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Hyperbaric Oxygen Effects on Persistent Post-concussive Symptoms (HOINPCS)

Primary Purpose

Persistent Post-concussive Syndrome, Concussion Post Syndrome

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Hyperbaric oxygen at 1.5 ATA

Sham treatment

About this trial

This is an interventional treatment trial for Persistent Post-concussive Syndrome focused on measuring Hyperbaric oxygen treatment, Neurofilament light chain, RBANS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Essentia HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

HBO at 1.5 Atmosphere absolute

Sham control initially at 1.2 then changed to 1.0 ATA

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Changes in serum Neurofilament Light chain (NfL) level

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 Pittsburg Sleep Quality Index (PSQI) score

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 Neurobehavioral Symptom Inventory (NSI) scores

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 reported PTSD-Civilian version (PCL-C) measures

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.

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

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.

Full Information

NCT ID

NCT05173818

First Posted

December 13, 2021

Last Updated

April 6, 2023

Sponsor

Essentia Health

Collaborators

University of North Dakota, Dakota Medical Foundation, The Swanson Foundation, State of North Dakota

1. Study Identification

Unique Protocol Identification Number

NCT05173818

Brief Title

Hyperbaric Oxygen Effects on Persistent Post-concussive Symptoms

Acronym

HOINPCS

Official Title

Effect of Hyperbaric Oxygen on Persistent Post-concussive Symptoms After Mild Traumatic Brain Injury

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 27, 2022 (Actual)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Essentia Health

Collaborators

University of North Dakota, Dakota Medical Foundation, The Swanson Foundation, State of North Dakota

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Persistent Post-concussive Syndrome, Concussion Post Syndrome

Keywords

Hyperbaric oxygen treatment, Neurofilament light chain, RBANS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

HBO at 1.5 Atmosphere absolute

Arm Type

Experimental

Arm Description

Arm Title

Sham control initially at 1.2 then changed to 1.0 ATA

Arm Type

Sham Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Hyperbaric oxygen at 1.5 ATA

Other Intervention Name(s)

1.5 ATA

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Sham treatment

Other Intervention Name(s)

1.2 ATA then changed to 1.0 ATA

Intervention Description

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"

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Changes in serum Neurofilament Light chain (NfL) level

Description

Time Frame

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

Title

Changes in Pittsburg Sleep Quality Index (PSQI) score

Description

Time Frame

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

Title

Changes in Neurobehavioral Symptom Inventory (NSI) scores

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Olayinka D Ajayi, MD, MPH

Phone

7013647555

olayinka.ajayi@essentiahealth.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Olayinka D Ajayi, MD, MPH

Organizational Affiliation

Essentia Health

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Marc Basson, MD, PhD

Organizational Affiliation

University of North Dakota

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Marilyn Klug, PhD

Organizational Affiliation

University of North Dakota

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Paulina Kunecka, MD

Organizational Affiliation

Essentia Health

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Richard Ferraro, PhD

Organizational Affiliation

University of North Dakota

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Rebecca Quinn, MSW, LMSW

Organizational Affiliation

Center for Rural Health, University of North Dakota

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Sharon Hanson, RN

Organizational Affiliation

Essentia Health

Official's Role

Study Director

Facility Information:

Facility Name

Essentia Health

City

Fargo

State/Province

North Dakota

ZIP/Postal Code

58103

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sharon Hanson, RN

Phone

701-364-7555

sharon.hanson2@essentiahealth.org

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The study protocol, statistical plan and consent form will be available on request. Data will be available on aggregate level; data will be deidentified, the full dataset and statistical code will be available upon request

IPD Sharing Time Frame

6 months after study completion and for 36 months

IPD Sharing 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.

Citations:

PubMed Identifier

14589756

Citation

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

Results Reference

background

PubMed Identifier

32641538

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. Erratum In: Neurology. 2021 Mar 23;96(12):593.

Results Reference

background

PubMed Identifier

29239267

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.

Results Reference

background

PubMed Identifier

29734566

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.

Results Reference

result

Learn more about this trial

Hyperbaric Oxygen Effects on Persistent Post-concussive Symptoms

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