Transforming Research and Clinical Knowledge in Traumatic Brain Injury

NCT ID: NCT02119182

Last Updated: 2020-09-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

2996 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-03-02

Study Completion Date

2020-08-31

Brief Summary

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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

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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.

Conditions

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Traumatic Brain Injury

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Comprehensive Assessment with MRI

* In-Person Outcome Assessment at 2 weeks, 6 months, and 12 months.
* Phone Outcome Assessment at 3 months.
* 3T Magnetic Resonance Imaging (MRI) at 2 weeks and 6 months.
* Blood Draw for Plasma, DNA, Serum, RNA at baseline, in hospital (if applicable), 2 weeks, and 6 months (DNA at baseline only).

In-Person Outcome Assessment

Intervention Type BEHAVIORAL

NIH Flexible Outcome Assessment Battery Framework Measures In-Person at 2 Weeks, 6 Months, and 12 Months, and by Phone at 3 Months.

3T Magnetic Resonance Imaging (MRI)

Intervention Type PROCEDURE

3T Research MRI at 2 weeks and 6 months.

Blood Draw for Plasma, DNA, Serum, RNA

Intervention Type PROCEDURE

Blood Draw for Plasma, DNA, Serum, RNA at baseline, in hospital (if applicable), 2 weeks, and 6 months (DNA at baseline only).

Comprehensive Assessment without MRI

* In-Person Outcome Assessment at 2 weeks, 6 months, and 12 months.
* Phone Outcome Assessment at 3 months.
* Blood Draw for Plasma, DNA, Serum, RNA at baseline, in hospital (if applicable), 2 weeks, and 6 months (DNA at baseline only).

In-Person Outcome Assessment

Intervention Type BEHAVIORAL

NIH Flexible Outcome Assessment Battery Framework Measures In-Person at 2 Weeks, 6 Months, and 12 Months, and by Phone at 3 Months.

3T Magnetic Resonance Imaging (MRI)

Intervention Type PROCEDURE

3T Research MRI at 2 weeks and 6 months.

Blood Draw for Plasma, DNA, Serum, RNA

Intervention Type PROCEDURE

Blood Draw for Plasma, DNA, Serum, RNA at baseline, in hospital (if applicable), 2 weeks, and 6 months (DNA at baseline only).

Brief Assessment

• Telephone outcome assessment at 2 weeks, 3 months, 6 months, and 12 months.

Phone Outcome Assessment

Intervention Type BEHAVIORAL

NIH Flexible Outcome Assessment Battery Framework Measures by Phone at 2 Weeks, 3 Months, 6 Months, and 12 Months.

Interventions

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In-Person Outcome Assessment

NIH Flexible Outcome Assessment Battery Framework Measures In-Person at 2 Weeks, 6 Months, and 12 Months, and by Phone at 3 Months.

Intervention Type BEHAVIORAL

Phone Outcome Assessment

NIH Flexible Outcome Assessment Battery Framework Measures by Phone at 2 Weeks, 3 Months, 6 Months, and 12 Months.

Intervention Type BEHAVIORAL

3T Magnetic Resonance Imaging (MRI)

3T Research MRI at 2 weeks and 6 months.

Intervention Type PROCEDURE

Blood Draw for Plasma, DNA, Serum, RNA

Blood Draw for Plasma, DNA, Serum, RNA at baseline, in hospital (if applicable), 2 weeks, and 6 months (DNA at baseline only).

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

1 Year

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Department of Health and Human Services

FED

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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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, MD, PhD

Role: STUDY_DIRECTOR

Harvard Medical School, Spaulding Rehabilitation Hospital

Ann-Christine Duhaime, MD

Role: PRINCIPAL_INVESTIGATOR

Harvard Medical School, Massachusetts General Hospital

Dana P. Goldman, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Arthur W. Toga, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Kevin Smith, MSIS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Opeolu M. Adeoye, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Neeraj Badjatia, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, College Park

Randall M. Chesnut, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Gillian A. Hotz, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Christopher J. Madden, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Randall E. Merchant, PhD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Alex B. Valadka, MD

Role: PRINCIPAL_INVESTIGATOR

Seton Healthcare Family

Andrew I. Maas, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Antwerp University Hospital, Edegem, Belgium

David K. Menon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cambridge, Cambridge, United Kingdom

Isabelle Gagnon, PhD, MS

Role: PRINCIPAL_INVESTIGATOR

McGill University

Murray B Stein, MD, MPH

Role: STUDY_DIRECTOR

University of California, San Diego

Ryan S Kitagawa, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

David M Schnyer, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas - Austin

Vincent Y Wang, MD, PhD, MBA

Role: PRINCIPAL_INVESTIGATOR

Dell Seton Medical Center

David W Wright, MD, FACEP

Role: PRINCIPAL_INVESTIGATOR

Emory University

Michael McCrea, PhD, ABPP

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Gregory Hawryluk, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Richard B Rodgers, MD, FAANS

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Uzma Samadani, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota/Hennepin County Medical Center

Mitchell Cohen, MD

Role: PRINCIPAL_INVESTIGATOR

Denver Health and Hospital Authority

Cindy Harrison-Felix, PhD, FACRM

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver/Craig Hospital

Roland Torres, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

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University of California, San Francisco

San Francisco, California, United States

Site Status

Denver Health and Hospitals Authority

Denver, Colorado, United States

Site Status

University of Colorado/Craig Hospital

Englewood, Colorado, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

University of Maryland

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Spaulding Rehabilitation Hospital

Charlestown, Massachusetts, United States

Site Status

University of Minnesota/Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

University of Pennsylvania/Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Dell Seton Medical Center

Austin, Texas, United States

Site Status

University of Texas at Austin

Austin, Texas, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

TIRR Memorial Hermann

Houston, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Yue JK, Kanter JH, Barber JK, Huang MC, van Essen TA, Elguindy MM, Foreman B, Korley FK, Belton PJ, Pisica D, Lee YM, Kitagawa RS, Vassar MJ, Sun X, Satris GG, Wong JC, Ferguson AR, Huie JR, Wang KKW, Deng H, Wang VY, Bodien YG, Taylor SR, Madhok DY, McCrea MA, Ngwenya LB, DiGiorgio AM, Tarapore PE, Stein MB, Puccio AM, Giacino JT, Diaz-Arrastia R, Lingsma HF, Mukherjee P, Yuh EL, Robertson CS, Menon DK, Maas AIR, Markowitz AJ, Jain S, Okonkwo DO, Temkin NR, Manley GT; TRACK-TBI Investigators. Clinical profile of patients with acute traumatic brain injury undergoing cranial surgery in the United States: report from the 18-centre TRACK-TBI cohort study. Lancet Reg Health Am. 2024 Oct 17;39:100915. doi: 10.1016/j.lana.2024.100915. eCollection 2024 Nov.

Reference Type DERIVED
PMID: 39497836 (View on PubMed)

Yue JK, Etemad LL, Elguindy MM, van Essen TA, Belton PJ, Nelson LD, McCrea MA, Vreeburg RJG, Gotthardt CJ, Tracey JX, Coskun BC, Krishnan N, Halabi C, Eagle SR, Korley FK, Robertson CS, Duhaime AC, Satris GG, Tarapore PE, Huang MC, Madhok DY, Giacino JT, Mukherjee P, Yuh EL, Valadka AB, Puccio AM, Okonkwo DO, Sun X, Jain S, Manley GT, DiGiorgio AM; TRACK-TBI Investigators; Badjatia N, Barber J, Bodien YG, Fabian B, Ferguson AR, Foreman B, Gardner RC, Gopinath S, Grandhi R, Russell Huie J, Dirk Keene C, Lingsma HF, MacDonald CL, Markowitz AJ, Merchant R, Ngwenya LB, Rodgers RB, Schneider ALC, Schnyer DM, Taylor SR, Temkin NR, Torres-Espin A, Vassar MJ, Wang KKW, Wong JC, Zafonte RD. Prior traumatic brain injury is a risk factor for in-hospital mortality in moderate to severe traumatic brain injury: a TRACK-TBI cohort study. Trauma Surg Acute Care Open. 2024 Jul 24;9(1):e001501. doi: 10.1136/tsaco-2024-001501. eCollection 2024.

Reference Type DERIVED
PMID: 39081460 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35963263 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35065038 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32769835 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31451409 (View on PubMed)

Related Links

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Other Identifiers

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1U01NS086090-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1U01NS086090-01

Identifier Type: NIH

Identifier Source: org_study_id

View Link

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