U54NS121688

Endophenotypes of Persistent Post-Concussive Symptoms in Adolescents: CARE4KIDS - Project Summary/Abstract – Overall, the prediction, detection, management, and prevention of persistent post-concussive symptoms (PPCS) represent some of the most important neurological challenges in the science of traumatic brain injury (TBI) today. For the purposes of this application, PPCS will refer to post-concussive symptoms lasting three months or longer, consistent with the National Institute of Neurological Disorders and Stroke Common Data Elements for concussion.

We approach this using the concept of endophenotypes, quantitative behavioral traits characterized by objective measures using blood-based, imaging, or autonomic measures or other techniques. Understanding the endophenotypes of PPCS will provide opportunities for early identification and potentially for intervention, treatment, and prevention. The overarching goal of this application is to develop a predictive algorithm for PPCS endophenotypes in early and middle adolescents (EMA) to inform clinical screening, management, and future research.

Our specific aims are:

Specific Aim 1: In a development cohort, develop and characterize individual objective biomarkers predictive of PPCS by combining biomarkers with symptom clusters and neuropsychological function. Biomarkers will be examined in three research cores: autonomic, imaging, and blood-based.

Specific Aim 2: To develop and characterize endophenotypes of PPCS in EMA by combining two or more objective biomarkers with symptom clusters and neuropsychological measures.

Specific Aim 3: To prospectively validate endophenotype biomarkers from Aims 1 and 2 in a broad group of EMA with concussion (validation cohort).

Specific Aim 4: To create a clinically useful risk stratification algorithm using validated biomarkers, in conjunction with symptoms and neurobehavioral function, which will predict the development of PPCS.

The development cohort will be recruited from existing concussion and sports medicine clinics at six sites within the Four Corners Youth Consortium (4CYC). This cohort will include subjects presenting from 0-12 months after concussion, will likely be enriched in those with PPCS, and has proven feasible for recruitment into an observational prospective registry.

The validation cohort will be recruited from the same clinics but also expanded to primary care clinics/networks and emergency departments (acutely/subacutely) and followed to a chronic time point. With this broader and more generalizable cohort, the candidate blood-based, imaging, and autonomic biomarkers from the development cohort will be tested and validated. It is from these second cohort data that a predictive algorithm (likely combining clinical and biomarker measures) will be developed.

Los Angeles University Of California

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Los Angeles, California 900950001 United States

Single Zip Code

Biological Measures for Prognosing and Monitoring of Persistent Concussive Symptoms in Early and Middle Adolescents: Center Without Walls (PCS-EMA CWOW) (U54 Clinical Trial Not Allowed) (RFA-NS-20-016)

Amendment Since initial award the End Date has been extended from 08/31/26 to 03/31/27 and the total obligations have increased 274% from $3,344,994 to $12,522,070.