Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation

Phase 2 Study of Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation With Steroid Free Immunosuppression

This single center phase 2 clinical trial, is designed for confirming the efficacy and safety of sequential islet allotransplantation with steroid free immunosuppression in patients with previous kidney transplantation.

The beneficial effects of glycemic control on both survival and function of transplanted kidneys in patients with type 1 diabetes mellitus have been recognized.

The purpose of this study is to reverse hyperglycemia and insulin dependency, by islet cell transplantation, in patients with type 1 diabetes mellitus who have a stable kidney allograft.

The study primary efficacy endpoint is graft survival defined as insulin independence and HbA1c < 8% at 1 year post first transplant. Secondary outcomes are graft function and metabolic control

The immunosuppression protocol for the kidney graft was converted to sirolimus+tacrolimus regimen 6 months before islet transplantation to exclude negative effects on kidney graft function.

Inclusion Criteria:

• Type 1 diabetes mellitus. Documentation of negative basal and stimulated C-peptide and diagnosis of diabetes for at least 5 years.
• Recipient of renal transplant with good function (creatinine clearance >/=60 ml/min)
• Stable immunosuppression consisting of any combination of sirolimus, tacrolimus for at least 6 months, without major complications
• Ability to give informed consent.
• Age greater than or equal to 18 years or less than or equal to 65 years
• No evidence of liver disease (liver enzymes < twice the upper limit of normal)

Exclusion Criteria:

• Age below 18 years and above 65 years
• Significant cardiovascular disease, including non-correctable coronary artery disease and/or recent myocardial infarction(within last 12 months); extensive peripheral vascular disease not correctable by surgery, unstable angina
• Untreated proliferative retinopathy.
• Recent Cerebrovascular accident (within last 12 months)
• Recent unresolved acute infection, or chronic infection, including tuberculosis, HIV, HBV, HCV, CMV or positive skin test for TB
• Any history of malignancy, except squamous or basal skin cancer or in situ cancer of the cervix.
• History of non-compliance, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin pump therapy.
• Psychiatric illness that is untreated, or likely to interfere significantly with transplantation despite treatment.
• Pregnant women, women intending future pregnancy, women of reproductive potential who are unable or unwilling to follow effective contraceptive measures for the duration of immunosuppressive therapy
• Fasting C-peptide > 0.2 ng/ml
• Creatinine > 25mg/l
• Alkaline phosphatase, total bilirubin, Alanine Aminotransferase (ALT)or Aspartate Aminotransferase (AST) > twice the upper limit of normal
• Significant liver disease (elevation of liver enzymes > twice the upper limit of normal for each of ALT and AST, liver masses including portal vein thrombosis, evidence of portal hypertension, or significant, untreated gallbladder disease (i.e., gallstones).