Islet Transplantation in Type 1 Diabetic Patients Using the University of Illinois at Chicago (UIC) Protocol

• Safety: Incidence and severity of events related to islet infusion, immunosuppression, and islet preparations [ Time Frame: One year after first and last islet transplants ] [ Designated as safety issue: Yes ]
  
• The proportion of subjects with an HbA1c ≤ 6.5% and free of severe hypoglycemic events [ Time Frame: One year after first and last islet transplants ] [ Designated as safety issue: Yes ]
  

• Insulin independence [ Time Frame: One year after the last transplant ] [ Designated as safety issue: No ]
  
• Hypoglycemic episodes by HYPO score [ Time Frame: One year after the last transplant ] [ Designated as safety issue: No ]
  
• Glucose variability and hypoglycemia duration [ Time Frame: One year after the last transplant ] [ Designated as safety issue: No ]
  

This study is a Phase 3 single center, uncontrolled trial in which 1-3 allogeneic pancreatic islet transplants are performed for each study subject. Follow-up evaluations after transplant continue for 52 weeks after the final islet transplantation. Thereafter, subjects may enroll for a 5-year follow-up study to evaluate the function of the islets and to measure and regulate immunosuppressive drug levels and side effects.

The safety of islet transplantation depends primarily on the incidence of serious and unexpected complications or adverse events and the ability of the cell isolation laboratory to produce uncontaminated islet cell preparations with minimal endotoxin content.

All study subjects are followed for safety for one year. An independent Data Monitoring Committee (DMC), composed of 3 members who have training in medicine and/or organ transplantation, will review eligibility and safety data within 2 weeks after each islet transplantation and every two months thereafter. An independent monitor, who is knowledgeable about Good Clinical Practice(GCP)guidelines and regulations, monitors the study for compliance with 21 CFR and according to ICH GCP Guidelines. Within the Clinical Research Center, representatives of the Scientific Advisory Committee and the Research Subject Advocacy Program monitor safety. These entities report to the UIC Institutional Review Board (IRB), which also reviews safety data annually and on occurrence of serious adverse events. The principal investigator also reports serious adverse events to the US Food and Drug Administration(FDA).

Success: Islet transplantation is considered a success when subjects do not use insulin, and they achieve a fasting glucose level not exceeding 140 mg/dL more than three times in a week, and not exceeding two-hour post-prandial values of 180 mg/dL more than four times in a week.

Partial Success: Subjects who have a reduction in insulin requirements but who do not achieve insulin independence and present with a reduction in HbA1c and number of hypoglycemic episodes are considered to have partial success of islet transplantation. Reduction in insulin-requirements are assessed by comparing the pre-transplant insulin requirement recorded over two consecutive days (expressed as insulin units per kg) with the requirement on the two consecutive days preceding the subsequent islet infusion, and the requirements on two consecutive days at six months and again on two consecutive days at one year after the final transplant.

Failure: Absence of measurable levels of C-peptide after transplantation is considered as failure of islet cell transplantation.