Clinical trial NCT04565119: Biomarkers in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Trial
Official title: Biomarkers in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Trial (BioBOOST)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: TBI (Traumatic Brain Injury)
Keywords: Biomarkers
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: University of Michigan
name: University of Pittsburgh
name: Medical University of South Carolina
First posted: 2020-09-25
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: 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 300 male and female subjects among multiple clinical sites.

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak levels of glial fibrillary acidic protein (GFAP)
timeFrame: First 5 days after injury
measure: Peak levels of ubiquitin C-terminal hydrolase L1 (UCH-L1)
timeFrame: First 5 days after injury
measure: Peak levels of neurofilament light chain (NfL)
timeFrame: First 5 days after injury
measure: Peak levels of Tau
timeFrame: First 5 days after injury
Secondary outcomes:
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
Study officials:
References:
citation: 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.