International trial of the Edmonton protocol for islet transplantation.
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].).
Shapiro
A M James
AM
Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada. shapiro@islet.ca
Ricordi
Camillo
C
Hering
Bernhard J
BJ
Auchincloss
Hugh
H
Lindblad
Robert
R
Robertson
R Paul
RP
Secchi
Antonio
A
Brendel
Mathias D
MD
Berney
Thierry
T
Brennan
Daniel C
DC
Cagliero
Enrico
E
Alejandro
Rodolfo
R
Ryan
Edmond A
EA
DiMercurio
Barbara
B
Morel
Philippe
P
Polonsky
Kenneth S
KS
Reems
Jo-Anna
JA
Bretzel
Reinhard G
RG
Bertuzzi
Federico
F
Froud
Tatiana
T
Kandaswamy
Raja
R
Sutherland
David E R
DE
Eisenbarth
George
G
Segal
Miriam
M
Preiksaitis
Jutta
J
Korbutt
Gregory S
GS
Barton
Franca B
FB
Viviano
Lisa
L
Seyfert-Margolis
Vicki
V
Bluestone
Jeffrey
J
Lakey
Jonathan R T
JR
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
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D007518:Isoantibodies