Clinical trial NCT05173818: Hyperbaric Oxygen Effects on Persistent Post-concussive Symptoms
Official title: Effect of Hyperbaric Oxygen on Persistent Post-concussive Symptoms After Mild Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Persistent Post-concussive Syndrome
Concussion Post Syndrome
Keywords: Hyperbaric oxygen treatment
Neurofilament light chain
RBANS
Lead sponsor: Essentia Health
Sponsor class: OTHER
Collaborators: name: University of North Dakota
name: Dakota Medical Foundation
name: The Swanson Foundation
name: State of North Dakota
First posted: 2021-12-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

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.

Detailed description: This is a parallel, randomized, double-blinded and sham-controlled study. A total of 100 subjects will be randomly assigned to either an intervention arm: 50 participants exposed to \> 99.9% oxygen at 1.5 atmosphere absolute for 60 minutes over 40 treatments or sham-treatment arm: 50 participants exposed to oxygen and pressure composition equivalent to breathing atmospheric air for 60 minutes over 40 treatments.

This study is designed to determine whether hyperbaric oxygen improves neuropsychological status and ameliorates symptoms in adults with persistent post-concussive symptoms (PPCS) following mild traumatic brain injury. It recruits from either military or civilian population; uses a validated screening tool - Repeatable battery for the assessment of neuropsychological status (RBANS)- used in dementia and other forms of brain injury not used hitherto, in previous randomized control trial that investigated the effectiveness of hyperbaric oxygen in the management of PPCS. It also includes a concssuon biomarker, as an objective secondary endpoint.

The study is based on repeated measure design. The study will describe and track changes in the outcomes of interest over time, and examine associations between measures within each participant and across certain participant characteristics.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* History of brain injury not of traumatic etiology such as stroke or drug-induced coma
* Verifiable diagnosis of learning disability. Other pre-existing cognitive issues may make it difficult for potential participants to fill out certain outcome assessments such as neurobehavioral symptomatic inventory. This could lead to measurement bias or confound the result.
* Claustrophobia and unwilling to enter hyperbaric chamber
* Untreated pneumothorax
* Presence of implanted device with un-verifiable test to pressure by manufacturer
* Concurrent enrollment in an alternate interventional trial for post concussive symptoms

Primary outcomes:
measure: Changes in Repeatable battery for the assessment of neuropsychological status (RBANS)
timeFrame: Baseline, 1-week, 13-week, 18-month
Secondary outcomes:
measure: Changes in serum Neurofilament Light chain (NfL) level
timeFrame: Baseline, 1-week, 13-week, 18-month
measure: Changes in Pittsburg Sleep Quality Index (PSQI) score
timeFrame: Baseline, 1-week, 13-week, 18-month
measure: Changes in Neurobehavioral Symptom Inventory (NSI) scores
timeFrame: Baseline, 1-week, 13-week, 18-month
measure: Changes in reported PTSD-Civilian version (PCL-C) measures
timeFrame: Baseline, 1-week, 13-week, 18-month
measure: Changes in World Health Organization Quality of Life -BREF (WHOQOL-BREF) domain scores
timeFrame: Baseline, 1-week, 13-week, 18-month
Other outcomes:
Locations:
city: Fargo
country: United States
facility: Essentia Health
state: North Dakota
Study officials:
affiliation: Essentia Health
name: Olayinka D Ajayi, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Dakota
name: Marc Basson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Dakota
name: Marilyn Klug, PhD
role: STUDY_CHAIR
affiliation: Essentia Health
name: Paulina Kunecka, MD
role: STUDY_CHAIR
affiliation: University of North Dakota
name: Richard Ferraro, PhD
role: STUDY_CHAIR
affiliation: Center for Rural Health, University of North Dakota
name: Rebecca Quinn, MSW, LMSW
role: STUDY_CHAIR
affiliation: Essentia Health
name: Sharon Hanson, RN
role: STUDY_DIRECTOR
References:
citation: Moser RS, Schatz P. Enduring effects of concussion in youth athletes. Arch Clin Neuropsychol. 2002 Jan;17(1):91-100.
citation: 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.
citation: 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.
citation: 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.