Delayed Mycophenolate Mofetil in Single-Donor Islet Allotransplantation in Type 1 Diabetes

To assess the safety and efficacy of a new single-donor islet allotransplant protocol focusing on minimization of ischemic damage by the two-layer pancreas preservation technique, attenuation of posttransplant nonspecific inflammatory responses by etanercept and anti-thymocyte globulin, deletion/inactivation of autoreactive T cells by anti-thymocyte globulin and daclizumab induction immunotherapy, and potent yet non-diabetogenic maintenance immunosuppression with sirolimus and delayed mycophenolate mofetil instead of tacrolimus for the reestablishment of stable glycemic control in recipients with type 1 diabetes.

Inclusion criteria

• Primary islet allotransplant
• Type 1 diabetes mellitus, complicated by at least one of the following situations that persist despite intensive efforts in close cooperation with their diabetes care team:

• Metabolic lability/instability;
• Reduced awareness of hypoglycemia;
• Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months of intensive management efforts with the diabetes care team);
• Progressive secondary complications.
• Age 18 and older
• Able to give written informed consent

Exclusion criteria

• Known hypersensitivity to rabbit proteins.
• Presence of history of panel-reactive anti-HLA antibodies (>10%).
• Insufficient cardiovascular reserve.
• Creatinine clearance <60 mL/min/m2.
• Portal hypertension, abnormal liver enzyme tests, or history of significant liver disease.
• History of malignancy within 5 years.
• Active peptic ulcer disease.
• Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications.
• Pregnancy or breast-feeding.
• Active infections.
• Serological evidence of infection with HIV, or HBsAg or HCVAb positive within the previous 12 months prior to transplantation.
• Negative screen for Epstein-Barr Virus (EBV) by an EBNA method
• Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening.
• Schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medications.
• Ongoing substance abuse; drug or alcohol.
• Recent history of noncompliance.
• Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.