TYPE 1 DIABETES: CELLCEPT ALONE OR IN COMBINATION WITH DACLIZUMAB

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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 3-arm randomized, partially-blind, placebo-controlled comparison of Mycophenolate Mofetil (MMF) alone, MMF with Daclizumab, and oral placebo only. The effects of the treatment on the loss of b-cell function, diabetes-specific immune responses and general immune responses will be studied. We will determine whether these treatments have clinical efficacy and attempt to determine the potential mechanism of action by defining how the drug alters both diabetes-specific and general immune responses. The mechanistic studies of diabetes-specific immune responses in this trial will include studies of titers of autoantibodies, functional studies of diabetes specific T-cells and assessment of recall antigen reactivity. This trial will develop information which can be used in larger studies should the agent(s) prove to be effective. Specific Aim 1 is a clinical trial to test the hypothesis: MMF alone will preserve C-peptide levels in type 1 diabetics for 2 or more years when started at diagnosis. The study will enroll 60 subjects who will be randomized into groups of 30 to receive 750 mg/m2 or 2000 mg/day of MMF by mouth twice daily or a placebo for the MMF over the 2-yr follow-up period. The b-cell function endpoints are basal and stimulated C-peptide following Sustacal¿ and, secondarily, insulin dose, HbA1c and number of hypoglycemic events. Specific Aim 2 will examine and develop surrogate markers for immunologic effects of the proposed treatments. These are: disease-specific endpoints: autoantibody determinations, T-cell reactivity and frequency. There are immunological endpoints: T-cell reactivity to recall antigens and frequency of activated T-cells.