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

NCT ID: NCT04855396

Last Updated: 2025-06-27

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-01-19
• Study Completion Date: 2027-08-31

Brief Summary

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

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.

Conditions

Traumatic Brain Injury

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with Severe Traumatic Brain Injury

Participants will be enrolled in the HOBIT trial

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Frederick Korley, MD, PhD

Associate Professor of Emergency Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frederick Korley, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

William Barsan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Gaylan Rockswold, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hennepin Healthcare

Byron Gajewski, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Kansas

Locations

UCSD Medical Center - Hillcrest Hospital

San Diego, California, United States

Site Status: RECRUITING

St. Mary's Medical Center

West Palm Beach, Florida, United States

Site Status: RECRUITING

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status: RECRUITING

University of Kentucky Hospital

Lexington, Kentucky, United States

Site Status: RECRUITING

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status: RECRUITING

Detroit Receiving Hospital

Detroit, Michigan, United States

Site Status: RECRUITING

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status: RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status: SUSPENDED

Duke University Hospital

Durham, North Carolina, United States

Site Status: NOT_YET_RECRUITING

OSU Wexner Medical Center

Columbus, Ohio, United States

Site Status: SUSPENDED

Hamilton General Hospital

Hamilton, Ontario, Canada

Site Status: SUSPENDED

Countries

United States; Canada

Central Contacts

Natalie Fisher

Role: CONTACT

brownnat@med.umich.edu

734-232-2012

Frederick Korley, MD, PhD

Role: CONTACT

korley@med.umich.edu

734-647-0261

Facility Contacts

Jessica Weaver

Role: primary

Robert Borrego

Role: primary

Nick Mohr

Role: primary

David Dornbos

Role: primary

Kinjal Sethuraman

Role: primary

Anthony Lagina

Role: primary

Thomas Bergman

Role: primary

Katherine Colton

Role: primary

Other Identifiers

Pro00024234

Identifier Type: -

Identifier Source: org_study_id