Clinical trial NCT02119182: Transforming Research and Clinical Knowledge in Traumatic Brain Injury
Official title: Transforming Research and Clinical Knowledge in Traumatic Brain Injury
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Traumatic Brain Injury
Keywords: Traumatic Brain Injury
Biomarkers
Neuroimaging
Psychological Health
Comparative Effectiveness Research
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Department of Health and Human Services
First posted: 2014-04-21
Enrollment: 2996
Sex: ALL
Minimum age (years): 1
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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.

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Age 18-100 (some sites also enrolling pediatric patients)
* Documented/verified TBI by ACRM Criteria
* Injury occurred within 24 hours of ED arrival
* Acute brain CT as part of clinical care
* Visual acuity and hearing adequate for outcomes testing
* Fluency in English (some sites also enrolling Spanish speakers)

Exclusion Criteria:

* Significant polytrauma that would interfere with follow-up and outcome assessment
* Prisoners or patients in custody
* Pregnancy in female subjects
* Patients on psychiatric hold (e.g. 5150, 5250)
* Major debilitating baseline mental health disorders (e.g. schizophrenia or bipolar disorder) that would interfere with the validity of outcome assessment due to TBI
* Major debilitating neurological disease (e.g. stroke, CVA, dementia, tumor) impairing baseline awareness, cognition, or validity of outcome assessment due to TBI
* Significant history of pre-existing conditions that would interfere with likelihood of follow-up and validity of outcome assessment due to TBI (e.g. major substance abuse, alcoholism, end-stage cancers, learning disabilities, developmental disorders)
* Contraindications for MR (for CA+MRI cohort)
* Low likelihood of follow-up (e.g. participant or family indicating low interest, residence in another state or country, homelessness or lack of reliable contacts)
* Current participant in an interventional trial (e.g. drug, device, behavioral)
* Non-English speakers as most outcome measures are normed in the English language.

Primary outcomes:
measure: Glasgow Outcome Scale - Extended (GOS-E)
timeFrame: 6 Months
Secondary outcomes:
measure: 3T Brain Structural and Functional Magnetic Resonance Imaging (MRI)
timeFrame: 2 Weeks
measure: Blood Specimen for Analysis of Biomarkers and Genetics
timeFrame: Baseline Visit (In-Hospital)
measure: TRACK-TBI Flexible Outcome Assessment Battery Framework (Composite Measure)
timeFrame: 2 Weeks
measure: TRACK-TBI Flexible Outcome Assessment Battery Framework (Composite Measure)
timeFrame: 3 Months
measure: TRACK-TBI Flexible Outcome Assessment Battery Framework (Composite Measure)
timeFrame: 12 Months
measure: 3T Brain Structural and Functional Magnetic Resonance Imaging (MRI)
timeFrame: 6 Months
measure: Blood Specimen for Analysis of Biomarkers and Genetics
timeFrame: 2 Weeks
measure: Blood Specimen for Analysis of Biomarkers and Genetics
timeFrame: 6 Months
measure: TRACK-TBI Flexible Outcome Assessment Battery Framework (Composite Measure)
timeFrame: 6 Months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: Denver Health and Hospitals Authority
state: Colorado
city: Englewood
country: United States
facility: University of Colorado/Craig Hospital
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Charlestown
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota/Hennepin County Medical Center
state: Minnesota
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 Medical Center
state: Pennsylvania
city: Austin
country: United States
facility: Dell Seton Medical Center
state: Texas
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: Houston
country: United States
facility: TIRR Memorial Hermann
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
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
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of California, San Francisco
name: Geoffrey T. Manley, MD, PhD
role: STUDY_DIRECTOR
affiliation: Baylor College of Medicine
name: Claudia S. Robertson, MD
role: STUDY_DIRECTOR
affiliation: University of Pittsburgh Medical Center
name: David O. Okonkwo, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Pennsylvania
name: Ramon Diaz-Arrastia, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Washington
name: Nancy R. Temkin, PhD
role: STUDY_DIRECTOR
affiliation: University of California, San Francisco
name: Pratik Mukherjee, MD, PhD
role: STUDY_DIRECTOR
affiliation: Harvard Medical School, Spaulding Rehabilitation Hospital
name: Joseph T. Giacino, MD, PhD
role: STUDY_DIRECTOR
affiliation: Harvard Medical School, Massachusetts General Hospital
name: Ann-Christine Duhaime, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California
name: Dana P. Goldman, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California
name: Arthur W. Toga, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Kevin Smith, MSIS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cincinnati
name: Opeolu M. Adeoye, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland, College Park
name: Neeraj Badjatia, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Randall M. Chesnut, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami
name: Gillian A. Hotz, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas
name: Christopher J. Madden, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Commonwealth University
name: Randall E. Merchant, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seton Healthcare Family
name: Alex B. Valadka, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Antwerp University Hospital, Edegem, Belgium
name: Andrew I. Maas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cambridge, Cambridge, United Kingdom
name: David K. Menon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: McGill University
name: Isabelle Gagnon, PhD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Murray B Stein, MD, MPH
role: STUDY_DIRECTOR
affiliation: The University of Texas Health Science Center, Houston
name: Ryan S Kitagawa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas - Austin
name: David M Schnyer, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dell Seton Medical Center
name: Vincent Y Wang, MD, PhD, MBA
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: David W Wright, MD, FACEP
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Michael McCrea, PhD, ABPP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Gregory Hawryluk, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: Richard B Rodgers, MD, FAANS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota/Hennepin County Medical Center
name: Uzma Samadani, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Denver Health and Hospital Authority
name: Mitchell Cohen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver/Craig Hospital
name: Cindy Harrison-Felix, PhD, FACRM
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami
name: Roland Torres, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Korley FK, Jain S, Sun X, Puccio AM, Yue JK, Gardner RC, Wang KKW, Okonkwo DO, Yuh EL, Mukherjee P, Nelson LD, Taylor SR, Markowitz AJ, Diaz-Arrastia R, Manley GT; TRACK-TBI Study Investigators. Prognostic value of day-of-injury plasma GFAP and UCH-L1 concentrations for predicting functional recovery after traumatic brain injury in patients from the US TRACK-TBI cohort: an observational cohort study. Lancet Neurol. 2022 Sep;21(9):803-813. doi: 10.1016/S1474-4422(22)00256-3.
citation: Galimberti S, Graziano F, Maas AIR, Isernia G, Lecky F, Jain S, Sun X, Gardner RC, Taylor SR, Markowitz AJ, Manley GT, Valsecchi MG, Bellelli G, Citerio G; CENTER-TBI and TRACK-TBI participants and investigators. Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation. Lancet Neurol. 2022 Feb;21(2):153-162. doi: 10.1016/S1474-4422(21)00374-4.
citation: Campbell-Sills L, Jain S, Sun X, Fisher LB, Agtarap SD, Dikmen S, Nelson LD, Temkin N, McCrea M, Yuh E, Giacino JT, Manley GT; TRACK-TBI Investigators. Risk Factors for Suicidal Ideation Following Mild Traumatic Brain Injury: A TRACK-TBI Study. J Head Trauma Rehabil. 2021 Jan-Feb 01;36(1):E30-E39. doi: 10.1097/HTR.0000000000000602.
citation: Yue JK, Yuh EL, Korley FK, Winkler EA, Sun X, Puffer RC, Deng H, Choy W, Chandra A, Taylor SR, Ferguson AR, Huie JR, Rabinowitz M, Puccio AM, Mukherjee P, Vassar MJ, Wang KKW, Diaz-Arrastia R, Okonkwo DO, Jain S, Manley GT; TRACK-TBI Investigators. Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study. Lancet Neurol. 2019 Oct;18(10):953-961. doi: 10.1016/S1474-4422(19)30282-0. Epub 2019 Aug 23.