Edmonton Protocol

The development of the Edmonton Protocol as it stands today stems from the large body of research on pancreatic islet isolation and transplantation, which was led by Dr Ray Rajotte and began in 1972 at the University of Alberta's Surgical Medical Research Institute (SMRI). During those early years in islet research at the University of Alberta, Rajotte developed a technique for the purification and cryopreservation of islets. Over the next 10 years, research led by Rajotte gave rise to the idea that insulin-dependence in type 1 diabetes could be overcome by transplanting purified islets without the need to transplant the whole pancreas. To this end, Rajotte founded the University of Alberta`s Islet Transplantation Group in 1982.

At that time, the group consisted of Rajotte as Director, Garth Warnock, Norman Kneteman, and Edmond Ryan. The Islet Transplantation Group devoted the next 7 years of research to isolation of viable islets from cadaveric pancreases and in 1989, they carried out Canada's first islet transplant. Using a combination of freshly isolated and cryopreserved islets, long term insulin-independence was achieved in their 3rd transplant patient who remained free of insulin injections for 2.5 years post-transplant. These results were encouraging but many hurdles still had to be overcome with the procedure.

At that time, islet purification from whole pancreas still needed to be improved. In addition, islet transplants were being done in conjunction with kidney transplants in type 1 diabetes patients. During this procedure, immunosuppressive protocols were tailored to the kidney transplant and the drugs used were toxic to islet function and engraftment. As a result, newly transplanted islets were often short lived in the patient.

Over the next 10 years, research on clinical islet transplantation continued at the University of Alberta and around the world. Rajotte continued to build Transplantation Group by recruiting Greg Korbutt (1996), Jonathan Lakey (1997) and James Shapiro (1998) to the team. Shapiro was named the Clinical Director of the Islet Transplantation Group and work continued on improving the islet transplant procedure.

By 1999, nearly 270 patients had received islet transplants worldwide, but only 12% of patients were still insulin-independent one week following transplant, and only 10% of patients retained insulin-independence one year after transplant. These results were not encouraging but the Islet Transplant Group did not give up. Having spent 10 years between 1989 and 1999 doing research on improved islet purification methods and immunosuppressive protocols, the Islet transplantation Group at the University of Alberta was ready to undertake a new clinical trial where they performed solitary islet transplants (no kidney co-transplant) on seven type 1 diabetes patients using a novel glucocorticoid-free immunosuppressive regimen.

Using this new transplant protocol, all seven recipients became insulin-independent after receiving islets from several donors (11,500 islets/kg body weight). The results were published in the New England Journal of Medicine in July of 2000.

With this clinical trial, the islet transplantation success rate measured by insulin-independence at one year post transplant had been increased from 10% to 100% of patients. This giant leap forward in islet transplantation became known worldwide as the Edmonton Protocol. The success of the Edmonton Protocol has set the standard in islet transplantation and has been adopted around the world as a method to treat type 1 diabetes.

The Clinical Islet Transplant Program at the University of Alberta, is now led by James Shapiro (Director) and includes Peter Senior (Medical Director), Angela Koh (Endocrinologist), David Bigam and Kneteman (Transplant Surgeons) as well as the human islet isolation and clinical support teams.

The Clinical Islet Transplant Program continues to improve the Edmonton Protocol and is now performing more human islet transplants annually than any other center in the world. The large body of research done at the University of Alberta by Rajotte and the Islet Transplantation Group, and the current work of the Clinical Islet Transplant Program, have paved the way to this great success story.

If you are interested in further information on the Edmonton protocol, please visit the Clinical Islet Transplant Program at the University of Alberta.

Islet Transplantation in Seven Patients with Type 1 Diabetes Mellitus using a Glucocorticoid-Free Immunosuppressive Regimen

The New England Journal of Medicine, July 27, 2000