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

Traumatic Brain Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04855396
• Other study ID #: Pro00024234
• Status: Recruiting
• Start date: January 19, 2021
• Est. completion date: August 31, 2025

Study information

• Verified date: September 2023
• Source: University of Michigan
• Contact: Natalie Fisher
• Phone: 734-232-2012
• Email: brownnat[@]med.umich.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: August 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury
• Wounds and Injuries

Locations

Country	Name	City	State
Canada	Hamilton General Hospital	Hamilton	Ontario
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	Detroit Receiving Hospital	Detroit	Michigan
United States	Duke University Hospital	Durham	North Carolina
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	University of Kentucky Hospital	Lexington	Kentucky
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UCSD Medical Center - Hillcrest Hospital	San Diego	California
United States	St. Mary's Medical Center	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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