Doctor James Shapiro

Edmonton Protocol - Trials

Originally, all islet cell transplant programs were based on the Edmonton Protocol. Since then, much of the research is being done with the Edmonton Protocol as a basis. For a list of current US trials, go to www.clinicaltrials.gov

 

The New England Journal of Medicine: Article

 

The New England Journal of Medicine - September 28, 2006 Number 13

International Trial of the Edmonton Protocol for Islet Transplantation

A.M. James Shapiro, M.D., Ph.D., Camillo Ricordi, M.D., Bernhard J. Hering, M.D., Hugh Auchincloss, M.D., Robert Lindblad, M.D., R. Paul Robertson, M.D., Antonio Secchi, M.D., Mathias D. Brendel, M.D., Thierry Berney, M.D., Daniel C. Brennan, M.D., Enrico Cagliero, M.D., Rodolfo Alejandro, M.D., Edmond A. Ryan, M.D., Barbara DiMercurio, R.N., Philippe Morel, M.D., Kenneth S. Polonsky, M.D., Jo-Anna Reems, Ph.D., Reinhard G. Bretzel, M.D., Federico Bertuzzi, M.D., Tatiana Froud, M.D., Raja Kandaswamy, M.D., David E.R. Sutherland, M.D., Ph.D., George Eisenbarth, M.D., Ph.D., Miriam Segal, Ph.D., Jutta Preiksaitis, M.D., Gregory S. Korbutt, Ph.D., Franca B. Barton, M.S., Lisa Viviano, R.N., Vicki Seyfert-Margolis, Ph.D., Jeffrey Bluestone, Ph.D., and Jonathan R.T. Lakey, Ph.D.

Editorial

by Bromberg, J. S.

Abstract

Background Islet transplantation offers the potential to improve glycemic control in a subgroup of patients with type 1 diabetes mellitus who are disabled by refractory hypoglycemia. We conducted an international, multicenter trial to explore the feasibility and reproducibility of islet transplantation with the use of a single common protocol (the Edmonton protocol).

Methods

We enrolled 36 subjects with type 1 diabetes mellitus, who underwent islet transplantation at nine international sites. Islets were prepared from pancreases of deceased donors and were transplanted within 2 hours after purification, without culture. The primary end point was defined as insulin independence with adequate glycemic control 1 year after the final transplantation.

Results

Of the 36 subjects, 16 (44%) met the primary end point, 10 (28%) had partial function, and 10 (28%) had complete graft loss 1 year after the final transplantation. A total of 21 subjects (58%) attained insulin independence with good glycemic control at any point throughout the trial. Of these subjects, 16 (76%) required insulin again at 2 years; 5 of the 16 subjects who reached the primary end point (31%) remained insulin-independent at 2 years.

Conclusions

Islet transplantation with the use of the Edmonton protocol can successfully restore long-term endogenous insulin production and glycemic stability in subjects with type 1 diabetes mellitus and unstable control, but insulin independence is usually not sustainable. Persistent islet function even without insulin independence provides both protection from severe hypoglycemia and improved levels of glycated hemoglobin. (ClinicalTrials.gov number, NCT00014911 [ClinicalTrials.gov] .)

Despite substantial improvements in insulin therapy and the care of patients with type 1 diabetes mellitus, a subgroup of patients is disabled by refractory hypoglycemia. Cell-based therapy with islet transplantation offers the possibility of improved glycemic control. The past three decades have witnessed substantial progress in islet transplantation. Before the year 2000, few centers performing islet transplantation achieved high rates of sustainable insulin independence after this procedure among patients with type 1 diabetes mellitus. In 2000, Shapiro et al. reported their initial findings with up to a year of follow-up in seven consecutive subjects treated with glucocorticoid-free immunosuppressive therapy combined with infusion of an adequate mass of freshly prepared islets from two or more pancreases from deceased donors. In all seven subjects, insulin independence was achieved, with tight glycemic control and correction of glycated hemoglobin levels. This treatment became known as the Edmonton Protocol. The goal of our study was to explore the feasibility and reproducibility of this protocol for islet preparation and management after transplantation, including immunosuppression.