This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The objective of this application is to utilize GCRC resources to transplant human pancreatic islets (insulin-producing cells) for the treatment of type 1 diabetes in patients who have kidney failure and have previously received a kidney transplant as a result of diabetic kidney disease. Islet transplants have been performed in nearly 400 patients with type1 diabetes from the early 1970's to 2000, but prior to the 'Edmonton experience', only forty-one recipients of this cohort had achieved insulin independence following transplantation. Islet transplantation as a treatment for type1 diabetes has dramatically improved with successes reported at the University of Alberta in Edmonton followed by multiple other centers around the world since the year 2000. This group demonstrated consistent reversal of Type1 diabetes following sequential islet transplantation from two donor pancreases and subsequent immunosuppression with the interlukin-2 receptor antibody daclizumab, sirolimus, and low-dose tacrolimus. The success of the Edmonton Protocol has provoked the creation of an NIH-funded clinical trial (the Immune Tolerance Network Islet Transplant Trial enlisting 10 centers worldwide to emulate the methodology of the U of Alberta) and the development of 'Islet Cell Resource Centers' (ICRs) funded by the NIH (NCRR) to optimize the use of each pancreas for potential transplant. Our center, the University of Colorado Health Sciences Center, was one of 10 centers selected for participation as an Islet Cell Resource Center. At present, our laboratory has gained NIH approval for islet cell isolation under cGMP guidelines and has performed 64 pancreatic islet isolation procedures over 36 months. We have initiated a clinical trial to emulate the Edmonton protocol as a standard from which to assess function and outcomes of islet transplantation (GCRC #1391) and now plan to expand the study subject population to include subjects who are already on immunosuppressive medications to sustain a previous kidney transplant. The objective of this study is to assess the safety and efficacy of islet allotransplantation for the re-establishment of stable blood sugar control in patients with type 1 diabetes and stable kidney transplant function in a single-center pilot study. Potential candidates for islet allotransplantation will include patients greater than or equal to 18 years of age with type 1 diabetes, who have had stable kidney transplant function, and who are on medications identical to the above-mentioned islet transplant trials. Adverse events will be monitored and recorded throughout the first two years post-transplant. The proportion of type 1 diabetic islet allograft recipients with full (insulin independence and HbA1c7%) and partial (insulin dependence, basal or stimulated C-peptide levels of greater or equal to 0.5ng/mL and glycated hemoglobin less than or equal to 7%) islet graft function at 3 months post transplant and beyond will be assessed.
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