The long-term objective of this proposal is the prevention of autoimmune mediated Type 1 diabetes mellitus (T1D). Many promising interventions must be tested in a safe and efficient manner in order to achieve this goal. A well-organized cooperative network of capable institutes, Type 1 Diabetes TrialNet, has greatly facilitated the prompt completion of many clinical trials needed to test these potential interventions. The application responds to the RFA to select the clinical centers that will form TrialNet for the next 3 to 5 years. The first goal of this proposal is to both continue and improve the infrastructure essential to completing the current TrialNet studies seeking to prevent T1D in subjects at risk for T1D and to preserve endogenous insulin secretion in subjects with new onset T1D. This section of the proposal reviews Stanford's seven-year experience as a TrialNet national center in central California. The proposal highlights Stanford's plans for extending and improving recruitment and retention activities for the next 3 to 5 years. These plans include both completing the current TrialNet studies and implementing the expected upcoming trials. Stanford is particularly excited about the soon to start TrialNet protocol, developed by Stanford, to test the glucose sensor enhanced strict glycemic control in subjects with new onset T1D. The second goal proposes a clinical study to develop and test a novel intervention using modified autologous dendritic cell therapy to preserve endogenous insulin secretion in subjects with new onset T1D in a multicenter TrialNet study. The proposal, Transgenic IL-4 expression by autologous dendritic cells in new onset Type 1 diabetes (aDC/IL-4), articulates Stanford's approach to testing this therapy in a collaborative manner with other centers in TrialNet. Studies using dendritic cells therapeutically have demonstrated no significant adverse events, so that it is now reasonable to consider this innovative approach as a possible therapy for diabetes prevention. This proposal describes both Phase 1 safety studies followed by Phase 2 efficacy studies using aDC/IL-4. Ultimately, this therapy will likely have a role in preventing T1D

Public Health Relevance

Type 1 diabetes mellitus is a serious life limiting disease that strikes predominantly in children and adolescents. The TrialNet clinical research network, the focus of the proposal, is charged with designing and conducting studies aimed at preventing or delaying the onset or progression of type 1 diabetes, both highly relevant public health goals

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DK061042-12S1
Application #
8831771
Study Section
Special Emphasis Panel (ZDK1-GRB-R (O1))
Program Officer
Leschek, Ellen W
Project Start
2001-09-29
Project End
2014-06-30
Budget Start
2013-05-01
Budget End
2014-06-30
Support Year
12
Fiscal Year
2014
Total Cost
$15,164
Indirect Cost
$5,324
Name
Stanford University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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
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
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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