Steroid-free and Long-term Calcineurin-free Trial in Islet Cell Transplantation

Inclusion Criteria

Potential candidates must have type 1 diabetes mellitus and fulfill one or more of the following:

• Manifest signs and symptoms that are severe enough to be incapacitating. Incapacitating signs and symptoms include hypoglycemic episodes requiring assistance by others and hypoglycemia unawareness (the inability to recognize low blood glucoses; glucoses 8.0% but 65 years
• Duration of diabetes 6 months
• Body mass index > 26
• Weight > 80 kg
• Insulin requirement > 1.0 u/kg/d
• HbA1c > 12%
• Stimulated or basal C-peptide > 0.3 ng/ml
• Corrected creatinine clearance 300 mg/24 hours)
• Anemia (hemoglobin 130 mg/dl and/or fasting triglycerides > 200 mg/dl)
• Abnormal liver function tests (consistently > 1.5 x normal range)
• Serological evidence of HIV, HBsAg and/or HBcAb, HBsAb without history of vaccination, human t cell lymphotropic virus 1 (HTLV-1), or hepatitis C virus (HCV)
• Negative serology for Epstein-Barr virus (EBV) or evidence of acute or chronic infection (IgM ≥ IgG)
• Lack of updated immunizations per current Centers for Disease Control (CDC) guidelines (including lack of immunization against hepatitis B, pneumococcus and influenza - during season)
• Presence of panel reactive antibodies > 20%
• Prostate-specific antigen (PSA) > 4 ng/ml unless malignancy is ruled out
• Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis can be provided)
• X-ray evidence of pulmonary infection or other significant pathology
• Gall stones and/or portal hypertension and/or hemangioma on liver ultrasound
• Abnormal abdominal or pelvic ultrasound (evidence of masses that are considered suspicious for malignancy or adenopathy)
• Active peptic ulcer disease
• Active infections
• Unstable cardiovascular status (including positive stress echocardiography if age > 35)
• Untreated or unstable proliferative diabetic retinopathy
• Previous/concurrent organ transplantation (except for failed islet cell or pancreas transplantation)
• Malignancy or previous malignancy
• Any medical condition requiring chronic use of steroids
• Active alcohol or substance abuse; smoking in the last 6 months.
• Sexually active females who are not:
• post-menopausal,
• surgically sterile, or
• not using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices with spermicide are acceptable; condoms used alone are not acceptable)
• Positive pregnancy test or intent for future pregnancy, or male subject's intent to procreate
• Any condition or any circumstances that make it unsafe to undergo an islet cell transplant
• Psychogenically unable to comply
• Failed psychological evaluation
• Persistent leukopenia (white blood cell count < 3,000/uL on more than 3 occasions)