This proposal is submitted by The Biostatistics Center of The George Washington University to serve as the Operations Coordinating Center for TrialNet in response to RFA DK-01-004 """"""""Type 1 Diabetes TrialNet: Core Support Facilities."""""""" The functions of the Operations CoordinatingCenter (OCC) for TrialNet are to provide for thecontinuation of the ongoing DPT-1 parenteral and oral insulin primary prevention trials and to support future studies with the ultimate objective of prevention of type 1diabetes and its amelioration. As of 1997 it is estimated that worldwide about 124 million individuals had diabetes mellitus, of which 3.5 million have type 1 diabetes, the majority of these having an onset during childhood. In the US alone,approximately 15.7 million individuals, or 5.9% of the total population have diabetes, with at least 500,000 or 0.12% of the US population, 1.2 per 1000 population, then having type 1 diabetesmellitus. The onset of type 1 diabetes mellitus is one step in a chain of events that begins at the moment of conception. Genetic polymorphisms,principallyHLA haplotypes, have been identified that confer an increased risk of developing diabetes, or are protective.Genetic defects render an individual susceptible to an aberrant immunologicresponse to one of possibly many environmental insults. Following the environmental trigger, the T-cells begin an assault on the insulin- producing beta or islet cells of the pancreas. This autoimmuneresponse is manifest by the appearance of antibodies and the subsequent loss of first phase insulin response. Thereafter beta cell function declines. This makes it feasible to conduct studies of the genetics of type 1 diabetes and immune tolerance, the role of environmental pathogens, the characterization of autoimmunity and immune tolerance, evaluation of the risk of developing diabetes, and various interventions aimed at immune tolerance or preservation of beta cell function. The objective of The George Washington University Biostatistics Center is to apply our considerable resources and experience to the completion of the following main tasks to ensure the clinical and scientific success of the multifaceted studies to be undertaken and completed by TrialNet. (1) Study Coordination and Planning: We will help establish an efficient organizational structure to ensure that all activities advance in a coordinated fashion. (2) Data Management Activities: We will apply our established systems for on-going data collection and data management, and will generate periodic reports summarizing the execution of the trial. (3) Statistical Analysis: We will provide statistical leadership in the design of studies, and perform interim and final analyses in an expeditious and timely manner. (4) Documentation: We will provide for the orderly closeout of all studies with complete documentation and dissemination of relevant materials to the NIH and the public.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK061055-07
Application #
7280757
Study Section
Special Emphasis Panel (ZDK1-GRB-C (O2))
Program Officer
Leschek, Ellen W
Project Start
2001-09-29
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
7
Fiscal Year
2007
Total Cost
$11,185,161
Indirect Cost
Name
George Washington University
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
043990498
City
Washington
State
DC
Country
United States
Zip Code
20052
Writing Committee for the Type 1 Diabetes TrialNet Oral Insulin Study Group; Krischer, Jeffrey P; Schatz, Desmond A et al. (2017) Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes: A Randomized Clinical Trial. JAMA 318:1891-1902
Marwaha, A K; Panagiotopoulos, C; Biggs, C M et al. (2017) Pre-diagnostic genotyping identifies T1D subjects with impaired Treg IL-2 signaling and an elevated proportion of FOXP3+IL-17+ cells. Genes Immun 18:15-21
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
Sosenko, Jay M; Skyler, Jay S; Palmer, Jerry P et al. (2015) The development, validation, and utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS). Curr Diab Rep 15:49
Ismail, Heba M; White, Kama S; Krischer, Jeffrey P et al. (2015) First test effect in intravenous glucose tolerance testing. Pediatr Diabetes 16:129-37
Herold, Kevan C; Usmani-Brown, Sahar; Ghazi, Tara et al. (2015) ? cell death and dysfunction during type 1 diabetes development in at-risk individuals. J Clin Invest 125:1163-73
Bingley, Polly J; Rafkin, Lisa E; Matheson, Della et al. (2015) Use of Dried Capillary Blood Sampling for Islet Autoantibody Screening in Relatives: A Feasibility Study. Diabetes Technol Ther 17:867-71
Bollyky, Jennifer B; Xu, Ping; Butte, Atul J et al. (2015) Heterogeneity in recent-onset type 1 diabetes - a clinical trial perspective. Diabetes Metab Res Rev 31:588-94
Loechelt, Brett J; Green, Michael; Gottlieb, Peter A et al. (2015) Screening and Monitoring for Infectious Complications When Immunosuppressive Agents Are Studied in the Treatment of Autoimmune Disorders. J Pediatric Infect Dis Soc 4:198-204
Miao, Dongmei; Steck, Andrea K; Zhang, Li et al. (2015) Electrochemiluminescence assays for insulin and glutamic acid decarboxylase autoantibodies improve prediction of type 1 diabetes risk. Diabetes Technol Ther 17:119-27

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