The goal of this proposal is to have the University of California at San Francisco (UCSF) continue as a TrialNet Clinical Center, with the ultimate long-term objectives to better understand the natural history and pathogenesis of type 1 diabetes mellitus (T1D), and to develop therapies to delay or prevent the onset of T1DM in those at risk, and to preserve remnant beta cell function in those with new onset T1D. UCSF is uniquely positioned to serve as a Clinical Center for TrialNet, given a well renowned clinical diabetes program;a large population base for subject recruitment;and a strong established track record with basic, translational, and clinical research on autoimmune interventions for T1D. In addition, the center has Clinical and Translational Science Institute (CTSI) funding, with both a Pediatric and General Clinical Research Center (PCRC, GCRC), and highly regarded investigators with extensive experience in both basic science and clinical research. We have made significant contributions to the TrialNet community on many different levels. We have greatly expanded our network and screening activities over the past 5 years, moving from 4 to the present 20 affiliates, with commensurate increase in enrollment of """"""""at risk"""""""" subjects into monitoring and prevention trials. Specifically, the study goals are:
Specific Aim 1 : To optimize screening for the pathway to prevention protocol, and enroll """"""""at risk"""""""" subjects into the monitoring phase of the protocol. To that end, we will maintain existing affiliates and partnerships while attempting to develop new partners. We will recruit, enroll, and retain at risk subjects within the Pathway to Prevention Study.
Specific Aim 2 : To screen and enroll eligible subjects into existing TrialNet prevention studies, and develop novel approaches to T1DM prevention.
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease in which insulin producing beta cells are completely destroyed by autoreactive T-cells, resulting in dependence on exogenous insulin for life. Current management of T1DM is not optimal, with risk for recurrent hypoglycemia and long term complications. The goal in this proposal is to continue the long-standing role of the University of California at San Francisco (UCSF) as a Clinical Center for the TrialNet network. Together with a network of affiliates, we will screen relatives of those with T1DM, identify a subset at risk, and enroll them into further o-going monitoring, or into prevention trials. The long term goals of the network are to better understand what causes T1DM, optimize our screening and predictive algorithms, and find safe and effective means to delay or prevent the onset of T1DM in those found to be at risk.
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|Chamberlain, Nicolas; Massad, Christopher; Oe, Tyler et al. (2016) Rituximab does not reset defective early B cell tolerance checkpoints. J Clin Invest 126:282-7|
|Sims, Emily K; Chaudhry, Zunaira; Watkins, Renecia et al. (2016) Elevations in the Fasting Serum Proinsulin-to-C-Peptide Ratio Precede the Onset of Type 1 Diabetes. Diabetes Care 39:1519-26|
|Cabrera, Susanne M; Wang, Xujing; Chen, Yi-Guang et al. (2016) Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset. Eur J Immunol 46:1030-46|
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