Clinical trial NCT04855396: The Biomarkers in the Hyperbaric Oxygen Brain Injury Treatment Trial (BioHOBIT)
Official title: The Biomarkers in the Hyperbaric Oxygen Brain Injury Treatment Trial (BioHOBIT)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Traumatic Brain Injury
Keywords: Monitoring Biomarkers
Predictive Biomarkers
Glial Fibrillary Acidic Protein
Neurofilament Light Chain
High Sensitivity C-Reactive Protein
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2021-04-22
Enrollment: 150
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The investigators plan to enroll a maximum of 150 male and female subjects among multiple clinical sites.

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.

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

Primary outcomes:
measure: Unfavorable Neurologic Outcome
timeFrame: 6-months post injury
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Medical Center - Hillcrest Hospital
state: California
city: West Palm Beach
country: United States
facility: St. Mary's Medical Center
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky Hospital
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Detroit
country: United States
facility: Detroit Receiving Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Columbus
country: United States
facility: OSU Wexner Medical Center
state: Ohio
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
Study officials:
affiliation: University of Michigan
name: Frederick Korley, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: William Barsan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hennepin Healthcare
name: Gaylan Rockswold, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kansas
name: Byron Gajewski, PhD
role: PRINCIPAL_INVESTIGATOR
References: