TRACK-TBI Longitudinal Biomarker Study

Traumatic Brain Injury Clinical Trial

— TRACK-TBI BIO  

Official title:

Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI)- a Longitudinal Biomarker Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05201833
• Other study ID #: 834982
• Secondary ID: U01NS114140
• Status: Enrolling by invitation
• Start date: March 1, 2022
• Est. completion date: February 28, 2027

Study information

• Verified date: June 2023
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 300
• Est. completion date: February 28, 2027
• Est. primary completion date: February 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury

Intervention

Behavioral:
• Telephone Outcome Assessment
Assessments will be administered over the telephone to evaluate participant outcome status
• In-Person Outcome Assessment
Assessments will be administered to evaluate participant outcome status

Procedure:
• 3T Magnetic Resonance Imaging (MRI)
Participants will be asked to complete a 3T MRI
• Blood Draw
Blood Draw for Plasma, DNA, Serum, RNA

Locations

Country	Name	City	State
United States	University of Texas at Austin	Austin	Texas
United States	Spaulding Rehabilitation Hospital	Charlestown	Massachusetts
United States	University of Cincinnati	Cincinnati	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	University of Pennsylvania/Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Utah	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
University of Pennsylvania	National Football League, National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glasgow Outcome Scale Extended (GOSE)	The GOSE provides an overall measure of functional status based on information on cognition, independence, employability, and social/community participation collected via structured interview. Individuals are described by one of the eight outcome categories: Dead (1); Vegetative State (2); Lower Severe Disability (3); Upper Severe Disability (4); Lower Moderate Disability (5); Upper Moderate Disability (6); Lower Good Recovery (7) and Upper Good Recovery (8). Good Recovery is defined as a score of 7-8, Moderate Disability is defined by a score of 5-6 and Severe Disability is defined by a score of 3-4.	~4-6 years post-injury
Secondary	Serum NF-L (neurofilament light chain)	Using advanced blood-based assay platforms, levels of blood biomarkers neurofilament light chain (NF-L) will be measured to validate the utility as a biomarkers for traumatic axonal injury (TAI).	~4-6 years post-injury