title: International trial of the Edmonton protocol for islet transplantation.
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].).
authors.affiliation: Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada. shapiro@islet.ca
authors.forename: A M James
authors.initials: AM
authors.lastname: Shapiro
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Hering
authors.forename: Hugh
authors.initials: H
authors.lastname: Auchincloss
authors.forename: Robert
authors.initials: R
authors.lastname: Lindblad
authors.forename: R Paul
authors.initials: RP
authors.lastname: Robertson
authors.forename: Antonio
authors.initials: A
authors.lastname: Secchi
authors.forename: Mathias D
authors.initials: MD
authors.lastname: Brendel
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Brennan
authors.forename: Enrico
authors.initials: E
authors.lastname: Cagliero
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Alejandro
authors.forename: Edmond A
authors.initials: EA
authors.lastname: Ryan
authors.forename: Barbara
authors.initials: B
authors.lastname: DiMercurio
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Polonsky
authors.forename: Jo-Anna
authors.initials: JA
authors.lastname: Reems
authors.forename: Reinhard G
authors.initials: RG
authors.lastname: Bretzel
authors.forename: Federico
authors.initials: F
authors.lastname: Bertuzzi
authors.forename: Tatiana
authors.initials: T
authors.lastname: Froud
authors.forename: Raja
authors.initials: R
authors.lastname: Kandaswamy
authors.forename: David E R
authors.initials: DE
authors.lastname: Sutherland
authors.forename: George
authors.initials: G
authors.lastname: Eisenbarth
authors.forename: Miriam
authors.initials: M
authors.lastname: Segal
authors.forename: Jutta
authors.initials: J
authors.lastname: Preiksaitis
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Korbutt
authors.forename: Franca B
authors.initials: FB
authors.lastname: Barton
authors.forename: Lisa
authors.initials: L
authors.lastname: Viviano
authors.forename: Vicki
authors.initials: V
authors.lastname: Seyfert-Margolis
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bluestone
authors.forename: Jonathan R T
authors.initials: JR
authors.lastname: Lakey
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000628:therapy*; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000379:methods* / Q000592:standards; D007518:Isoantibodies / Q000097:blood; D008875:Middle Aged; D009894:Opportunistic Infections / Q000453:epidemiology; D011169:Portal Vein; D015203:Reproducibility of Results; D019172:Transplantation Conditioning / Q000592:standards
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D007518:Isoantibodies