Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI)

Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI)

Introduction and Consortium History 

The TRACK-TBI Consortium is a partnership of top tier academic and Level 1 Trauma Centers across the United States. Launched in 2009, the TRACK-TBI Pilot study (NIH RC2 NS069409) has:

  • Validated the NINDS TBI Common Data Elements.
  • Collected detailed clinical data on 650 subjects across the injury spectrum, along with CT/MRI imaging, blood biospecimens, and detailed outcomes.
  • Built an infrastructure of integrated clinical databases, imaging repositories, biosample repositories, and coordinated multisite/multidisciplinary expertise.
  • Received ongoing financial and in-kind support from patient advocacy foundations and private industry partners in the neuroimaging, pharmaceutical, device, and data management and analytic spaces

TRACK-TBI expanded to 11 sites with the launch of the TRACK-TBI U01 phase in 2013 (NINDS U01 NS086090). 7 new institutions joined the consortium during the U01 phase (2017), resulting in a total of 18 enrolling clinical sites with additional sites providing analytic support.

Goals:

  • Describe the natural history of TBI.
  • Establish precise methods for TBI diagnosis and prognosis.
  • Refine outcome assessments.
  • Compare effectiveness and costs of TBI care.

The extensive protocols empower rich, multidimensional characterization of the clinical, neuroimaging, and blood-based biomarker features of TBI. TRACK-TBI has amassed the world’s largest and most comprehensive serial collection of standardized TBI neuroimaging (CT and MRI), using structural, functional, and diffusion phantoms for quantitative imaging, and developed automated pipelines for imaging quality assurance. The TRACK-TBI study followed participants longitudinally for one year from time of injury.

With the close of U01 funding in 2018, continued enrollment into the TRACK-TBI protocol was supported by an unrestricted gift from the National Football League (i.e., “Post-U01 cohort” – for more information about this cohort, see the below section “TRACK-TBI U01 vs. “Post-U01”).

As of July 2020, TRACK-TBI U01+Post-U01 has enrolled >3050 TBI subjects and >350 orthopedic control subjects. 

TRACK-TBI Longitudinal (TRACK-TBI LONG)

TRACK-TBI LONG, launched in May 2019, extends follow-up of the deeply phenotyped TRACK-TBI cohort into the chronic phase. This is the first and largest study of incident TBI to couple comprehensive multi-year clinical trajectories with advanced neuroimaging and proteomic biomarkers.

Goals:

  • Connect with participants enrolled in the TRACK-TBI-II study to assess their functional status two or more years after their original study injury.
  • Elucidate TBI’s natural history.
  • Identify individuals most at risk for unfavorable outcomes.
  • Initiate development of diagnostic, prognostic, and therapeutic/ management tools for this heterogeneous condition. 

TRACK-TBI LONG expands upon the original TRACK-TBI study protocol. TBI and Control participants from the TRACK-TBI U01 study as well as participants enrolled under the Post-U01 phase of the study will be eligible for up to 3 annual TRACK-TBI LONG Telephone Assessments.

TRACK-TBI is supported by funding through a competitive grant from the National Football League Scientific Advisory Board.

Clinical Validation of Serum Neurofilament Light as a Biomarker of Traumatic Axonal Injury (TRACK-TBI BIO)

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity and a strong risk factor for neurodegenerative disorders later in life. The absence of validated biomarkers in the neurotrauma field prevents drug development, so there are no disease-modifying therapies that successfully limit the burden of TBI.

Traumatic axonal injury (TAI) underlies the most disabling consequences of TBI. Recent breakthroughs in pre-clinical models indicate that novel therapeutic interventions are effective in promoting resilience of injured axons and improving neurologic outcome after experimental TBI.

Successful translation of these therapies will require prognostic biomarkers that measure TAI in individual patients and pharmacodynamic biomarkers that measure treatment efficacy. Currently, the best biomarker for TAI is fractional anisotropy (FA) and mean diffusivity (MD) of white matter tracts, measured using diffusion tensor imaging (DTI) MRI. This technique is poorly suited for dynamic longitudinal assessments and measures the end-result of axonal degeneration, rather than earlier neurodegenerative stages. The recent ability to assay axonal proteins in peripheral blood has made it possible to assess TAI rapidly, inexpensively, and longitudinally.

Goal:

  • Clinically validate the axonal protein neurofilament light chain (NfL) as a prognostic biomarker of TAI. 

The TRACK-TBI Biomarker Project NF-L (TRACK-TBI BIO NF-L) extends the follow-up periods for TRACK-TBI participants from 1 to 5 years. The clinical, imaging, and biomarker data already collected in these subjects will allow for the identification of risk factors, co-morbidities, and prognostic biomarkers of TBI. The extension of study follow-up will help determine negative neurological and psychological outcomes of individuals who experienced a TBI compared to healthy controls.

A secondary objective is to validate serum NF-L as a biomarker of traumatic axonal injury, and obtain data that will allow us to submit a Qualification Plan to the Center for Drug Evaluation and Research at FDA for qualification of serum- NF-L as a Drug Development Tool.

The TRACK-TBI Biomarker Project Tau/pTau (TRACK-TBI BIO Tau/PTau) aims to validate Tau and P-Tau as prognostic biomarkers for complicated mild TBI.

TRACK-TBI Epileptogenesis Project (TRACK-TBI EPI) 

Post-traumatic epilepsy (PTE) is a common TBI complication, occurring in up to 20% of civilian patients and as many as 50% of military service members who suffer severe brain trauma. Epilepsy resulting from brain trauma is difficult to control with medical therapy and accounts for 5% of patients referred to specialized epilepsy centers.

PTE can arise from TBI of any severity and through a variety of mechanisms, which may co-exist within a single patient. Epileptogenesis can result from penetrating trauma or focal contusions known as focal brain injury. Closed head injury can also produce diffuse injury, with shearing of axons and blood vessels, diffuse edema and ischemia, and secondary cellular damage through the release of inflammatory mediators.

The clinical features of epilepsy such as seizure frequency and severity, prevalence of associated co-morbidities, and responsiveness to therapy, may differ. Additionally, there is variation in neurophysiologic and imaging features of epileptogenicity. Indeed, a sophisticated understanding of the subtypes of epilepsy resulting from brain trauma is required to successfully develop anti-epileptogenic therapies. 

Goal:

  • Determine how PTE contributes to negative neurological and psychological outcomes of individuals who experienced a TBI through comparisons to patients with TBI but without PTE.

Funded in March 2019, TRACK-TBI Epileptogenesis Project (TRACK-TBI EPI) extends the follow-up period of the TRACK-TBI cohort up to 5 years after injury to identify patients who developed PTE. The TRACK-TBI NINDS PTE Screening Questionnaire identifies participants who screen positive for PTE and consent them to undergo a detailed clinical evaluation. Data collected via a combination of follow up phone screening and in-person visits assesses the relationship between TBI severity and epileptogenesis as the primary endpoint. These data will provide the first comprehensive longitudinal phenotyping of subjects with PTE from the moment of TBI through their epilepsy diagnosis and treatment.

Abbott i-STAT

The i-Stat TBI Plasma Test is a biomarker-based assay designed to objectively assess the need for CT.

TRACK-TBI has partnered with Abbott to test its prototype TBI point-of-care device. The i-STAT handheld blood analyzer and blood test can be used at the patient’s bedside to detect elevated levels of TBI biomarkers like GFAP and UCHL-1. 

This is the first rapid handheld TBI blood test, which will help clinicians assess individuals with suspected mild TBIs, including concussions. Tests results are available within 15 minutes after plasma is placed in the test cartridge. The technology could help detect brain injury even if CT scan is normal.

The study aims to enroll ~1100 subjects over 2 years across the Network sites. Six sites are now enrolling participants for this study: UCSF, Universtiy of Pittsburgh Medical Center, Baylor College of Medicine, UT Austin, University of Pennsylvania, and Medical College of Wisconsin.