concussive incident (Mild traumatic brain injury) must be between 3 months - 5 years following head trauma incident
• TBI was caused by non-penetrating trauma
• Volunteers must have current complaints of TBI symptoms such as headache, dizziness, or cognitive or affective problems
• Volunteers must be 18-year-old or more
• Willing and able to provide informed consent
• Able to speak and read English, as primary language
• Agrees to provide blood samples for clinical lab tests
• Willing and committed to comply with research protocol and complete all outcome measures
• Able to equalize middle ear pressures or willing to undergo needle myringotomies if needed
• Willingness and committed to comply with study protocol outlined reproductive plan based on baseline reproductive status

You may not qualify if:

• Prior treatment with hyperbaric oxygen treatment
• Hyperbaric chamber inside attendant, professional, SCUBA diver (technical, commercial, operational/military or recreational)
• The investigators will exclude pregnant women from this study because potential fetal adverse reactions triggered by high oxygen partial pressures such as retrolenticular fibroplasia though careful review of human data are generally reassuring such as the use of hyperbaric oxygen to treat acute carbon monoxide poison in the pregnant patient.13
• Prisoners
• Minors
• Unable to protect airway or requires frequent suctioning
• Known or suspected peri-lymphatic fistula
• Presence of tracheostomy (due to limitations in auto-inflating the middle ear)
• Unable to participate fully in outcome assessments
• Unable to cooperate with hyperbaric oxygen treatments
• Unable to speak and read English, as primary language
• Not cooperating with instructions during hyperbaric oxygen treatments such as bringing contraband items into the chamber (such as fire lighter)
• Not competent to sign their own consent. Such potential participants will not have the capacity to participate in a full range of neurocognitive testing
• Pre-existing diagnosis of a psychotic disorder(s): schizophrenia, bipolar, dissociative disorder
• History of moderate or severe traumatic brain injury

Sponsors & Collaborators

• Dakota Medical Foundation: collaborator
• The Swanson Foundation: collaborator
• State of North Dakota: collaborator
• Essentia Health: lead
• University of North Dakota: collaborator

Study Sites (1)

Essentia Health

Fargo, North Dakota, 58103, United States

Location

Related Publications (4)

• Moser RS, Schatz P. Enduring effects of concussion in youth athletes. Arch Clin Neuropsychol. 2002 Jan;17(1):91-100.

  PMID: 14589756 BACKGROUND

• Shahim P, Politis A, van der Merwe A, Moore B, Chou YY, Pham DL, Butman JA, Diaz-Arrastia R, Gill JM, Brody DL, Zetterberg H, Blennow K, Chan L. Neurofilament light as a biomarker in traumatic brain injury. Neurology. 2020 Aug 11;95(6):e610-e622. doi: 10.1212/WNL.0000000000009983. Epub 2020 Jul 8.

  PMID: 32641538 BACKGROUND

• Cook PA, Johnson TM, Martin SG, Gehrman PR, Bhatnagar S, Gee JC. A Retrospective Study of Predictors of Return to Duty versus Medical Retirement in an Active Duty Military Population with Blast-Related Mild Traumatic Brain Injury. J Neurotrauma. 2018 Apr 15;35(8):991-1002. doi: 10.1089/neu.2017.5141. Epub 2018 Mar 1.

  PMID: 29239267 BACKGROUND

• Weaver LK, Wilson SH, Lindblad AS, Churchill S, Deru K, Price RC, Williams CS, Orrison WW, Walker JM, Meehan A, Mirow S. Hyperbaric oxygen for post-concussive symptoms in United States military service members: a randomized clinical trial. Undersea Hyperb Med. 2018 Mar-Apr;45(2):129-156.

  PMID: 29734566 RESULT

MeSH Terms

Conditions

Post-Concussion Syndrome; Charcot-Marie-Tooth disease, Type 1F

Condition Hierarchy (Ancestors)

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

Study Officials

• Olayinka D Ajayi, MD, MPH

  Essentia Health

  PRINCIPAL INVESTIGATOR

• Marc Basson, MD, PhD

  University of North Dakota

  PRINCIPAL INVESTIGATOR

• Marilyn Klug, PhD

  University of North Dakota

  STUDY CHAIR

• Paulina Kunecka, MD

  Essentia Health

  STUDY CHAIR

• Richard Ferraro, PhD

  University of North Dakota

  STUDY CHAIR

• Rebecca Quinn, MSW, LMSW

  Center for Rural Health, University of North Dakota

  STUDY CHAIR

• Sharon Hanson, RN

  Essentia Health

  STUDY DIRECTOR

Study Design

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

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: December 30, 2021
• Study Start: June 28, 2022
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 6 months after study completion and for 36 months
• Access Criteria: A full description of the intended use of the data must be sent to the corresponding author for review and approval. Participant consent for data sharing is conditioned and new ethics approval may be required.

Locations

US (1)