Pancreatic Islet Cell Transplantation After Kidney Transplantation - A Novel Approach to Immunosupression

1. Patient has been fully informed and has signed an IRB approved informed consent form and is willing and able to follow study procedures for the full 24 months.
2. Type 1 diabetes mellitus of more than 5 years duration
3. Age between 18 and 65

4. Unstable diabetes mellitus control despite expert management by a diabetology care team for at least 6 months prior to consideration for transplantation as defined by the following:

   • During the past six months (or during the period of intensive diabetes care): Any episodes of hypoglycemic unawareness, as defined by the inability to recognize glucose levels below 50 mg/dL; or episodes of loss of cognitive function; or frequent episodes of symptomatic hypoglycemia; or admission to the hospital for hypo- or hyperglycemia; and
   • HbA1C>6.5%.
5. Patient underwent kidney transplantation at least six months before enrollment, and has stable kidney allograft function, defined as creatinine levels of maximum 2 mg/dl, stable renal allograft function as assessed by the transplant nephrologist, and has a creatinine clearance of more than 40 ml/min.
6. Psychogenically able to comply, in the opinion of the investigator
7. Female patients of childbearing potential must have a negative urine or serum pregnancy test upon hospitalization or within 7 days prior to enrollment and have agreed to utilize effective birth control throughout the study as well as for 6 weeks following study completion

Exclusion Criteria:

• Patient has previously received or is receiving an organ or bone marrow transplant other than a first kidney transplant.

  2. Patient has a known hypersensitivity to Tacrolimus, Sirolimus, Alemtuzumab, or Mycophenolate (allow substitution of Myfortic for CellCept).
  3. Patient is pregnant or lactating (must provide effective contraception method).
  4. Patient has participated in a blinded trial or participated in a trial involving a non-marketed (investigational) drug within 3 months of enrollment.
  5. Patient has participated in a trial involving a marketed drug or an infusion device within 30 days of the start of the trial.
  6. Patient exhibits any one of the following clinical criteria:
  • Creatinine clearance or Glofil test \< 40 mL/min
  • Serum creatinine > 2.0 mg/dL consistently, or more than 0.2 mg/dl increase in creatinine over the last five months
  • Body mass index > 28
  • Malignancy other than BCC and SCC
  • Radiographic evidence of pulmonary infection
  • Evidence of liver disease as evidenced by >2X ULN for AST, ALT, Alk. Phos., or T. bili.
  • Active infections
  • Hypercoagulable states (history of recurrent venous thrombosis, defined thrombophilia)
  • Bleeding / coagulation disorders
  • Basal C-peptide > 0.3 ng/mL
  • HbA1C >12%
  • Insulin requirement > 1 IU/kg/day
  • Seropositivity for HIV, HBV, HCV, HTLV-I
  • Abnormal Pap smear, active gynecological infection
  • Positive exercise or chemical cardiac tolerance test
  • Patients currently under treatment for a medical condition requiring chronic use of steroids at a dose of prednisone >10 mg/day will be excluded.
  • Substance/alcohol abuse
  • Untreated proliferating diabetic retinopathy
  • PPD conversion or positive PPD without INH if suspicious TB by chest X-ray or symptoms
  • No primary care physician or primary care physician less than 6 months
  • Smoking in the last 6 months
  • Abnormal CBC / Hemoglobin \< 10 g/dL
  • Microalbuminuria > 300 mg/24 hrs
  • Untreated hyperlipidemia - TC > 200 mg/dL, TGC > 200 mg/dL, LDL > 130 mg/dL
  • Untreated hyponatremia, hypokalemia, hypercalcemia, hypocalcemia
  • Iodine contrast allergy
  • PSA > 4 ng/mL
  • PRA > 20%
  • Active peptic ulcer disease/gallstones/hemangioma
  • Abnormal mammogram.
  • Patient receives any of the prohibited medications