Traumatic brain injury (TBI) is recognized as a heterogeneous disorder. Analogous to cancer, TBI has multiple phenotypes. To target and treat TBI effectively, one must diagnose and characterize the specific problem(s) of individual patients. Yet there are no high-sensitivity diagnostic tools, no established subgroups, and no precision medicine protocols to enable targeted therapy for TBI patients. Despite decades of research, there are no Food and Drug Administration (FDA)-approved treatments for TBI, and there have been no successful clinical trials in TBI (28 randomized TBI-related clinical trials and zero successes). There is a need for bold new research paradigms to determine the benefits of current and evolving treatments and interventions. A new approach is necessary to achieve the rapid breakthroughs in TBI necessary to address this major defense and public health need, identify the most valuable interventions, and improve outcome after TBI.
Objectives: TEAM-TBI (Targeted Evaluation, Action, and Monitoring of Traumatic Brain Injury) is a research clinical trial that brings together TBI patients, advanced evaluation methods, and world-class experts in a monitored, multiple interventional trial design to address the heterogeneity of TBI and identify evidence-based treatment protocols. The goal is to confirm efficacious targeted therapies for TBI and provide deployable protocols and technology for large-scale cost-effective diagnosis and management. TEAM-TBI proposes a new approach to clinical trials in TBI that will evolve transformative diagnostic technology and treatment, improve metrics and provide rigorous tests of combinatorial interventions, and lower cost and speed for delivery of effective, deployable treatments.
Specific Aims: This proposal has three aims. (1) Develop and test a comprehensive intake evaluation for TBI subjects that will delineate clinical trajectories, parse out the heterogeneity of the disorder, and empower targeted therapy. (2) Develop and deploy telemonitoring and telemedicine modalities that will enable ongoing assessment and feedback of TBI subjects during remote treatment phase. (3) Test the comparative effectiveness of targeted therapies based on the identified subtypes for individual TBI subjects via a combination of rehabilitative, pharmacologic, nutriceutical, and electriceutical interventions.
Study Design: The TEAM-TBI program pilot will recruit 360 patients in small groups of 12 over a 2-year period (includes follow-up) from three sites: (1) University of Pittsburgh Medical Center; (2) National Intrepid Center of Excellence (NICoE); and (3) Naval Medical Center San Diego (NMCSD). Subjects will undergo a Comprehensive Intake Assessment, advanced neuroimaging, and biomarker analysis. A multidisciplinary group case review will stratify subjects into clinical TBI subtypes; consensus for targeted therapies for individual participants will be derived. Therapeutic options will, in part, be derived from the Department of Defense (DoD) Neurotrauma Pharmacology Workshop Summary and the DoD Cognitive Rehabilitation Consensus Conference. Each participant will then depart with a customized Wounded Warrior Toolkit that will provide participants (and treatment teams) support to better cope with the consequences of their TBI, all necessary materials for targeted therapies, mobile technology to monitor ongoing therapy, and interval contact with TEAM-TBI team members to monitor response to therapy. The TEAM-TBI database will be built off the TBI common data elements and ultimately housed in the FITBIR (Federal Interagency Traumatic Brain Injury Research).
Relevance: TBI has impacted over 360,000 warriors in Operation Iraqi Freedom and Operation Enduring Freedom and will likely exceed half a million before US withdrawals are complete. Current diagnostic procedures have a high miss rate (over 85%) and do not subclassify TBI to provide clinically actionable information for targeted therapies. Furthermore, there are currently no FDA-approved pharmacological therapies for TBI and little consensus regarding effectiveness of cognitive rehabilitation strategies. The TEAM-TBI program pilot represents a new approach to TBI clinical trials to overcome the limitations of past efforts and achieve long-awaited breakthroughs for TBI survivors.