Transforming Research and Clinical Knowledge in Traumatic Brain Injury
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Study type: Observational

Summary: 
      The overall goal of Transforming Research and Clinical Knowledge in Traumatic Brain Injury
      (TRACK-TBI) study is to determine the relationships among the clinical, neuroimaging,
      cognitive, genetic and proteomic biomarker characteristics for the entire spectrum of TBI
      from concussion to coma. TRACK-TBI will validate biomarkers and outcome measures for clinical
      trials, advance diagnostic and prognostic models for TBI and improve clinical trial design.
      The Investigators are enrolling patients within 24 hours of injury who present to a TRACK-TBI
      site with a brain injury that meets ACRM criteria and receives a clinically indicated head
      CT.
    

Detailed description: 
      Effective treatment of traumatic brain injury (TBI) remains one of the greatest unmet needs
      in public health. After 3 decades of failed clinical trials, a new approach is needed. Our
      proposal, Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI),
      establishes a public-private partnership of experienced TBI investigators, and philanthropic
      and industry collaborators, who share a mission to accelerate TBI research. TRACK-TBI will
      create a large, high quality database that integrates clinical, imaging, proteomic, genomic,
      and outcome biomarkers to establish more precise methods for TBI diagnosis and prognosis,
      refine outcome assessment, and compare the effectiveness and costs of TBI care.

      The Investigators hypothesize that this approach will permit investigators to better
      characterize and stratify patients, allow meaningful comparisons of treatments and outcomes,
      and improve the next generation of clinical trials. The Investigators have built on the
      TRACK-TBI Pilot study (NCT01565551) and our team's precompetitive collaboration, forged by
      participation in the TBI Common Data Elements project (TBI-CDE) and the International TBI
      Research Initiative (InTBIR). Having provided the index dataset for the Federal Interagency
      TBI Research database (FITBIR), the Investigators now propose the following Specific Aims:

      Specific Aim 1. To create a widely accessible, comprehensive TBI Information Commons that
      integrates clinical, imaging, proteomic, genomic, and outcome biomarkers from subjects across
      the age and injury spectra, and provides analytic tools and resources to support TBI
      research. Multi- disciplinary teams across 11 sites will enroll 3000 subjects of all ages
      across the injury spectrum of concussion to coma. Utilizing TBI-CDEs, along with uniform
      standards for acquiring multi-site MRI data, the Investigators will expand the TRACK-TBI
      Pilot informatics platform, leveraging existing informatics tools to populate FITBIR,
      yielding a resource for current and future TBI research and international collaboration.

      Specific Aim 2. To validate imaging, proteomic, and genetic biomarkers that will improve
      classification of TBI, permit appropriate selection and stratification of patients for
      clinical trials, and contribute to the development of a new taxonomy for TBI. The
      Investigators hypothesize that validated imaging, proteomic, and genetic biomarkers will
      permit improved patient classification, beyond traditional categories of mild, moderate and
      severe TBI.

      Subaim 2.1. To establish prognostic imaging biomarkers for TBI based on patho-anatomic
      analysis of CT and MRI, as well as quantitative MR volumetrics, diffusion tensor imaging
      (DTI), and resting state functional MRI (R-fMRI).

      Subaim 2.2. To identify blood-based biomarkers that will provide additional diagnostic and
      prognostic information with which to identify TBI phenotypes that can be targeted by specific
      therapies.

      Subaim 2.3. To identify common polymorphisms in candidate genes associated with outcome after
      TBI, and to elucidate causal molecular mechanisms of injury, response, and repair.

      Subaim 2.4. To construct a multidimensional TBI classification system incorporating data from
      multiple domains that will define homogeneous classes of patients suitable for clinical trial
      inclusion.

      Specific Aim 3. To evaluate a flexible outcome assessment battery comprised of a broad range
      of TBI common data elements that enables assessment of multiple outcome domains across all
      phases of recovery and at all levels of TBI severity. When compared with the current gold
      standard, the Glasgow Outcome Scale Extended (GOSE), the Investigators hypothesize that a
      flexible and more discriminating outcome battery reflecting multiple functional domains will
      more precisely and efficiently capture outcomes across the course of recovery, at all levels
      of TBI severity.

      Subaim 3.1. To improve the granularity and breadth of TBI outcomes using a flexible outcome
      assessment battery that enables basic neurocognitive assessment in subjects too impaired to
      undergo standard neuropsychological testing, and comprehensive assessment of cognition,
      functional status, mental health, social participation, and quality of life in those
      cognitively intact enough to provide valid results.

      Subaim 3.2. To determine the efficiency of a flexible outcome assessment battery, as compared
      with the GOSE, in reducing sample sizes needed to detect differences between groups.

      Subaim 3.3. To identify specific TBI phenotypes amenable to targeted interventions, by
      relating patient classification factors (Subaim 2.4) to different outcome factor scores
      (Subaim 3.1).

      Specific Aim 4. To determine which tests, treatments, and services are effective and
      appropriate for which TBI patients, and use this evidence to recommend practices that offer
      the best value. The Investigators will use established comparative effectiveness research
      (CER) and health economics methods to evaluate the ability of each clinical practice to
      improve outcomes while containing costs.

      Subaim 4.1. To identify patients currently admitted to an ICU who could be safely and
      effectively cared for in a floor bed or discharged home with outpatient management, and to
      estimate the health and economic impact of changing the management of these patients.

      Subaim 4.2. To determine whether routine follow up improves TBI outcomes and minimizes their
      economic burden.

      Subaim 4.3. To assess variability in management of patients taking antiplatelet agents at the
      time of TBI, and the effect of management on progression of intracranial hemorrhage, need for
      craniotomy, and outcome.

      The Investigators expect that achievement of these Specific Aims will advance our
      understanding of TBI, improve clinical trial design, lead to more effective patient-specific
      treatments, and improve outcome after TBI.
    

Intervention name(s): In-Person Outcome Assessment; Phone Outcome Assessment; 3T Magnetic Resonance Imaging (MRI); Blood Draw for Plasma, DNA, Serum, RNA
Intervention type(s): Behavioral; Behavioral; Procedure; Procedure
Intervention description(s): NIH Flexible Outcome Assessment Battery Framework Measures In-Person at 2 Weeks, 6 Months, and 12 Months, and by Phone at 3 Months.; NIH Flexible Outcome Assessment Battery Framework Measures by Phone at 2 Weeks, 3 Months, 6 Months, and 12 Months.; 3T Research MRI at 2 weeks and 6 months.; Blood Draw for Plasma, DNA, Serum, RNA at baseline, in hospital (if applicable), 2 weeks, and 6 months (DNA at baseline only).
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The Investigators will enroll patients presenting to the Emergency Department with a
        history of acute TBI within the last 24 hours (acute injury) as per American Congress of
        Rehabilitation Medicine (ACRM) Criteria, in which the patient has sustained a traumatically
        induced* physiological disruption of brain function, as manifested by ≥ one of the
        following:

        Any period of loss of consciousness Any loss of memory for events immediately before or
        after the accident Any alteration of mental state at the time of the accident (feeling
        dazed, disoriented, and/or confused) Focal neurologic deficits that may or may not be
        permanent

        *Traumatically induced includes the head being struck, the head striking an object, or the
        brain undergoing an acceleration/deceleration movement without direct external trauma to
        the head.
      
Biospecimen description: 
      Plasma, Serum, DNA, and RNA will be collected at the time of injury. Plasma, Serum, and RNA
      will be collected at Day 3 and Day 5 if patient is in the hospital, and at 2 weeks and 6
      months post-injury. Samples will be banked at -80 degrees Celsius.
    
Keywords: Traumatic Brain Injury; Biomarkers; Neuroimaging; Psychological Health; Comparative Effectiveness Research