Clinical trial NCT04602806: Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Precision Medicine Phase 2 Option 1
Official title: TRACK-TBI Precision Medicine Phase 2-Option I
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Traumatic Brain Injury
Keywords: Traumatic Brain Injury
Biomarkers
Neuroimaging
Psychological Health
Concussion
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: U.S. Army Medical Research and Development Command
First posted: 2020-10-26
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a population-based TBI study. All patients presenting with traumatic brain injury and receive a head CT scan as part of standard care within 6 hours of injury are initially eligible.

Brief summary: This study is being conducted to validate early and ultra-early blood-based and novel imaging biomarkers of Diffuse Axonal Injury (DAI), Microvascular Injury (MVI), and neuroinflammation that may serve as predictive and pharmacodynamic biomarkers in a new cohort of moderate-severe TRACK-TBI subjects. The study team will enroll a cohort of moderate to severe TBI subjects (N=50), stratified according to VA/DoD criteria for these injury severities through the existing TRACK-TBI network sites to obtain novel advanced neuroimaging and more frequent biomarker sampling. Subjects will be assessed over 3 months.

Detailed description: In 2009, the multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury Consortium was implemented to characterize the clinical, magnetic resonance imaging (MRI), and blood-based biomarker features of TBI to inform design of next-generation precision medicine clinical trials in TBI. Over the past 10+ years, TRACK-TBI has been supported by National Institute of Neurological Disorders and Stroke (NINDS), Department of Defense (DoD), Department of Energy (DoE), the National Football League, and other philanthropic and industry partners. TRACK-TBI has enrolled \>3000 control and TBI subjects across the injury spectrum at 18 US Level 1 Trauma Centers. This effort has established the world's largest collection of TBI imaging studies and bio-specimens. The study results are already being adopted into clinical research and bedside practice. The TRACK-TBI Consortium is now primed to deliver on critical military and public health knowledge gaps and needs: objective classification of TBI based on what is termed as "mechanistic" endophenotypes, e.g., diffuse axonal injury (DAI), microvascular injury (MVI), and neuroinflammation. An endophenotype is an internal phenotype discoverable by biochemical, physiological, radiological, pathological, or other techniques, which is intermediate between a complex phenotype and the presumptive genetic or environmental contribution to a disease. Endophenotypes are quantitative, continuous variables, unlike a phenotype which is usually a binary, categorical variable. These mechanistic endophenotypes, defined by imaging and blood-based biomarkers, will direct targeted treatments based on mechanism, providing the tools needed for successful execution of precision medicine clinical trials. To achieve the goal of precision medicine in TBI, it is necessary to identify subgroups of TBI patients that will respond to a targeted therapy. Investigators will assess putative blood-based and neuroimaging biomarkers for DAI, MVI, and neuroinflammation. Fluid biomarkers complement imaging markers and may provide important tools for precision medicine clinical trials. Investigators will collect acute data (early and ultra-early i.e., hours-days following injury), to validate the utility of these biomarkers in defining TBI mechanistic endophenotypes for use in clinical trials.

Specific Aim for TRACK-TBI Precision Medicine Phase 2-Option 1: To validate early and ultra-early blood based and novel imaging biomarkers of DAI, MVI, and neuroinflammation that may serve as predictive and pharmacodynamic biomarkers in a cohort of moderate-severe subjects.

Eligibility criteria: Inclusion Criteria:

* Age 18 - 65y inclusive
* History or evidence of TBI, according to DoD-VA criteria
* Glasgow Coma Scale (GCS) 3 - 15 after resuscitation in the ED
* Head CT with evidence of trauma-related abnormality (except for isolated epidural hematoma (EDH))
* Ability to undergo MRI within 48 hours of injury
* Ability to obtain informed consent from participant or Legally Authorized Representative (LAR) within 6 hours of injury
* Fluency in English or Spanish

Exclusion Criteria:

* Unstable respiratory or hemodynamic status
* Evidence of penetrating brain injury
* Isolated EDH as only trauma-related CT abnormality
* Systemic traumatic injury that would preclude participation in study, which is expected to result in long-term disability not related to TBI
* Evidence of serious infectious complications (sepsis, bacteremia, multilobar pneumonia)
* Acute ischemic heart disease (myocardial infarction or unstable angina)
* History of syncope or hypotension
* Systolic blood pressure (SBP) \< 90 mm Hg, Diastolic blood pressure (DBP)\< 40 mm Hg for longer than 5 minutes
* History or evidence of active malignancy
* History of pre-existing neurologic disorder, such as dementia, mild cognitive impairment, uncontrolled epilepsy, multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that may confound interpretation of MRI or neuropsychological results
* History of pre-existing disabling mental illness, such as major depression or schizophrenia
* History or evidence of chronic heart failure or chronic renal failure
* Low likelihood of follow-up (e.g., participant or family indicating low interest, residence in another state or country, unhoused or lack of reliable contacts)
* Women who are pregnant or breast-feeding
* Prisoners or patients in custody
* Patients on psychiatric hold (e.g. 5150, 5250)

Primary outcomes:
measure: Blood Specimen for Analysis of Biomarkers
timeFrame: < 6 hours from the time of TBI
measure: Blood Specimen for Analysis of Biomarkers
timeFrame: 12 hours from the time of TBI
measure: Blood Specimen for Analysis of Biomarkers
timeFrame: 24 hours from the time of TBI
measure: Blood Specimen for Analysis of Biomarkers
timeFrame: Day 2 from the time of TBI
measure: Blood Specimen for Analysis of Biomarkers
timeFrame: Day 3 from the time of TBI
measure: Blood Specimen for Analysis of Biomarkers
timeFrame: Day 5 from the time of TBI
measure: Blood Specimen for Analysis of Biomarkers
timeFrame: Week 4 from the time of TBI
measure: Blood Specimen for Analysis of Biomarkers
timeFrame: Week 6 from the time of TBI
measure: Blood Specimen for Analysis of Biomarkers
timeFrame: 3 Months from the time of TBI
measure: 3 Tesla Brain Structural and Functional Magnetic Resonance Imaging (MRI)
timeFrame: Within 24-48 hours from the time of TBI
measure: 3 Tesla Brain Structural and Functional Magnetic Resonance Imaging (MRI)
timeFrame: 2 Weeks from the time of TBI
measure: 3 Tesla Brain Structural and Functional Magnetic Resonance Imaging (MRI)
timeFrame: 3 Months from the time of TBI
Secondary outcomes:
measure: Glasgow Outcome Scale Extended (GOSE)
timeFrame: 2 Weeks from the time of TBI
measure: Glasgow Outcome Scale Extended (GOSE)
timeFrame: 6 Weeks from the time of TBI
measure: Glasgow Outcome Scale Extended (GOSE)
timeFrame: 3 Months from the time of TBI
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Philadelphia
country: United States
facility: University of Pennsylvania/Penn Presbyterian Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of California, San Francisco
name: Geoffrey T Manley, MD, PhD
role: STUDY_DIRECTOR
affiliation: Baylor College of Medicine
name: Claudia S Robertson, MD
role: STUDY_DIRECTOR
affiliation: University of Pittsburgh Medical Center
name: David O Okonkwo, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Pennsylvania
name: Ramon Diaz-Arrastia, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Washington
name: Nancy R Temkin, PhD
role: STUDY_DIRECTOR
affiliation: University of California, San Francisco
name: Pratik Mukherjee, MD, PhD
role: STUDY_DIRECTOR
affiliation: Harvard Medical School, Spaulding Rehabilitation Hospital
name: Joseph T Giacino, PhD
role: STUDY_DIRECTOR
affiliation: University of California, San Diego
name: Murray B Stein, MD, MPH
role: STUDY_DIRECTOR
affiliation: Medical College of Wisconsin
name: Mike McCrea, PhD, ABPP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Ramesh Grandhi, MD, MS
role: PRINCIPAL_INVESTIGATOR
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