International Trial of the Edmonton protocol for Islet Transplantation

Background This international multicenter trial explores the feasibility and reproducibility of islet transplantation using a single common protocol (Edmonton Protocol ) for islet manufacture and post-transplant management. Methods A total of 36 subjects underwent islet transplantation at 9 international sites (6 in North America, 3 in Europe). Islets were prepared from cadaveric donors, purified, and transplanted within two hours, without culture. The primary endpoint was defined as the proportion of subjects that remained insulin independent with adequate glycemic control at one year following their final transplant. Results 16/36 (44%, CI 30% - 61%) subjects achieved the primary endpoint, 10 (28%) demonstrated partial islet function, and 10 had complete graft loss before one year. 22/36 (61%) derived benefit at one year post final transplant as demonstrated by insulin independence or reduced insulin requirement, HbA1C <6.5%, stimulated C-peptide >0.3ng/mL and protection from severe hypoglycemia. Of 21/36 (58%) subjects attaining primary endpoint criteria at any point throughout the trial, 15/21 (71%) became dependent on insulin again by two years. Conclusions This multicenter trial confirms that islet transplantation successfully restores long-term endogenous insulin production and glycemic stability in T1DM subjects with unstable baseline control, but insulin independence is usually evanescent over time. Persistent islet function despite loss of insulin independence provided complete protection from severe hypoglycemia and improved HbA1C. Islet transplantation is an appropriate therapy for highly selected subjects with severe hypoglycemia or labile diabetes, provided all other attempts to stabilize glycemic control have been exhausted.