Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Precision Medicine Phase 2 Option 1

NCT ID: NCT04602806

Last Updated: 2025-04-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-06-01
• Study Completion Date: 2030-04-09

Brief 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.

Conditions

Traumatic Brain Injury

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Moderate to Severe TBI Subjects

Adult patients (age 18-65y inclusive) presenting to the Emergency Department (ED) with a history of acute TBI as per American Congress of Rehabilitation Medicine (ACRM) Criteria (i.e., patient has sustained a traumatically-induced physiological disruption of brain function).

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Age 18 - 65y inclusive
• History or evidence of TBI, according to DoD-VA criteria
• Glasgow Coma Scale (GCS) 3 - 15 after resuscitation in the ED
• Head CT with evidence of trauma-related abnormality (except for isolated epidural hematoma (EDH))
• Ability to undergo MRI within 48 hours of injury
• Ability to obtain informed consent from participant or Legally Authorized Representative (LAR) within 6 hours of injury
• Fluency in English or Spanish

Exclusion Criteria

• Unstable respiratory or hemodynamic status
• Evidence of penetrating brain injury
• Isolated EDH as only trauma-related CT abnormality
• Systemic traumatic injury that would preclude participation in study, which is expected to result in long-term disability not related to TBI
• Evidence of serious infectious complications (sepsis, bacteremia, multilobar pneumonia)
• Acute ischemic heart disease (myocardial infarction or unstable angina)
• History of syncope or hypotension
• Systolic blood pressure (SBP) < 90 mm Hg, Diastolic blood pressure (DBP)< 40 mm Hg for longer than 5 minutes
• History or evidence of active malignancy
• History of pre-existing neurologic disorder, such as dementia, mild cognitive impairment, uncontrolled epilepsy, multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that may confound interpretation of MRI or neuropsychological results
• History of pre-existing disabling mental illness, such as major depression or schizophrenia
• History or evidence of chronic heart failure or chronic renal failure
• Low likelihood of follow-up (e.g., participant or family indicating low interest, residence in another state or country, unhoused or lack of reliable contacts)
• Women who are pregnant or breast-feeding
• Prisoners or patients in custody
• Patients on psychiatric hold (e.g. 5150, 5250)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

U.S. Army Medical Research and Development Command

FED

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Geoffrey T Manley, MD, PhD

Role: STUDY_DIRECTOR

University of California, San Francisco

Claudia S Robertson, MD

Role: STUDY_DIRECTOR

Baylor College of Medicine

David O Okonkwo, MD, PhD

Role: STUDY_DIRECTOR

University of Pittsburgh Medical Center

Ramon Diaz-Arrastia, MD, PhD

Role: STUDY_DIRECTOR

University of Pennsylvania

Nancy R Temkin, PhD

Role: STUDY_DIRECTOR

University of Washington

Pratik Mukherjee, MD, PhD

Role: STUDY_DIRECTOR

University of California, San Francisco

Joseph T Giacino, PhD

Role: STUDY_DIRECTOR

Harvard Medical School, Spaulding Rehabilitation Hospital

Murray B Stein, MD, MPH

Role: STUDY_DIRECTOR

University of California, San Diego

Mike McCrea, PhD, ABPP

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Ramesh Grandhi, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of California, San Francisco

San Francisco, California, United States

University of Pennsylvania/Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

University of Utah

Salt Lake City, Utah, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

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Related Links

https://fitbir.nih.gov/content/access-data

Access to FITBIR data will be according to FITBIR policies.

Other Identifiers

W81XWH-18-2-0042

Identifier Type: -

Identifier Source: org_study_id