- Translational Research Workforce Training: Leveraging the Veterinary Specialist
- Genetic and Functional Dissection of Congenital Anomalies of the Brain
- SPROUT–CTSA Collaborative Telehealth Research Network
- ICT Tools for Rare Diseases
- Repurposing Pharmacological Agents for Inherited Mast Cell Disorders of the Gut
- Unintended Prolonged Opioid Use
- Instrumenting the Delivery System for a Genomics Research Information Commons
- Enhancing Infrastructure for Clinical and Translational Research to Address the Opioid Epidemic
- Coordinated Medical Treatment of Opioid Use Disorder and Infectious Disease
University of Wisconsin–Madison
Principal Investigator: Lauren A. Trepanier, D.V.M., Ph.D.
Grant Number: 1-U01TR002953-01
Collaborating Institutions: University of California, Davis; University of Minnesota; University of Florida
Advances in human health rely on valid animal models of disease. Rodent models can answer important questions about disease pathogenesis and test promising therapies, but sometimes fail to predict disease responses seen in humans. Naturally occurring (spontaneous) diseases in companion animals—such as epilepsy, glaucoma, or hemophilia—can advance our understanding of similar diseases in human patients. This project will support the professional development of veterinary specialists with expertise in these animal diseases to become clinician-scientists who can be productive contributors to interdisciplinary research teams that can address human health problems from multiple perspectives.
The University of North Carolina at Chapel Hill
Principal Investigator: Neeta L. Vora, M.D.
Grant Number: 1-R21TR002770-01
Collaborating Institution: Duke University
Human brain development remains an incompletely understood process, yet congenital brain abnormalities affect approximately three in 1,000 pregnancies and more than 2,000 newborns annually in the United States. Diagnostic tools—such as fetal magnetic resonance imaging, prenatal ultrasound and prenatal gene sequencing—are capable of increasing our understanding of the human brain. By intersecting human prenatal gene sequencing in pregnancies affected by congenital brain abnormalities, bioinformatics filters to identify novel candidate genes, and functional modeling in zebrafish, we aim to develop a workflow that can be adapted broadly across organ systems to investigate of novel candidate genes.
Medical University of South Carolina
Principal Investigator: Steven D. McSwain, M.D.
Grant Number: 1-U01TR002626-01
Collaborating Institutions: Children’s Hospital of Philadelphia, Mercy Health, American Academy of Pediatrics, University of Colorado Denver
Because of the rapid evolution of telehealth and the resulting variety and complexity of different telehealth practices across the country, conducting quality research into the impact of telehealth services on health care costs, quality and access historically has been a challenge. The SPROUT (Supporting Pediatric Research on Outcomes and Utilization of Telehealth) Collaborative was established in collaboration with the American Academy of Pediatrics to rigorously evaluate pediatric telehealth services. The SPROUT–Clinical and Translational Science Award (CTSA) Collaborative Telehealth Research Network will enhance the existing infrastructure and expertise of SPROUT with the established research resources of the national CTSA Consortium to develop, iteratively test and enhance, and disseminate an innovative model for clinical and translational telehealth research.
Research Triangle Institute
Principal Investigator: Ty A. Ridenour, Ph.D.
Grant Number: 1-R21TR002402-01A1
Collaborating Institution: Harvard University
Treatment efficacy and effectiveness studies nearly always use randomized controlled trials, which require large samples and funding pools and are therefore not feasible for numerous rare diseases. This R21 proposal for an NCATS Exploratory CTSA Collaborative Innovation Award is to create tools to assist researchers of rare diseases in conducting idiographic clinical trials (ICTs), which use subject-as-own-control experimental designs, time series data and hierarchical modeling that is tailored for small samples, including N=1. This approach to conducting clinical trials requires far fewer resources than randomized controlled trials; enables rigorous small-sample clinical trials; and allows efficacy testing for rare diseases, hard-to-reach locales and underrepresented peoples.
University of Pittsburgh
Principal Investigator: Yelizaveta Konnikova, M.D., Ph.D.
Grant Number: 1-R21TR002639-01A1
Collaborating Institutions: University of Florida, Harvard University, The University of New Mexico
In this study, mast cells (MC) from patients with hereditary alpha tryptasemia (HAT), a disorder in which multiple copies of the TPSAB1 gene correlate with elevated serum tryptase, are used to study the effect of MC phenotype and function on the chronic inflammatory effects in the gut. This knowledge will be utilized to develop new therapeutic uses for existing drugs that target MC functional pathways. The purpose of this multicenter Clinical and Translational Sciences Institute supplement is to use current state-of-the-art techniques to explain differences in functional MC and inflammatory gut tissue in patients with HAT compared with MC in control patients (patients with inflammatory bowel disease in remission and systemic mastocytosis patients).
Mayo Clinic, Rochester
Principal Investigator: W. Michael Hooten, M.D.
Grant Number: 1-U01TR002743-01
Collaborating Institutions: University of Minnesota, University of Michigan, Yale University
Intentional short-term opioid use is emerging as a previously underrecognized segue to unintended prolonged opioid use (UPOU). Clinical strategies aimed at preventing UPOU in health care settings are lacking, due in part to an absence of information about how this poorly understood clinical phenomenon develops. A recently developed conceptual framework to explain UPOU includes patient characteristics, practice environment characteristics and opioid prescriber characteristics that interact to either facilitate or impede UPOU. In this application, four CTSA hubs will explore the potential of a secure mobile personal health platform to identify incident cases of UPOU and to prospectively recruit patients and opioid prescribers for assessments that will be used to evaluate the conceptual framework of UPOU.
Boston Children’s Hospital
Principal Investigator: Kenneth L. Mandl, M.D.
Grant Number: 1-U01TR002623-01A1
Collaborating Institutions: Harvard University, Children’s Hospital of Philadelphia, Cincinnati Children’s Hospital, University of Pittsburgh, Washington University in St. Louis
A patient’s genetic variant must be contextualized against a population-based reference and detailed phenotype to assess its pathogenicity and impact on prognosis, based on the care trajectories and outcomes of other patients with the variant, or similar variants, of a particular gene. However, CTSA researchers do not have ready access to a definitive and representative reference dataset linking the genome to diagnosis, clinical progression, therapeutic response and precision-adjusted laboratory reference ranges. We will facilitate a CTSA-wide, federated Genomics Information Commons, underpinned by coordinated, local, broadly consented biobanking initiatives. The goal is rapid identification and analysis of representative cohorts, made possible by a federated information technology infrastructure, with advanced phenotype and genotype query capability.
Medical University of South Carolina
Principal Investigator: Leslie A. Lenert, M.D.
Grant Number: 1-U01TR002628-01A1
Collaborating Institutions: University of California, San Diego; University of Kentucky; Dartmouth College
Patients presenting with opioid-related overdose to hospital emergency departments represent a high-risk group for morbidity and mortality and a potential target for interventions to combat the opioid epidemic. This proposal aims to develop a feasible and effective interinstitutional research database and network focused on these patients. These tools will inform point-of-care service delivery, as well as enhance nationwide prevention and treatment interventions.
Principal Investigator: Sandra Ann Springer, M.D.
Grant Number: 1-U01TR002763-01
Collaborating Institutions: Columbia University, Medical University of South Carolina
Opioid use disorders (OUD) have significantly increased in the United States and are associated with a rise in invasive bacterial infections and new epidemics of HIV and hepatitis C virus. Infectious disease (ID) specialists and hospitalists are a critical and logical resource to build capacity and increase access to medication treatment for this population of patients with OUD and infections. We will conduct a randomized controlled trial of a new model of care in which OUD is managed by ID specialists and hospitalists, concurrent with management of the OUD-related infections using long-acting injectable buprenorphine, with the hypothesis that this model of care will increase successful referral and transition to community-based outpatient medication treatment for OUD, reducing opioid use and related morbidity.