EFFECTS OF RITUXIMAB ON THE PROGRESSION OF 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. Study Design: TrialNet is an NIH funded multicenter group created to study immunotherapies in prevention, delay and treatment of Type 1 diabetes. The proposed study is a two-arm, multicenter, randomized, double-masked, placebo-controlled clinical trial. Both groups will receive standard intensive diabetes treatment with insulin and dietary management. Treatment Description: Rituximab (RITUXANR, Genentech and Biogen Idec) is a chimeric murine/human monoclonal antibody approved for the treatment of B-cell non-Hodgkin's lymphoma. The antibody binds to the CD20 antigen on the surface of B cells and mediates B-cell depletion. Participants randomly assigned to rituximab treatment will receive four doses of 375 mg/m2 IV each week apart. Study Duration: Total duration is approximately 4 years (2 years accrual and 2 years follow-up). Follow-up for up to 4 years will continue for those who have persistence of beta cell function at 2 years and/or detectable immunologic effects of treatment by descriptive analysis until the disappearance of detectable beta cell function or resolution of immunologic changes. Objective: To assess the safety, efficacy, and mode of action of rituximab, anti-CD20 monoclonal antibody, for the treatment of individuals with new onset type 1 diabetes. Primary Outcome: The primary statistical hypothesis to be assessed in this study is whether the mean C-peptide value for study subjects on rituximab differs significantly from the mean value for placebo subjects assessed at one year of follow-up. Secondary Goals: The study will examine the effect of the proposed treatment on surrogate markers for immunologic effects, namely disease-specific outcomes and immunological outcomes. Major Inclusion Criteria: Type 1 diabetes within past 3 months; age 8-45 years; and at least one diabetes associated autoantibody.