Islet cell transplant program for type 1 diabetes successful across international centers

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Orlando, FL (June 6, 2004) -- The Edmonton Protocol for transplanting islets, through an injection that frees people with diabetes from daily insulin injections, has been shown to be effective and safe in its first international multicenter trial, according to a report here today at the American Diabetes Association's 64th Annual Scientific Sessions.

"We are delighted that the success of the protocol has now been replicated internationally in our Immune Tolerance Network trial, in which nine centers in the United States, Canada and Europe have participated over the past four years," said James Shapiro, MD, PhD, Director of the Clinical Islet Transplant Program, University of Alberta, Edmonton, Canada.

He reported that 19 of 36 participants continue to be insulin-independent for up to one year of follow-up after their transplant -- five of them having achieved such independence after only one infusion, seven after two infusions, and seven more after three infusions. Of the 17 participants who continue to require insulin, seven have derived some benefit with ongoing partial islet graft function and improvement in their ability to manage their diabetes.

The Edmonton Protocol breakthrough occurred because of: exquisite care in the isolation and preparation of islets; use of a unique drug combination and timing of their use to protect the islets and prevent their rejection; and selection of only patients most likely to benefit from the transplant and participate successfully in the trial.

Understanding diabetes

More than 18 million Americans have diabetes, a group of serious diseases characterized by high blood glucose (sugar) levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease and amputations. It is the fifth leading cause of death by disease in the U.S.

Estimates are that as many as one million or more Americans have type 1 diabetes, an immune-mediated disease that leads to destruction of the insulin-producing beta cells in the pancreas and the need for daily insulin injections throughout life. Type 1 usually arises in children or young adults.

While most people with type 1 can manage their diabetes well with insulin shots, others have an unstable form of the disease. Despite their best attempts to keep their blood glucose in check, they have wide swings in their blood glucose levels and dangerous -- even potentially fatal -- highs and lows. Such people -- called metabolically labile -- may be potential candidates for islet transplantation. Some other inclusion criteria for the trial included recurrent low blood glucose, the development of diabetes complications, weight and adequate kidney function.

How islet transplantation works

Islets are the insulin-producing cells in the pancreas. They are removed from cadavers and purified. Camillo Ricordi, MD, of the University of Miami, developed the original method for high quality, high yield islet preparation, which continues to be refined and improved upon by him and others involved in the protocol. The cells from one or more cadavers may be needed for each transplant. Because only cells -- rather than a partial or whole pancreas -- are being transplanted, a major surgical operation is not required for the transplant. Instead, the cells are delivered by an intravenous infusion into a vein -- the portal vein that goes into the liver.

"The cells then nest in the liver where they gain a new blood supply and are able to respond to moment to moment variation in blood sugar by making appropriate amounts of insulin," explained Dr. Shapiro. "The transplanted cells begin responding immediately and continue improving over the first few weeks."

Unique drug combination

The immunosuppressive drug combination used by the Edmonton Protocol is unique in many respects. The introduction of sirolimus enables the group to avoid using steroids, which are toxic to islets and can cause insulin resistance; this was the first protocol in 10 years that did not use steroids to prevent immune rejection. Further, use of sirolimus enabled them to use another drug in the combo, tacrolimus, at much lower doses -- also yielding a gentler impact on the islets. The third drug, daclizumab, is another immune suppressant that is used only for a brief period after the transplant to stop initial rejection.

Highest success rate in most experienced centers

Of the nine sites in the Immune Tolerance Network multicenter trial, those centers with the most previous experience with the protocol had the highest success rate in the trial: three sites had 75 to 100 percent success, five sites achieved 25 to 66 percent success, and one site had 0 percent success in terms of achieving insulin independence.

All patients will continue to be followed for three years after final transplant.

"We are gratified that centers around the world are developing renewed enthusiasm for clinical islet transplantation due to the Edmonton Protocol and more recent variants of the technique," said Dr. Shapiro, noting that more than 350 patients worldwide have been transplanted using similar approaches. "In the years ahead, as we enroll further patients, we look forward to exciting new approaches that will prevent rejection without the need for immunosuppressive drugs and to increasing engraftment efficiency so that we can routinely have success with one infusion."

Transplantation is not a cure

"Islet transplantation is not a cure for diabetes but rather an alternative treatment suitable only for highly selected patients with unstable forms of type 1 diabetes that cannot be effectively controlled with insulin injections," said Dr. Shapiro. He emphasized that those who receive islet transplants currently must take potent immunosuppressive drugs to prevent rejection of the transplanted islets for the rest of their lives -- and that such drugs may cause mouth ulcers (which usually go away) and increase their risks of infection and, perhaps, some types of cancer.

Dr. Bernhard Hering of the University of Minnesota and Dr. Jonathan Lakey of the University of Alberta, as well as Dr. Camillo Ricordi of the University of Miami, worked closely with Dr. Shapiro in taking the trial forward as a multicenter effort.

The American Diabetes Association is the nation's leading voluntary health organization supporting diabetes research, information, and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities. For more information, please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit www.diabetes.org. Information from both these sources is available in English and Spanish.