allogeneic islet transplantation for the treatment of type 1 diabetes

Conditions: Patients With Type 1 Diabetes

Summary: it is a multicentre, sequential, phase ii clinical trial, aiming at evaluating the allogeneic islet transplantation for the treatment of type 1 diabetes. 19 patients with type 1 diabetes will be included and ideally distributed evenly: patients with unstable diabetes without renal insufficiency (ai group for "islet alone" by the international customary determination) and patients with a functioning kidney transplant (iak group for "islet after kidney"). the main endpoint will be defined by the restoration of normal glycemic control without insulin at 6 months after graft.


Eligibility criteria:
inclusion criteria: * patients with type 1 diabetes * 18 \<age \<55 years * plasma c-peptide \<0.2 ng/ml basal and stimulated glucagon * evolution of diabetes for more than 5 years * regular patient follow-up (\> or equal to 2 visits per year from the same diabetologist) * patient who received the information and have given their consent in writing * absence of hiv, hepatitis b and hepatitis c, htlv-1-2 * abo compatibility with the donor * cross match negative * anti-hla antibodies (class i and / or class ii) detected by lymphocytotoxicity \<20% * pcr negative for the bk virus in the blood (so as not to amplify the bk virus replication with the atg). * accepting patients effective contraception during the study period for patients in group ia * glomerular filtration rate estimated by the mdrd\> 50 ml/min/1.73m2 * no perception of hypoglycaemia (less than 0.54 mg/dl glucose) at least one value documented in the two years preceding and/or * occurrence of at least one severe hypoglycemic episode (with a third required) and unexplained in the two years before and/or at least two episodes of ketoacidosis per year * average hba1c\> 8.5% over two years, despite intensified treatment (basal pattern, bolus) • for patients in the iak * functional renal graft for at least 1 year * glomerular filtration rate\> 50 ml/min/1.73 m2 * proteinuria \<0.5 g/day * absence of acute rejection in renal previous 6 months exclusion criteria: * bmi \> 28 * need insulin \> 1 u/kg per day * pregnancy, lactation * intention of childbearing for the two sexes * psychiatric disorders * inability to communicate or cooperate with the investigator * lack of therapeutic compliance, including hba1c \> 12% * chronic liver disease * progressive heart disease myocardial infarction within 6 months prior to inclusion, unbalanced chd) * proliferative retinopathy unstabilized * history of cancer, whatever the date, except for basal or squamous cell skin cancers over 1 year. * systemic infection * chronic high risk of requiring corticosteroids * need for long-term corticosteroid, outside that specified in renal transplantation, the patients will be weaned before transplantation * anticoagulant vitamin k or antiplatelet treatments * disorders of hemostasis tp \ 1.5 times the control * anti-hla antibodies ( class i and/or class ii ) detected by lymphocytotoxicity \> 20% * platelets \< 100 giga/l and/or neutrophils \<1.5 giga/l * chronic intoxication by alcohol, tobacco, or other substance (abstinence \> 6 months required) * active infection by hepatitis b, hepatitis c and hiv, htlv-1-htlv2 * ascites

Keywords: diabetes transplantation