A Phase 3 Single Center Study of Islet Transplantation in Non-uremic Diabetic Patients

Prior treatment

• Panel reactive anti-HLA antibodies\> 50% by flow cytometry
• International normalized ratio \>1.5 and long term anticoagulant therapy
• Chronic corticosteroid use

Other illness

• Active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB)
• Any history of malignancy except resected squamous or basal cell carcinoma
• Clinically significant coronary artery disease
• Gastrointestinal disorders interfering with ability to absorb oral medications

Lab values

• HbA1c \> 10%
• Calculated glomerular filtration rate (GFR) \< 80mL/min for transplant-naïve patients (using subjects serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration equation CKD-EPI) or 50mL/min for previously transplanted patients currently on immunosuppression
• Macroalbuminuria \>300 mg/g creatinine
• Uncontrolled hyperlipidemia (LDL cholesterol \>130 mg/dL and/or triglycerides \>200 mg/dL)

Other

• Body mass index (BMI) \> 30
• Insulin requirement of \> 1.0 IU/kg/day
• For female subjects: positive pregnancy test, breast feeding or unwillingness to use effective contraceptive measures for the duration of the study.
• Negative Epstein-Barr Virus (EBV) by IgG
• Alcohol or substance abuse
• Baseline Hb below the lower limit of normal
• Elevated liver function tests \>1.5 times upper limit of normal
• Symptomatic cholecystolithiasis

• Male and female patients age 18-65 years of age at consent
• Ability to provide written informed consent
• Mentally stable and able to comply with the procedures of the study protocol
• Patients with T1D and insulin-dependent for at least 5 years fulfilling the following criteria:
  • Absent stimulated c-peptide (\<0.3 ng/mL) in response to a mixed meal tolerance test (MMTT; ensure 6 mL/kg body weight to a maximum of 360mL) measured at 60 and 90 min after the start of consumption
  • Patients who have been followed by a qualified physician for diabetes management for a minimum of 12 months
  • At least one episode of severe hypoglycemia in the past 12 months
  • A Clarke score of 4 or more defining reduced awareness of hypoglycemia
• Or, previous islet cell transplant recipients who have returned to partial or full insulin usage and are taking maintenance immunosuppression medications.