- A Platform Trial Design to Accelerate Translational Therapies in a Canine Disease Model of ALS
- Accelerate Cellular Immunotherapy Development for Treatment of Life-Threatening Childhood Disorders
- Effects of apoE-Enhancing Compounds on Alzheimer’s Disease Phenotypes In Vivo
- Harnessing Human Brain and Liver Microphysiological Systems for Testing Therapeutics for Metastatic Melanoma
- Harnessing the Power of CTSA-CDRN Data Networks: Using Social Determinants of Health, Frailty and Functional Status to Identify At-Risk Patients and Improve Risk Adjustment
- Impact of Breast Milk on Infant Gut Microbiome
- Increasing Access to Clinical Microbiome Specimens via a Living µBiome Bank
- Peer-based Retention Of people who Use Drugs in Rural Research (PROUD-R2)
- Precision Medicine in the Diagnosis of Genetic Disorders in Neonates
- TCR and BCR Deep Sequencing to Distinguish Autoimmune Recurrence from Allograft Rejection
- TEAMSS – Transforming Expanded Access to Maximize Support & Study
- Transforming Exercise Testing and Physical Activity Assessment in Children: New Approaches to Advance Clinical Translational Research in Child Health
University of Missouri
Principal Investigator: Joan Ripley Coates, D.V.M., M.S., and Sarah A. Moore, D.V.M.
Grant Number: 1-R21TR002277-01A1
Collaborating Institutions: The Ohio State University, Tufts University, North Carolina State University, Voyager Therapeutics
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease in people. Despite best efforts, nearly all trials of new therapies have failed to improve outcomes. This project will leverage spontaneous degenerative myelopathy (DM) in dogs, a relevant model of human ALS, to interrogate and optimize a novel therapeutic approach, with the ultimate goal of markedly improving translational efficiency.
Seattle Children’s Hospital
Principal Investigator: Julie R. Park, M.D., and Bonnie W. Ramsey, M.D.
Grant Number: 1-U01TR002487-01
Collaborating Institutions: Children’s National Health System, UCSF Benioff Children’s Hospital, Children’s Hospital Los Angeles, University of Colorado Denver, Fred Hutchinson Cancer Research Center
Cellular immunotherapies are emerging as a paradigm-shifting, personal and precise treatment for a range of fatal rare diseases in children. Early Phase I trials in refractory leukemia have provided proof of concept that this approach can be lifesaving. We propose to establish a consortium of pediatric hospitals affiliated with Clinical and Translational Science Awards (CTSA) Program hubs proposed in this application, called the Consortium for Pediatric Cellular Immunotherapy, to accelerate production and delivery of these novel lifesaving therapies to children.
Principal Investigators: Tae-Wan Kim, Ph.D., and John R. Cirrito, Ph.D.
Grant Number: 1-R21TR002029-01A1
Collaborating Institution: Washington University in St. Louis
Increasing brain levels of apolipoprotein E (apoE) is an attractive therapeutic strategy for treating Alzheimer’s disease (AD). The goal of this proposal is to determine whether pharmacological elevation of apoE levels can alleviate AD neuropathogenesis in mouse models of AD. Successful completion of our proposed studies will lead to the identification of compounds that are suitable for mechanistic study and drug discovery for AD.
Harnessing Human Brain and Liver Microphysiological Systems for Testing Therapeutics for Metastatic Melanoma
Principal Investigator: John Peter Wikswo, Ph.D., M.S., William L. Murphy, Ph.D., M.S., and D. Lansing Taylor, Ph.D.
Grant Number: 1-U01TR002383-01
Collaborating Institutions: University of Wisconsin–Madison, University of Pittsburgh School of Medicine, AstraZeneca
This clinical study is designed to compare the outcome from drugs chosen and not chosen by the treating physician (i.e., the patient’s own response to therapy can be measured against the drug response predicted by microphysiological system models). Successful translation of these models from the laboratory to the clinic would improve in vitro prediction of the response of patient-specific tumors. This would have a near-term impact in clinical trials of investigatory drugs and ultimately could guide the selection of optimal therapies for each patient.
Harnessing the Power of CTSA-CDRN Data Networks: Using Social Determinants of Health, Frailty and Functional Status to Identify At-Risk Patients and Improve Risk Adjustment
University of Texas Health Science Center at San Antonio
Principal Investigator: Paula K. Shireman, M.D., M.S.
Grant Number: 1-U01TR002393-01
Collaborating Institutions: University of Texas at Austin, University of Texas Health Science Center at Houston, University of Pittsburgh
Social risk factors, including poverty, being a minority, lack of an education, and frailty, are all associated with having worse health outcomes and with more difficulties recovering after surgical procedures. Safety net hospitals take care of many people with social risk factors and are being judged on the quality of care provided without accounting for the challenges faced by poor people. We will study the effect of social risk factors and frailty on health outcomes after surgery to identify patients who would benefit from care pathways that help poor and/or frail people.
University of Rochester
Principal Investigator: Kirsi Järvinen-Seppo, M.D., Ph.D., and R. John Looney, M.D.
Grant Number: 1-R21TR002516-01
Collaborating Institutions: University of California, San Diego, Icahn School of Medicine at Mount Sinai
The gut microbiome plays a critical role in the development of the immune system, and breastfeeding is a major factor affecting infant gut microbiome composition. However, breast milk composition differs between mothers. This study will provide critical new knowledge about the impact of breast milk composition on the development of the infant gut microbiome. Research conducted in this project is used to establish maternal interventions to modify breast milk composition to favor protection against allergic and noncommunicable inflammatory diseases.
Medical University of South Carolina
Principal Investigator: Alexander V. Alekseyenko, Ph.D.
Grant Number: 1-R21TR002513-01
Collaborating Institutions: University of Iowa, The George Washington University
The clinical enterprises generate volumes of specimens suitable for translational research, yet those are not used to their full potential. At the same time, traditional microbiology biobanking is expensive, limiting many health care organizations from having a viable biobanking solution. By leveraging widely adopted commercial electronic health record capabilities, the Living µBiome Biobank will redefine how recruitment and specimen collection is performed, by allowing for just-in-time capture of existing microbiome specimens and making them available for translational research across CTSA Program hubs.
Oregon Health & Science University
Principal Investigator: Philip Todd Korthuis, M.D., M.P.H., and April Marie Young, Ph.D., M.P.H.
Grant Number: 1-U01TR002631-01
Collaborating Institutions: University of Kentucky Research Foundation, Emory University, University of North Carolina at Chapel Hill, The Ohio State University
Optimal strategies for recruiting and retaining people with opioid use disorder in clinical research in rural America remain unknown. The Peer-based Retention Of people who Use Drugs in Rural Research (PROUD-R2) study leverages the national rural opioid initiative infrastructure, with sites in rural Oregon and Appalachian Kentucky and Ohio, and partnerships with three Clinical and Translational Science Award sites and the National Institute on Drug Abuse (NIDA) Clinical Trials Network to test an innovative peer-based strategy to improve research participation and retention of people who use drugs in rural communities.
Tufts Medical Center
Principal Investigator: Jonathan M. Davis, M.D., and Jill Lamanna Maron, M.D., M.P.H.
Grant Number: 1-U01TR002271-01
Collaborating Institutions: Rady Children’s Institute for Genomic Medicine, University of North Carolina at Chapel Hill, Columbia University, Icahn School of Medicine at Mount Sinai, UPMC Children’s Hospital of Pittsburgh, University of Michigan
Directed application of a rapid targeted next-generation sequencing (TNGS) technology to augment traditional clinical and diagnostic testing should improve our ability to detect underlying genetic causes and improve outcomes in our highest risk neonates. We will (1) perform a prospective study of the impact of TNGS on time to molecular diagnosis and the accuracy of this diagnosis in symptomatic neonates in the neonatal intensive care unit (NICU); (2) evaluate lengths of hospital stay and total hospital costs for high-risk neonates admitted to the NICU; (3) determine the time from initial diagnosis to initiation of an appropriate therapy, enrollment in a clinical trial or initiation of palliative care; and (4) integrate a user-friendly, electronic mechanism for accelerated TNGS result return and re-review.
Columbia University Health Sciences
Principal Investigator: Megan Sykes, M.D.
Grant Number: 1-R21TR002279-01
Collaborating Institution: University of Pennsylvania
This project will attempt to distinguish rejection from recurrent autoimmune liver disease after liver transplantation by using a sequencing approach to identify and track the B- and T-cell clones that cause autoimmunity and rejection. We will thereby better understand the interplay between alloimmune and autoimmune responses causing liver transplants to fail and ultimately provide better treatment to patients needing transplants for these diseases. Success of this approach will be applicable to autoimmune diseases of other organs as well, including the kidneys, heart and lungs.
University of Michigan at Ann Arbor
Principal Investigator: George Alexander Mashour, M.D., and Kevin J. Weatherwax
Grant Number: 1-U01TR002488-01
Collaborating Institutions: University of Rochester, University of Texas Southwestern Medical Center, Duke University
TEAMSS (Transforming Expanded Access to Maximize Support and Study) seeks to advance clinical care and translational research by improving patient access to experimental therapies through a federated, national consortium for expanded access interventions. Expanded access provides an opportunity for patients who either lack therapeutic options or are ineligible for clinical trials to potentially benefit from the clinical use of experimental drugs, biologics and medical devices. By developing this national consortium, we will build a positive impact by, for the first time, creating a foundation for an integrated, nationwide approach to expanded access that can improve care for the most vulnerable patients.
Transforming Exercise Testing and Physical Activity Assessment in Children: New Approaches to Advance Clinical Translational Research in Child Health
University of California, Irvine
Principal Investigator: Dan M. Cooper, M.D., and Shlomit Radom-Aizik, Ph.D.
Grant Number: 1-U01TR002004-01A1
Collaborating Institutions: Ann & Robert H. Lurie Children’s Hospital of Chicago, Children’s Hospital Los Angeles
Despite the critical role played by physical activity in growth and disease prevention across the lifespan, exercise testing and physical activity assessments have failed to achieve their potential in clinical research or practice. In this project, three CTSA Program sites and two national organizations will work together to study novel approaches to laboratory exercise testing in healthy children and in challenging health conditions. The test results will be linked to metrics of habitual physical activity, inflammation and exercise-responsive gene signals. A toolkit of innovative metrics for exercise testing that can transform clinical research and practice focused on exercise and its impact on children will be made available.
Vanderbilt University Medical Center*
Principal Investigator: David M. Aronoff, M.D.
Grant Number: 5U01TR002398-02
Collaborating Institutions: Washington University in St. Louis; The University of North Carolina at Chapel Hill
Clostridium difficile infection (CDI) is a leading nosocomial infection and the primary identifiable cause of antibiotic-associated diarrhea. Recurrent CDI (rCDI) complicates 20 to 30 percent of primary episodes of disease and is associated with an increased risk of death and poor quality of life. Evidence from epidemiological and animal studies suggests that the U.S. Food and Drug Administration–approved drug misoprostol (a prostaglandin analog) may prevent rCDI. This project will use a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of misoprostol in the prevention of first recurrence of CDI in adults age 50 and older. Three aims are proposed:
- Determine whether misoprostol modifies the rate and severity of rCDI during the first 8 weeks after standard vancomycin therapy.
- Determine the effect of misoprostol on the gut microbiome, diarrhea occurrence and severity, and the development of C. difficile antitoxin antibodies.
- Continue the clinical development of misoprostol to optimize its potential to impact clinical practice and rapidly affect human health.
* Note: This U01 was funded by Drug Development Partnership Programs, Office of the Director, National Center for Advancing Translational Sciences.