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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Application #
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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Xu, Ping; Krischer, Jeffrey P; Type 1 Diabetes TrialNet Study Group (2016) Prognostic Classification Factors Associated With Development of Multiple Autoantibodies, Dysglycemia, and Type 1 Diabetes-A Recursive Partitioning Analysis. Diabetes Care 39:1036-44
Fouts, Alexandra; Pyle, Laura; Yu, Liping et al. (2016) Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects? Diabetes Care 39:1738-44
Triolo, Taylor M; Maahs, David M; Pyle, Laura et al. (2016) Effects of Frequency of Sensor-Augmented Pump Use on HbA1c and C-Peptide Levels in the First Year of Type 1 Diabetes. Diabetes Care 39:e61-2
Narsale, Aditi; Moya, Rosita; Robertson, Hannah Kathryn et al. (2016) Data on correlations between T cell subset frequencies and length of partial remission in type 1 diabetes. Data Brief 8:1348-51
Bundy, Brian N; Krischer, Jeffrey P; Type 1 Diabetes TrialNet Study Group (2016) A model-based approach to sample size estimation in recent onset type 1 diabetes. Diabetes Metab Res Rev 32:827-834
Pugliese, Alberto; Boulware, David; Yu, Liping et al. (2016) HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 Haplotype Protects Autoantibody-Positive Relatives From Type 1 Diabetes Throughout the Stages of Disease Progression. Diabetes 65:1109-19
Hao, Wei; Gitelman, Steven; DiMeglio, Linda A et al. (2016) Fall in C-Peptide During First 4 Years From Diagnosis of Type 1 Diabetes: Variable Relation to Age, HbA1c, and Insulin Dose. Diabetes Care 39:1664-70
Bingley, Polly J; Boulware, David C; Krischer, Jeffrey P et al. (2016) The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance: development of other autoantibodies and progression to type 1 diabetes. Diabetologia 59:542-9
DiMeglio, Linda A; Cheng, Peiyao; Beck, Roy W et al. (2016) Changes in beta cell function during the proximate post-diagnosis period in persons with type 1 diabetes. Pediatr Diabetes 17:237-43
Moya, Rosita; Robertson, Hannah Kathryn; Payne, Dawson et al. (2016) A pilot study showing associations between frequency of CD4(+) memory cell subsets at diagnosis and duration of partial remission in type 1 diabetes. Clin Immunol 166-167:72-80

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