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Hyperbaric Oxygen Effects on Persistent Post-concussive Symptoms

Phase 2
Active, not recruiting
Conditions
Concussion Post Syndrome
Persistent Post-concussive Syndrome
Interventions
Registration Number
NCT05173818
Lead Sponsor
Essentia Health
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
40
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
HBO at 1.5 Atmosphere absoluteHyperbaric oxygen at 1.5 ATAParticipants 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
Sham control initially at 1.2 then changed to 1.0 ATASham treatmentParticipants 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
Primary Outcome Measures
NameTimeMethod
Changes in Repeatable battery for the assessment of neuropsychological status (RBANS)Baseline, 1-week, 13-week, 18-month

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.

Secondary Outcome Measures
NameTimeMethod
Changes in Pittsburg Sleep Quality Index (PSQI) scoreBaseline, 1-week, 13-week, 18-month

A validated self-rated subjective questionnaire comprising 19 individual questions that generate seven "component" scores {sleep quality, latency, duration, efficiency, disturbances, use of sleep medication and daytime dysfunction}. Persistent post-concussive symptoms following mild TBI usually affects several domains and patients could present with sleep disturbances, cognitive deficits, headache, dizziness, and behavioral changes.

The 19 self-rated items are combined to form seven component scores; each of which has a range of 0-3 points. (0 = no difficulty, 3 = severe difficulty) and total score ranging from 0 - 21 points. "0" indicating no difficulty and "21" indicating severe difficulty in all areas. Higher scores indicate worse sleep quality

Changes in World Health Organization Quality of Life -BREF (WHOQOL-BREF) domain scoresBaseline, 1-week, 13-week, 18-month

World Health Organization Quality of Life - BREF is a practical abridged version of WHOQOL-100 that includes 26-item grouped into four domains (physical health, psychological, social relationships, environment). WHOQOL-100 has been shown to have good psychometric properties.

WHOQOL-BREF creates a quality of life profile. Two items are examined separately. The other questions are grouped into four domains, and each domain score denote the participant's perception of quality of life in the index domain. The mean score of items within each domain is used to calculate the domain score. Mean scores are then multiplied by 4 in order to make domain scores comparable with the scores used in the WHOQOL-100. Higher domain scores denote higher quality of life.

Changes in Neurobehavioral Symptom Inventory (NSI) scoresBaseline, 1-week, 13-week, 18-month

This is a validated self-report measure of post-concussion symptoms, grouped into 4 cluster (somatosensory, cognitive, affective and vestibular).

Neurobehavioral Symptom Inventor (NSI) is a 22 item symptoms scale, participants will rate the severity of their symptoms in the last 2 weeks on a 5 point likert scale (0=none, 1= mild, 2=moderate, 3=severe, 4=very severe) The NSI total score is a sum of the 22 items (range 0-88). Higher scores indicate more severe symptoms.

Changes in serum Neurofilament Light chain (NfL) levelBaseline, 1-week, 13-week, 18-month

This is a protein marker of neuro-axonal damage that can be measured in serum and CSF. serum NfL has better diagnostic and prognostic utility than other neuro-axonal damage biomarkers such as GFAP, tau, UCH-LI in patients with TBI. There is Class III evidence that it distinguishes patients with mild TBI from healthy controls.

Changes in reported PTSD-Civilian version (PCL-C) measuresBaseline, 1-week, 13-week, 18-month

This is a 17-item validated self-report measure that assesses PTSD symptoms. It is further subcategorized into three clusters (reexperiencing, avoidance, hyperarousal). A total score and cluster scores can be obtained based on DSM-IV-TR criteria.

Participants rate how much they were "bothered by that problem in the past month". Items are rated on a 5-point scale ranging from 1 ("not at all") to 5 ("extremely"). A total score for the PTSD CheckList - Civilian Version (PCL-C) ranges from 17 - 85, and can be obtained by summing the scores from each of the 17 items. Higher scores indicate severe PTSD symptomatology.

Trial Locations

Locations (1)

Essentia Health

🇺🇸

Fargo, North Dakota, United States

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