Clinical trial NCT05201833: TRACK-TBI Longitudinal Biomarker Study
Official title: Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI)- a Longitudinal Biomarker Study
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Traumatic Brain Injury
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Football League
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2022-01-21
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants enrolled in TRACK-TBI

Brief summary: The overarching goal of this study is to improve understanding of the long-range natural history of TBI by extending follow-up of a previously enrolled cohort (TRACK-TBI) beyond the first 12 months after injury.

Detailed description: This longitudinal observational study is part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) initiative, a multi-institutional project designed to characterize the acute and longer-term clinical, neuroimaging, and blood biomarker features of TBI. TRACK-TBI enrolled TBI patients at 18 Level 1 Trauma Centers in the US, across the age and injury spectrum. This study will extend the follow-up period for TRACK-TBI participants. The extensive clinical, imaging, and biomarker data that has already been collected in these TRACK-TBI participants, in combination with the extended longitudinal data, will allow for the identification of risk factors, co-morbidities, and prognostic biomarkers of TBI. Consequently, the extension of study follow-up will help to determine negative neurological and psychological outcomes of individuals who experienced a TBI compared to healthy and orthopedic controls.

TBI is a complex disease process, in which diverse injury subtypes and multiple molecular mechanisms overlap. There is a need to identify and measure these subtypes, in order to develop precision medicine approaches where specific pathobiological processes are targeted by mechanistically appropriate therapies. The absence of validated biomarkers in the neurotrauma field is a barrier to drug development in this area, and there are currently no disease-modifying therapies that limit the burden of TBI. Biomarkers specific for injury mechanisms should be identified to select participants for clinical trials of targeted therapies (prognostic biomarkers), as well as to confirm target engagement and biological efficacy (pharmacodynamic biomarkers).

Traumatic axonal injury (TAI) is a common pathologic consequence of TBI, and underlies some of the most disabling consequences of injury, including cognitive and affective problems. TAI progresses for years after injury in a subset of patients, and is a key mechanism for long-term neurodegeneration after TBI. Recent breakthroughs in pre-clinical models indicate that novel therapeutic interventions, including strategies such as targeting the mitochondrial transition pore, or promoting axonal maintenance factors are effective in promoting resilience of injured axons and improving neurologic outcome after experimental TBI. Translation of such promising therapies into clinical trials will require prognostic biomarkers that can measure TAI in individual patients, so they can be selected for early phase studies of axon-protective therapies, as well pharmacodynamic biomarkers than can measure the biologic efficacy of such treatments. 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, while robust, is poorly suited for dynamic longitudinal assessments, and measures the end-result of axonal degeneration, rather than an early step in the neurodegenerative process. Recently, the ability to assay axonal proteins in peripheral blood has made it potentially feasible to assess of TAI rapidly, inexpensively, and longitudinally. The axonal protein that holds the most promise as a biomarker of axonal degeneration is neurofilament light chain (NF-L). This project aims to address the gaps in the existing literature regarding specific biomarkers for injury mechanisms and outcomes following TBI. Furthermore, it is likely that a sophisticated understanding of the subtypes and molecular mechanisms of TBI will be required to successfully develop therapies to treat these subtypes.

Eligibility criteria: Inclusion Criteria:

* LONGITUDINAL Telephone Assessment:
* Participated in TRACK-TBI,
* At least two years post injury, and
* Completed at least 1 GOSE during the TRACK-TBI follow-up assessments
* LONGITUDINAL BIOMARKER In-Person Assessment:

Must complete at least one Longitudinal Telephone Assessment and fall into one of the following groups:

* Group 1- Completed TRACK-TBI 6M MRI and are stable or improved with regard to Criteria for Establishing Decline
* Group 2- Criteria for Establishing Decline met when comparing the Telephone Assessments to the last completed TRACK-TBI assessment
* Group 3- All TRACK-TBI orthopedic controls

Ability of participant or legally authorized representative to provide informed consent

Exclusion Criteria:

* Dementia diagnosed prior to the index TBI

Primary outcomes:
measure: Glasgow Outcome Scale Extended (GOSE)
timeFrame: ~4-6 years post-injury
Secondary outcomes:
measure: Serum NF-L (neurofilament light chain)
timeFrame: ~4-6 years post-injury
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Charlestown
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania/Penn Presbyterian Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Austin
country: United States
facility: University of Texas at Austin
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Pennsylvania
name: Ramon Diaz-Arrastia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: