Biomarkers in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Trial

TBI (Traumatic Brain Injury) Clinical Trial

— BioBOOST  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04565119
• Other study ID #: 00042151
• Status: Recruiting
• Start date: December 20, 2020
• Est. completion date: December 31, 2027

Study information

• Verified date: April 2024
• Source: University of Pennsylvania
• Contact: Ramon Diaz-Arrastia, MD, PhD
• Phone: 215-662-9732
• Email: Ramon.Diaz-Arrastia[@]pennmedicine.upenn.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• TBI (Traumatic Brain Injury)
• Wounds and Injuries

Intervention

Other:
• No intervention. This is an observational study.
There are no interventions being tested in the Bio-BOOST study.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
University of Pennsylvania	Medical University of South Carolina, University of Michigan, University of Pittsburgh

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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