The Biomarkers in the Hyperbaric Oxygen Brain Injury Treatment Trial (BioHOBIT)

There are no therapeutic agents that have been shown to improve outcomes from severe traumatic brain injury (TBI). Critical barriers to progress in developing treatments for severe TBI are the lack of: 1) monitoring biomarkers for assessing individual patient response to treatment; 2) predictive biomarkers for identifying patients likely to benefit from a promising intervention. Currently, clinical examination remains the fundamental tool for monitoring severe TBI patients and for subject selection in clinical trials. However, these patients are typically intubated and sedated, limiting the utility of clinical examinations. Validated monitoring and predictive biomarkers will allow titration of the dose of promising therapeutics to individual subject response, as well as make clinical trials more efficient by enabling the enrollment of subjects likely to benefit. Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and high sensitivity c-reactive protein (hsCRP) are promising biomarkers that may be useful as 1) monitoring biomarkers; 2) predictive biomarkers in severe TBI trials. Although the biological rationale supporting their use is strong, significant knowledge gaps remain. To address these gaps in knowledge, we propose an ancillary observational study leveraging an ongoing severe TBI clinical trial that is not funded to collect biospecimen. The Hyperbaric Oxygen in Brain Injury Treatment (HOBIT) trial, a phase II randomized control clinical trial that seeks to determine the dose of hyperbaric oxygen therapy (HBOT) that that has the highest likelihood of demonstrating efficacy in a phase III trial. The proposed study will: 1) validate the accuracy of candidate monitoring biomarkers for predicting clinical outcome; 2) determine the treatment effect of different doses of HBOT on candidate monitoring biomarkers; and 3) determine whether there is a biomarker defined subset of severe TBI that responds favorably to HBOT. This proposal will: 1) inform a go/no-go decision for a phase III trial of HBOT by providing adjunctive evidence of the effect of HBOT on key biological pathways through which HBOT is hypothesized to affect outcome; 2) provide evidence to support further study of the first monitoring biomarkers of severe TBI; 3) increase the likelihood of success of a phase III trial by identifying the sub-population of severe TBI likely to benefit from HBOT; 4) create a repository of TBI biospecimen which may be accessed by other investigators.

This study is related to NCT04565119

Study Overview

• Status: Recruiting
• Conditions: Traumatic Brain Injury

Detailed Description

The Investigators will obtain an initial set of biospecimens (serum, plasma, CSF, DNA) as soon as feasible after randomization to a HOBIT study arm, but no later than 24 hours from injury. Subsequent biospecimens will be obtained every 8 hours (+/- 1 hour) for the first 24 hours post-enrollment. This will allow the characterization of acute changes in biomarker levels. On study days 2, 3, 5, 7 and 14 biospecimens will be obtained once a day to allow characterization of sub-acute changes in biomarker levels. If feasible, samples should be collected at 8am (+/- 2 hours) to minimize the effects of circadian rhythm on biomarker levels. In addition, during the first 5 days of the study, one set of biospecimen will be collected 4 hours after HBO treatment to examine the acute effects of HBO treatment on biomarkers. This will not apply to those randomized to non-HBOT groups. During the 6-month visit, 1 tablespoon (15 ml) of blood will be collected. In addition, for subjects who have an external ventricular drain in place, 5 cc of CSF will be collected at each time point if feasible. Since subjects are unlikely to have an EVD after the first week post-injury, CSF samples will be collected only for as long as the EVD is in place.

BioHOBIT will utilize data collected in the HOBIT trial. This data includes: demographic data and clinical data such as injury characteristics, vital signs, head CT findings, laboratory data and data on physiologic parameters such as intracranial pressure (ICP), partial pressure of brain tissue oxygen (PbtO2), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP), among others.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Natalie Fisher; Phone Number: 734-232-2012; Email: brownnat@med.umich.edu
• Study Contact Backup: Name: Frederick Korley, MD, PhD; Phone Number: 734-647-0261; Email: korley@med.umich.edu

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Suspended
      • Hamilton General Hospital
• United States
  • California
    • San Diego, California, United States, 92103
      • Recruiting
      • UCSD Medical Center - Hillcrest Hospital
      • Contact: Jessica Weaver
  • Florida
    • West Palm Beach, Florida, United States, 33407
      • Recruiting
      • St. Mary's Medical Center
      • Contact: Robert Borrego
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals & Clinics
      • Contact: Nick Mohr
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky Hospital
      • Contact: David Dornbos
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland Medical Center
      • Contact: Kinjal Sethuraman
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Detroit Receiving Hospital
      • Contact: Anthony Lagina
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Recruiting
      • Hennepin County Medical Center
      • Contact: Thomas Bergman
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Suspended
      • University of Nebraska Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Not yet recruiting
      • Duke University Hospital
      • Contact: Katherine Colton
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Suspended
      • OSU Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The investigators plan to enroll a maximum of 150 male and female subjects among multiple clinical sites.

Description

Inclusion Criteria:

• Enrolled in HOBIT (this is an ancillary study to the HOBIT Trial)

Exclusion Criteria:

• Profoundly anemic (subjects who are profoundly anemic require blood transfusion)
• Blood samples cannot be obtained

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with Severe Traumatic Brain Injury; Participants will be enrolled in the HOBIT trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unfavorable Neurologic Outcome	Glasgow Outcome Scale Extended with a score of <5. Score ranges from 1 to 8, with 1 = death, 8 = Complete Recovery.	6-months post injury

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Frederick Korley, MD, PhD, University of Michigan; Principal Investigator: Gaylan Rockswold, MD, PhD, Hennepin Healthcare; Principal Investigator: Byron Gajewski, PhD, University of Kansas; Principal Investigator: William Barsan, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2021
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: April 18, 2021
• First Submitted That Met QC Criteria: April 18, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 25, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: High Sensitivity C-Reactive Protein; Predictive Biomarkers; Neurofilament Light Chain; Glial Fibrillary Acidic Protein; Monitoring Biomarkers
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries, Traumatic; Wounds and Injuries; Brain Injuries
• Other Study ID Numbers: Pro00024234

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No