• Safety - will be evaluated by the incidence, grade, and type of adverse events, changes in laboratory parameters, evaluation of the implant site and physical exams.
  

• Efficacy - will be assessed by:
  
• Blood glucose levels
  
• Daily glycemic excursions
  
• Pre-prandial glucose levels
  
• Post-prandial glucose levels
  
• Glucose responses from OGTT (mg/dL and AUC:glucose
  
• Stimulated C-peptide levels from OGTT (ng/mL and
  
• AUC:C-Peptide
  
• HbA1c (%)
  
• Insulin requirements (units/day)
  
• Arginine stimulation tests
  
• Numbers of hypoglycemic and hyperglycemic episodes
  
• Functional duration - will be determined by stimulated C-peptide from OGTT.
  

Allogeneic Cultured Islet Cells (human, Novocell); Encapsulated in Polyethylene Glycol; Administered Subcutaneously are a combination biologic and device product in which the pharmacologically active agent is human insulin that is released from the functional islet cells by natural production and release, stimulated by control mechanisms in response to blood glucose concentrations. The device component is a uniform and conformal polymer coating around each islet. Islet cells are isolated from multiple human pancreases procured from human organ donors who meet a specific human donor profile established by the UNOS and the FDA’s requirements for Good Tissue Practices. Because the pancreases used for islet cell isolation are not intended for whole-organ transplantation, specific procurement, surgical removal, packaging and shipping protocols are provided by Novocell, Inc. to the Organ Procurement Organizations.

The primary outcome is demonstration that encapsulated islet allografts can be implanted safely in the subcutaneous tissues without the use of long-term immunosuppression. The expected functional outcomes from the implantation of the encapsulated islets are significant reductions in the average blood glucose daily glycemic excursions and in insulin requirements as well as significant increases in C-peptide levels in response to meal challenges. The ultimate expected outcome is that patients who receive these implants will have reduced hemoglobin A1c levels that may be associated with reduced long-term diabetic complications. An important outcome should be reduction in hypoglycemic episodes and crises with significantly functioning grafts without having the risks associated with hepatic portal vein infusion and long-term immunosuppression.