The Regents of the University of Colorado, Denver

Date of Award

08.24.2009

Program

Type 1 Diabetes, Prevent & Delay

Amount

$153,870

Term of Grant

36 months

Project Title

Reversing Type 1 Diabetes After It Is Established - Supporting Trial Site

Project Description

This proposal seeks funding for two staff members, the site PI and Study Coordinator, to oversee and manage the clinical trial at the Supporting Trial Center. The trial will explore the therapeutic potential of two currently FDA approved drugs through combination therapy for established T1D patients. The project will utilize the expertise of the University of Colorado Denver’s Diabetes Center investigator and staff, who have experience managing multi-center trials. In addition, Dr. Gottlieb and the Center have a strong interest in C-peptide positive patients as candidates for immune intervention trials. The other collaborating Supporting Trial Site will be led by Dr. Stephen Gitelman at the University of Colorado, who is currently investigating Thymoglobulin (an immune suppressive therapy that is widely used in kidney transplants) monotherapy for the reversal of T1D in recent onset T1D patients, and has a strong interest in C-peptide positive patients as candidates for immune intervention trials, and the Master Site will be led by Dr. Mark Atkinson at the University of Florida, whose staff is currently investigating Neulasta (a white blood cell booster that supports natural defenses and helps reduce the risk of infection in patients receiving chemotherapy). This coordinating site was chosen because of its experience with the performance of T1D intervention trials and because its PI is a member of TrialNet and the ImmuneTolerenceNetwork. Each center has within its patient population, over 1,000 diagnosed type 1 diabetics. Proposals for the Master Center at the University of Florida and the other Supporting Trial Center at the University of California San Francisco will be submitted separately. The goal is to test Thymoglobulin and Neulasta in randomized combination therapy in 25 individuals with T1D in an attempt to allow for continued or improved C-peptide production (a marker of the body’s ability to produce insulin), which is an indicator for natural insulin production. As secondary goals, the project will be monitoring immunologic changes that will highlight positive results as well as develop specific tests for these results. Patients will receive Thymoglobulin on two consecutive days, and will then receive Neulasta every 2 weeks for 12 weeks. All subjects will be followed for at least 2 years with the primary statistical endpoint being collected at the end of the year one visit. Subjects with detectable levels of C-peptide at 2 years will be asked to continue to be followed for another 2 years. The overall goal of the project is to focus on research efforts that will define new ways to attenuate autoimmunity to the degree of averting destruction of the insulin producing cells, one’s own, or transplanted cells. This research will provide important data not only for the Helmsley T1D Program but its findings will impact all efforts seeking to cure T1D. Dr. Peter Gottlieb, the site principal investigator for this project, is an Associate Professor of Pediatrics and Medicine at the University of Colorado Denver School of Medicine. He has been the Center Director for Type 1 Diabetes TrialNet at the University of Colorado Denver and the Clinical Director of the Autoimmunity Center of Excellence (ACE) site at the University of Colorado at Denver and is the Director of the Translational Research Unit at the Barbara Davis Center. He is an adult endocrinologist who has focused his research work in the immunology of diabetes in mouse and human models of T1D. Dr. Gottlieb also has extensive experience with multicenter clinical trials and has been the study PI for the first intervention study run by TrialNet to treat new onset type 1 diabetes and similar studies for newly diagnosed type I patients.