Long-term objective: To find intervention therapies that can delay, prevent or reverse the development of type 1 diabetes (T1D).
Specific Aims : 1) BHT-3021 Proinsulin DNA vaccine treatment of recent onset type 1 diabetes subjects Research Design: Preliminary data in animals has shown that using a similar proinsulin DNA vaccine can reverse diabetes in hyperglycemic mice. Pre-clinical studies in mice and non-human primates have found no toxicity for this therapy and have suggested a dosing scheme which could be effective in human subjects with T1D. An ongoing phase 1 study has confirmed the safety of this treatment and has suggested potential efficacy in type 1 diabetes subjects >3 months from diagnosis who still have C-peptide present. The current trial will test 2 doses, 1 and 3 mg, given weekly for 12 doses in a new onset patient population. It will use established measures to determine the effect on C-peptide, HbA1c, total insulin use and other safety parameters. Mechanistic studies to look at effects on insulin and other autoantibodies, T cells and other immune effects will be performed to better understand the potential mechanism of effect. 2) Renewal of TrialNet Center Research Design: The Barbara Davis Center has been at the forefront of defining populations at risk for T1D and other autoimmune diseases and in recruiting patients for the TrialNet Natural History study as well as other TrialNet studies. The BDC TrialNet Center has helped to develop two of the first protocols, TN02 (MMF and DZB in new onset T1D), and TN06 (Nutritional Intervention to Prevent [NIP] Diabetes). Our proposal for renewal outlines our past efforts, current approaches and future goals to not only maintain our current level of productivity, but to increase productivity over the next funding cycle.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Study Section
Special Emphasis Panel (ZDK1-GRB-R (O1))
Program Officer
Leschek, Ellen W
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University of Colorado Denver
Schools of Medicine
United States
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Sanda, Srinath; Type 1 Diabetes TrialNet Study Group (2018) Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests. Pediatr Diabetes 19:271-276
Yeo, Lorraine; Woodwyk, Alyssa; Sood, Sanjana et al. (2018) Autoreactive T effector memory differentiation mirrors ? cell function in type 1 diabetes. J Clin Invest 128:3460-3474
Redondo, Maria J; Geyer, Susan; Steck, Andrea K et al. (2018) A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk. Diabetes Care 41:1887-1894
Greenbaum, Carla J; Speake, Cate; Krischer, Jeffrey et al. (2018) Strength in Numbers: Opportunities for Enhancing the Development of Effective Treatments for Type 1 Diabetes-The TrialNet Experience. Diabetes 67:1216-1225
Smith, Mia J; Rihanek, Marynette; Wasserfall, Clive et al. (2018) Loss of B-Cell Anergy in Type 1 Diabetes Is Associated With High-Risk HLA and Non-HLA Disease Susceptibility Alleles. Diabetes 67:697-703
Gavin, Patrick G; Mullaney, Jane A; Loo, Dorothy et al. (2018) Intestinal Metaproteomics Reveals Host-Microbiota Interactions in Subjects at Risk for Type 1 Diabetes. Diabetes Care 41:2178-2186
Haller, Michael J; Schatz, Desmond A; Skyler, Jay S et al. (2018) Low-Dose Anti-Thymocyte Globulin (ATG) Preserves ?-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes. Diabetes Care 41:1917-1925
Redondo, Maria J; Geyer, Susan; Steck, Andrea K et al. (2018) TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes. Diabetes Care 41:311-317
Sosenko, Jay M; Geyer, Susan; Skyler, Jay S et al. (2018) The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1. Pediatr Diabetes 19:403-409
Michels, Aaron W; Gottlieb, Peter A (2018) Learning From Past Failures of Oral Insulin Trials. Diabetes 67:1211-1215

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