The University of Florida intends to continue as a Clinical Center as part of the nationally constituted diabetes trial network (Type 1 Diabetes TrialNet), in order to ultimately study therapies aimed at preventing or delaying the development of type 1 diabetes (T1D). The University of Florida Clinical Center has participated in nine approved NIH TrialNet protocols including the Natural History Study, the Mycophenolate Mofetil (MMF) / Dacluzimab (DZB) Trial, the Anti-CD20 Trial, the CTLA-4 lg Trial, the Oral Insulin Study, the comparative Mixed Meal Tolerance (MMTT) - Glucagon Stimulation (GST) C-peptide Study, the T-Cell Assay Validation Study, the Nutrition Intervention to Prevent Diabetes (NIP) Study, and the T1D Genetics Consortium. The Center has consistently been one of the strongest performers both in the recruitment of subjects and the conduct of TrialNet (and other Type 1 studies) and will work to continue oversight of its successful network of Affiliate Centers and participating physicians involved in TrialNet study recruitment and follow-up and to further expand these efforts. We intend to continue to conduct studies in patients with recent-onset diabetes aimed at preserving beta cell function and/or decreasing beta cell destruction, and, if safety and efficacy is demonstrated, implement studies using these agents aimed at the prevention of the disease. Based on (i) exciting preliminary (efficacy, mechanistic and safety) data using a combination of low-dose Anti-Thymocyte Globulin (ATG) and Granulocyte Colony Stimulating Factor (GCSF) in NOD mice, (ii) encouraging data in other human autoimmune disorders and transplantation (iii) pilot studies using each agent separately in new-onset patients, we propose to conduct a study aimed at establishing the safety, efficacy and mechanism of this combination as an intervention to slow disease progression in individuals with newly-diagnosed T1D.
The incidence of Type 1 diabetes is increasing worldwide and the disease is a tremendous burden on both afflicted individuals and society. Studies will be conducted by the University of Florida Clinical Center within the TrialNet umbrella to study therapies aimed at (i) preventing or delaying the development of type 1 diabetes in susceptible individuals (ii) preserving pancreatic islet beta cell function in patients with already established diabetes (iii) understanding the immunologic mechanisms leading to the destruction of the insulin producing cells.
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|Orban, Tihamer; Bundy, Brian; Becker, Dorothy J et al. (2014) Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: follow-up 1 year after cessation of treatment. Diabetes Care 37:1069-75|
|Arif, Sefina; Leete, Pia; Nguyen, Vy et al. (2014) Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes. Diabetes 63:3835-45|
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|Pescovitz, Mark D; Greenbaum, Carla J; Bundy, Brian et al. (2014) B-lymphocyte depletion with rituximab and *-cell function: two-year results. Diabetes Care 37:453-9|
|Kroll, Jing Lu; Beam, Craig; Li, Shaobing et al. (2013) Reactivation of latent viruses in individuals receiving rituximab for new onset type 1 diabetes. J Clin Virol 57:115-9|
|Krischer, Jeffrey P; Type 1 Diabetes TrialNet Study Group (2013) The use of intermediate endpoints in the design of type 1 diabetes prevention trials. Diabetologia 56:1919-24|
|Loechelt, Brett J; Boulware, David; Green, Michael et al. (2013) Epstein-Barr and other herpesvirus infections in patients with early onset type 1 diabetes treated with daclizumab and mycophenolate mofetil. Clin Infect Dis 56:248-54|
|Sosenko, Jay M; Skyler, Jay S; Palmer, Jerry P et al. (2013) The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients. Diabetes Care 36:2615-20|
|Weinberg, Adriana; Boulware, David; Dighero, Bonnie et al. (2013) Effect of abatacept on immunogenicity of vaccines in individuals with type 1 diabetes. Vaccine 31:4791-4|
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