Expectations and strategies regarding islet transplantation: metabolic data from the GRAGIL 2 trial.
BACKGROUND
Whether islet transplantation should be aimed at restoring insulin independence or providing adequate metabolic control is still debated. The GRAGIL2 trial was designed as a phase 1-2 study where primary outcome was the rate of insulin independence, and secondary outcome was the success rate defined by a composite score based upon basal C-peptide, HbA1c, hypoglycemic events, and exogenous insulin needs.


METHODS
C-peptide negative type 1 brittle diabetic patients experiencing severe hypoglycemia were eligible to receive a maximum of two islet preparations totalizing 10,000 IE/kg or more, with a threshold of 5,000 IE/kg for the first infusion, according to the Edmonton protocol, within the Swiss-French GRAGIL multicentric network. A sequential analysis with a triangular test was performed in every five patients after 6- and 12-month follow-up. Maximal inefficiency was set at 40% and minimal efficiency at 66%.


RESULTS
From September 2003 to October 2005, 10 patients were included. Median waiting time was 6.7 months (first injection) and 9 weeks (second injection). All but one patient received 11,089+/-505 IE/kg: one received a single graft of 5398 IE/kg. At 6 months, insulin independence and composite success rates were 6 of 10 and 6 of 10, respectively. At 12 months, insulin independence was observed in 3 of 10 patients and success in 5 of 10 patients.


CONCLUSIONS
Based upon our sequential analysis settings, islet transplantation failed to achieve the primary goal, insulin independence, but tended to succeed in reaching the secondary goal, successful metabolic control. Currently it appears to be a successful biological closed-loop glucose control method for brittle diabetes.
Badet
Lionel
L
Department of Urology, University Hospital, Lyon, France.
Benhamou
Pierre Y
PY
Wojtusciszyn
Anne
A
Baertschiger
Reto
R
Milliat-Guittard
Laure
L
Kessler
Laurence
L
Penfornis
Alfred
A
Thivolet
Charles
C
Renard
Eric
E
Bosco
Dominico
D
Morel
Philippe
P
Morelon
Emmanuel
E
Bayle
François
F
Colin
Cyrille
C
Berney
Thierry
T
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007003:Hypoglycemia / Q000503:physiopathology*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009901:Optic Nerve Diseases / Q000139:chemically induced; D012720:Severity of Illness Index; D016896:Treatment Outcome
D001786:Blood Glucose; D007166:Immunosuppressive Agents; D007328:Insulin