Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Precision Medicine Phase 2 Option 1
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic
Study type: Observational

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.
    

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.
      
Biospecimen description: 
      Plasma and Serum will be collected at each of the following time points: within 6 hours of
      injury, and again at 12h, 24h, 2d, 3d, 5d, 2w, 6w and 3m post-injury. DNA is collected only
      at Day 1 of the Baseline Visit.
    
Keywords: Traumatic Brain Injury; Biomarkers; Neuroimaging; Psychological Health; Concussion