A clinical research consortium sponsored by NIAID and JDRF
Ricordi C, DiMercurio B, Lindblad R, Cagliero E, Robertson RP, Berney T, Ramos E, Viviano L, Shapiro J, Hering B, Brendel M, Oberholzer J, Secchi A, Brennan D, Ryan E, Lakey J
University of Alberta, Edmonton, Canada University of Miami, Miami, FL University of Minnesota, Minneapolis, MN National Institutes of Health, Bethesda, MD EMMES Corporation, Rockville, MD Massachusetts General Hospital, Boston, MA Justus-Liebig University, Giessen, Germany Pacific Northwest Research Institute, Seattle, WA University of Geneva, Geneva, Switzerland University of Milan, Milan, Italy Washington University, St Louis, MO Immune Tolerance Network, San Francisco, CA
The Immune Tolerance Network international multicenter trial using the Edmonton Protocol was designed to explore the safety and efficacy of islet-alone transplantation in patients with Type 1 diabetes. Stringent enrollment criteria included metabolic lability, recurrent hypoglycemia or progressive complications of diabetes. Only optimal patients were selected based on strict weight limitation (<= 70kg) and adequate renal reserve (CC >80ml/min/1.73m2. The trial involved 9 sites in Canada, the US and Europe, with a target enrollment of 36 patients. A total of 49 islet transplants have been performed in 32 patients to date (1 transplant (n=16); 2 transplants (n=15); 3 transplants (n=1)). Of 17 completed transplants, 14 (82.3%) are insulin independent currently. 4/32 (12.5%) achieved insulin independence with islets prepared from a single donor. The mean islet implant mass was 377,256 +/- 82,256 IE. All 32 patients were C-peptide negative prior to transplant. Currently 30/32 (94%) are C-peptide positive post transplant. Two life-threatening events have been reported, both were neutropenia <500 requiring hospitalization and gCSF. Bleeding following percutaneous portal access was reported in 4/49 (8%) procedures (1/4 was transfused). The more common complications included mouth ulceration, transient elevation in liver function, neutropenia, leukopenia, thrombocytopenia, and hypercholesterolemia. There have been no deaths reported to date. There have been no reports of malignancy or PTLD. There has been no CMV disease or seroconversion to date. There has been no reported thrombosis of the portal vein.
Conclusion: The preliminary findings from this trial support the safety and efficacy of islet-alone transplantation, and indicate that the Edmonton Protocol may be successfully replicated across centers internationally. Standardization of islet processing between centers remains a major challenge, but it should not delay the development of successful clinical protocols in the field of islet transplantation.
