ACTIVE PROGRAMS

The European Consortium of Islet Transplantation  is carrying out 3 different specific programs:

1) “ECIT ISLETS FOR BASIC RESEARCH PROGRAM”. 
Research activity related to beta cell biology in Europe has drastically increased over the recent years, leading to a significant rise in the demand for human material. All of the clinical islet isolation and transplantation core centers have a long-standing tradition to provide human islets of high quality and purity for specific research to national and international collaborators. From these experiences and from similar islet distribution programs it has become evident, that sufficient supply and further stimulation of translational research is critically dependent from enhanced availability of high-quality human islet preparations.
For this reason ECIT decided to start a program for islet distribution in Europe. The program actually involves Milan, Geneve, Uppsala and Lille centers and it is supported by JDRF (Grant Name: Islets For Research; Grant Number: 31-2008-416).

2) “ECIT CLINICAL TRIAL: A MULTI-STEP TRIAL TOWARDS SINGLE DONOR ISLET TRANSPLANTATION IN TYPE 1 DIABETIC PATIENTS, USING CALCINEURIN INHIBITOR-FREE IMMUNOSUPPRESSION”
The goal of this clinical trial is to prove safety, feasibility and efficacy of a protocol including a pre-treatment with rapamycin and CNI-free immunosuppression in type 1 diabetic  patients undergoing islet transplantation.  We designed the clinical trial to be a single-group, phase 1–2 trial. The two international centers —Milan and Geneve — that participated in the study use a common protocol of islet preparation and post-transplantation care.
The immunosuppressive protocol consists of a maintenance therapy with rapamycin (0.1 mg/kg/day, targeting serum levels of 12-15 ng/ml for the first 1-3 months post each infusion and serum levels of 10-12 ng/ml thereafter) + MMF (2 g/day) which follows a rapamycin treatment (0.1 mg/kg/day [targeting serum levels of 8-10 ng/ml], starting 30 days prior to islet transplantation), an induction therapy with ATG (1.5 mg/kg/day for 4 days starting at day -1) and a steroid bolus (methyl-prednisolone, 500 mg bolus, day -1) + low dose steroids (prednisone, 10 mg/day) and Anakirna (100 mg/day) for 2 weeks (starting at day –1). Administration of ATG was limited to the first islet infusion.
Our target enrollment is 10 subjects, with 5 subjects per site, on the basis of available funding. Each patient should receive at least 10,000 IE/kg. Up to three islet infusions are permitted per subject until insulin independence is reached, on condition that partial islet function persisted after the preceding transplantation. The study has a planned follow-up of 3 years for all subjects after their last transplantation.
The primary end point is defined as the proportion of subjects with an HbA1c <6.5% and free of severe hypoglycemic  events at 1 year after the first islet cell infusion. 
Secondary end points include insulin independence with adequate glycemic control throughout follow-up; improved values for levels of glycated hemoglobin, the mean amplitude of glycemic excursions, basal and stimulated blood C-peptide levels in response to arginine challenge and a reduction in the need for insulin, as compared with baseline.  Outcomes are compared to those of the historical islet transplant recipients. Enrollment  is still ongoing
“ECIT Clinical trial” involves Milan and Geneve  and it is supported by JDRF (Grant Name: A Multi-step trial towards single donor islet transplantation in type 1 diabetic patients, using calcineurin inhibitor-free immunosuppression; Grant Number: 6-2006-1098)

3) SCIENTIFIC ACTIVITY RELATED TO THE ECIT CLINICAL TRIAL. 
The objective of this program  is to improve the success rate of islet transplantation by defining pre- and post-transplant parameters that are linked to outcome. Starting from a cohort of islet transplanted patients provided by the European Consortium for Islet Transplantation Clinical Trial  (Grant Number: 6-2006-1098) we planned to:

a) investigate the relationship between pre-transplant hormone content (insulin, proinsulin and c-peptide) and cell composition (% beta cells, alpha cells, acinar cells, non-granulated duct cells and damaged cells) of isolated islets and post-transplant metabolic or immunologic  events (i.e. graft function, graft rejection).
b) investigate the relationship between pre-transplant islet insulin synthesis/release and post-transplant graft function.
3) investigate the relationship between pre-transplant islet energetic status (ADP/ATP) and post-transplant graft function.
d) investigate the relationship between post-transplant blood insulin, glucagon and granzyme B mRNAs  and metabolic or immunologic  events (graft failure, graft rejection).
e) investigate the relationship between pre-transplant cytokine/chemokine release from isolated islets and post-transplant metabolic or immunologic  events (i.e. graft failure, graft rejection).
 
This program involves Milan, Geneve, Uppsala and Brussel centers and it is supported by JDRF  (JDRF award # 9-2004-384)