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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04565119
Recruitment Status : Recruiting
First Posted : September 25, 2020
Last Update Posted : April 16, 2024
Sponsor:
Collaborators:
University of Michigan
University of Pittsburgh
Medical University of South Carolina
Information provided by (Responsible Party):
University of Pennsylvania

Study Description
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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.

Condition or disease Intervention/treatment
TBI (Traumatic Brain Injury) 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 Design
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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarkers in the Brain Oxygen Optimization in Severe Traumatic Brain Injury Trial (BioBOOST)
Actual Study Start Date : December 20, 2020
Estimated Primary Completion Date : December 31, 2026
Estimated Study Completion Date : December 31, 2027

Resource links provided by the National Library of Medicine


Groups and Cohorts
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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.


Outcome Measures
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Primary Outcome Measures :
  1. Peak levels of glial fibrillary acidic protein (GFAP) [ Time Frame: First 5 days after injury ]
    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.

  2. Peak levels of ubiquitin C-terminal hydrolase L1 (UCH-L1) [ Time Frame: First 5 days after injury ]
    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.

  3. Peak levels of neurofilament light chain (NfL) [ Time Frame: First 5 days after injury ]
    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.

  4. Peak levels of Tau [ Time Frame: First 5 days after injury ]
    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.


Biospecimen Retention:   Samples With DNA
Serum/plasma and CSF samples will be analysed for simultaneous measurement of glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L-1 (UCH-L1), tau, and neurofilament light chain (NF-L). These procedures will be carried out in Dr. Diaz-Arrastia's laboratory at the University of Pennsylvania, by a research scientist blinded to the clinical and physiologic data. There will be no difference in the distribution of samples by BOOST-3 treatment group. Other novel brain injury biomarkers will be assayed when they become available. Blood samples collected in the study may be used for both TBI research and the study of other medical conditions.

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04565119


Contacts
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Contact: Ramon Diaz-Arrastia, MD, PhD 215-662-9732 Ramon.Diaz-Arrastia@pennmedicine.upenn.edu
Contact: Cynthia Diaczynsky cynthia.diaczynsky@pennmedicine.upenn.edu

Locations
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United States, Michigan
University of Michigan Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Fred Korley, MD, PhD       korley@med.umich.edu   
United States, Pennsylvania
Penn Presbyterian Medical Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Ramon Diaz-Arrastia, MD, PhD    800-789-7366    Ramon.Diaz-Arrastia@pennmedicine.upenn.edu   
Principal Investigator: Ramon Diaz-Arrastia, MD, PhD         
Sub-Investigator: Danielle Sandsmark, MD, PhD         
Sponsors and Collaborators
University of Pennsylvania
University of Michigan
University of Pittsburgh
Medical University of South Carolina
  Study Documents (Full-Text)

Documents provided by University of Pennsylvania:
Study Protocol and Statistical Analysis Plan  [PDF] June 30, 2020
Informed Consent Form  [PDF] February 25, 2020

More Information
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Publications:

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT04565119    
Other Study ID Numbers: 00042151
First Posted: September 25, 2020    Key Record Dates
Last Update Posted: April 16, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Non-identified IPD will be made available through the Federal Interagency TBI Research (FITBIR) Database.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data will become available upon completion of the study in December of 2026.
Access Criteria: FITBIR qualified investigators will be provided access.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Pennsylvania:
Biomarkers
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Brain Diseases
 Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System