IMMUNOTHERAPY TRIAL FOR NEW ONSET TYPE 1 DIABETES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose a multicenter, 3-arm randomized, blinded, placebo-controlled prospective study to test the hypothesis that mycophenolate (MMF) alone or MMF with daclizumab (DZB) will prolong the period of c-peptide production in subjects with new onset type 1 diabetes. Metabolic end-points will also include hemoglobin A1c and total insulin dose. A second aim of the study will examine the effect of the proposed treatment on surrogate markers for immunologic effects, namely disease-specific endpoints (autoantibody determinants, generation of alloantibodies, and T cell reactivity and frequency) and immunological endpoints. The study will be conducted jointly by the Barbara Davis Center for Childhood Diabetes and other participating TrialNet sites including the Virginia Mason Research Center in Seattle. The study is innovative in that the agents to be tested have not previously been evaluated in type 1 diabetes, but are rational choices for interventions in an autoimmune disorder. We believe the study is timely in that far less toxic immunosuppressive agents have been developed in the 10 year interval since Cyclosporine was found to preserve c-peptide production in new-onset patients. Our power projections are based on extensive previous intervention studies and the choice of agents to be tested is supported by animal studies. MMF is an effective component of anti-rejection treatment of heart, kidney and liver recipients. It is effective for the treatment of psoriasis. The DZB anti-IL2 receptor antibody selected for use with MMF is effective in treatment of acute renal rejection episodes. The safety of these agents in clinical use justifies a trial in type 1 diabetes, where 30% of new onset subjects run HbA1c levels that put them at high risk for vascular disease within 20 years.