Allogeneic Islet Cells Transplanted Onto the Omentum

Prior treatment

• Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection within one year prior to study enrollment.
• Chronic use of systemic steroids, except for the use of ≤5 mg prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only.
• Treatment with any anti-diabetic medications other than insulin within 4 weeks of enrollment.
  • 23\. Use of any investigational agents within 4 weeks of enrollment. 24. Administration of live attenuated vaccine(s) within 2 months of enrollment. 25. Any medical condition that, in the opinion of the investigator, will interfere with the safe participation in the trial.
  • 26\. Treatment with any immunosuppressive regimen at the time of enrollment. 27. A previous islet transplant. 28. A previous pancreas transplant 29. Inflammatory bowel disease. 30. History of intestinal obstructions. 31. Previous major abdominal surgery. 32. History of peritonitis.

Other illness

• Presence or history of panel-reactive anti-HLA antibodies.
• Presence or history of active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB).
• Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
• A history of Factor V deficiency.
• Any coagulopathy or medical condition requiring long-term anticoagulant therapy.
• Symptomatic peptic ulcer disease.
• Gastrointestinal disorders potentially interfering with the ability to absorb oral medications.

Lab values

• HbA1c \>10%.
• Presence or history of macroalbuminuria (\>300mg/g creatinine).
• For female subjects: Serum or urine Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. If sexually active, subject must use at least two medically accepted methods of birth control.
• Hb below the lower limits of normal at the local laboratory; lymphopenia (\<1,000/µL), neutropenia (\<1,500/µL), or thrombocytopenia (platelets \<100,000/µL).
• Severe co-existing cardiac disease,
  • recent myocardial infarction (within past 6 months)
  • evidence of ischemia on functional cardiac exam within the last year) left ventricular ejection fraction \<30%.
• Hyperlipidemia despite medical therapy (fasting LDL cholesterol \> 130 mg/dL, fasting triglycerides \> 200 mg/dl).

Other

• Body Mass Index (BMI) \>30 kg/m2 or patient weight ≤50 kg.
• Insulin requirement of \>1.0 IU/kg/day or \<15 U/day.
• Untreated proliferative diabetic retinopathy.
• Blood Pressure: SBP \>160 mmHg or DBP \>100 mmHg.
• Glomerular filtration rate \<80 mL/min/1.73 m2 (calculated).
• Negative screen for Epstein-Barr Virus (EBV) by IgG determination.
• Active alcohol or substance abuse.
• Persistent elevation of liver function tests at the time of study entry.
• Symptomatic cholecystolithiasis.
• Acute or chronic pancreatitis.

• Male and female patients age 18 to 65 years of age.
• Ability to provide written informed consent.
• Mentally stable and able to comply with the procedures of the study protocol.
• Type1 diabetes with onset of disease at \<40 years of age, insulin-dependence for \> 5 years at the time of enrollment
• Absent stimulated c-peptide (\<0.3ng/mL) in response to a mixed meal tolerance test.
• Involvement in intensive diabetes management
• At least one episode of severe hypoglycemia in the 12 months prior to study enrollment.
• Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more OR A Hypoglycemia score greater than or equal to the 90th percentile (1047) during the screening period; OR Marked glycemic lability and defined by a lability index score greater than or equal to the 90th percentile (433 mmol/L2/h•wk-1) during the screening period; OR A composite of a Clarke score of 3 or less and a hypoglycemia score greater than or equal to the 75th percentile (423) and a lability index greater than or equal to the 75th percentile (329) during the screening period.
• Subjects screening data from 20053135 protocol will be accepted for subjects eligible for this study. If 20053135 visit was 12 months prior to enrollment, Visit 2 laboratory should be repeated.