Biomarkers in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Trial (BioBOOST)

Biomarkers in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Trial (BioBOOST)

BioBOOST is a multicenter, observational study of the effect of derangements in brain physiologic parameters on brain injury biomarker levels in patients with severe traumatic brain injury.

Study Overview

• Status: Recruiting
• Conditions: TBI (Traumatic Brain Injury)
• Intervention / Treatment: Other: No intervention. This is an observational study.

Detailed Description

This study is a prospective observational, multi-center study of subjects enrolled in the Brain Oxygen Optimization in Severe Traumatic Brain Injury-Phase 3 (BOOST-3) trial. BOOST-3 is a multicenter, randomized, blinded-endpoint, comparative effectiveness study of goal-directed critical care based upon monitoring of brain tissue oxygen and intracranial pressure versus monitoring of intracranial pressure alone in patients with severe traumatic brain injury.

The investigators will obtain an initial set of biospecimens (serum, plasma, cerebrospinal fluid (CSF), DNA and RNA) shortly after randomization into BOOST-3 and within 24 hours of injury. Subsequent biospecimens will be obtained every 8 hours for the first 24 hours post-enrollment. This will allow the characterization of acute changes in biomarker levels. On study days 2 through 5, biospecimens will be obtained twice a day to allow characterization of sub-acute changes in biomarker levels, without overburdening study teams or taking too much blood from individual subjects. On study days 7 and 14 and at 6-months post-enrollment, one set of biospecimen will be obtained, preferably in the morning. Biospecimens collected at each time point will consist of 6 ml of whole blood for serum extraction, 6 ml of whole blood for plasma extraction, 2.5 ml of whole blood for RNA extraction (a total of 14.5 ml [one tablespoon] of blood) and 5 ml of cerebrospinal fluid (CSF).

BioBOOST will utilize data collected in the BOOST-3 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.

BioBOOST will also utilize outcome assessment data collected from BOOST-3 participants at 6 months after injury (180 Days ± 30 days). Trained study personnel who are blinded to the treatment arm will administer the outcome assessments, which will include the measures listed below. The battery includes measures of functional status (GOSE), cognition, and emotional health. The 6-month follow-up interview will be done in person whenever possible. It may be done by telephone or video conference with participants where an in-person interview is not possible.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Ramon Diaz-Arrastia, MD, PhD; Phone Number: 215-662-9732; Email: Ramon.Diaz-Arrastia@pennmedicine.upenn.edu
• Study Contact Backup: Name: Cynthia Diaczynsky; Email: cynthia.diaczynsky@pennmedicine.upenn.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Not yet recruiting
      • University of Michigan
      • Contact: Fred Korley, MD, PhD; Email: korley@med.umich.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Penn Presbyterian Medical Center
      • Contact: Ramon Diaz-Arrastia, MD, PhD; Phone Number: 800-789-7366; Email: Ramon.Diaz-Arrastia@pennmedicine.upenn.edu
      • Principal Investigator: Ramon Diaz-Arrastia, MD, PhD
      • Sub-Investigator: Danielle Sandsmark, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The investigators plan to enroll a maximum of 300 male and female subjects among multiple clinical sites.

Description

Inclusion Criteria:

• Enrolled in BOOST-3 (this is an ancillary study to the BOOST-3 trial)
• BOOST-3 participant is enrolled at a BioBOOST site
• Able to maintain initial blood sample within 24 hours of injury
• Provide proxy informed consent

Exclusion Criteria:

• Profoundly anemic (subjects who are profoundly anemic require blood transfusion)
• Age less than 18 years

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe traumatic brain injury (TBI); This observational study is ancillary to the Brain Oxygen Optimization in Severe TBI Phase 3 (BOOST-3) trial (NCT 03754114). All participants in Bio-BOOST are enrolled in BOOST-3.	Other: No intervention. This is an observational study.; There are no interventions being tested in the Bio-BOOST study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak levels of glial fibrillary acidic protein (GFAP)	This hypothesis will be tested via linear regression model, with peak GFAP level as the response variable and hypoxia exposure as the predictor of interest. Hypoxia exposure will be defined as the depth and duration of PbtO2 < 20 mmHg during the first 48 hours of injury, quantified using area under the curve (AUC) methodology.	First 5 days after injury
Peak levels of ubiquitin C-terminal hydrolase L1 (UCH-L1)	This hypothesis will be tested via linear regression model, with peak UCH-L1level as the response variable and hypoxia exposure as the predictor of interest. Hypoxia exposure will be defined as the depth and duration of PbtO2 < 20 mmHg during the first 48 hours of injury, quantified using AUC methodology.	First 5 days after injury
Peak levels of neurofilament light chain (NfL)	This hypothesis will be tested via linear regression model, with peak NfL level as the response variable and hypoxia exposure as the predictor of interest. Hypoxia exposure will be defined as the depth and duration of PbtO2 < 20 mmHg during the first 48 hours of injury, quantified using AUC methodology.	First 5 days after injury
Peak levels of Tau	This hypothesis will be tested via linear regression model, with peak Tau level as the response variable and hypoxia exposure as the predictor of interest. Hypoxia exposure will be defined as the depth and duration of PbtO2 < 20 mmHg during the first 48 hours of injury, quantified using AUC methodology.	First 5 days after injury

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Medical University of South Carolina; University of Pittsburgh; University of Michigan

Publications and helpful links

General Publications

• Okonkwo DO, Shutter LA, Moore C, Temkin NR, Puccio AM, Madden CJ, Andaluz N, Chesnut RM, Bullock MR, Grant GA, McGregor J, Weaver M, Jallo J, LeRoux PD, Moberg D, Barber J, Lazaridis C, Diaz-Arrastia RR. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial. Crit Care Med. 2017 Nov;45(11):1907-1914. doi: 10.1097/CCM.0000000000002619.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Biomarkers
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: 00042151

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Non-identified IPD will be made available through the Federal Interagency TBI Research (FITBIR) Database.
• IPD Sharing Time Frame: Data will become available upon completion of the study in December of 2026.
• IPD Sharing Access Criteria: FITBIR qualified investigators will be provided access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No