Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients: Efficacy of Islet After Kidney Transplantation (CIT-06/08)

General Description

The CIT consortium conducted a total of 9 studies across North America (CIT02 through CIT08) and the Nordic region (CIT01). CIT08 was a long-term follow-up study for interested participants at the North American sites. The target population was individuals with type 1 diabetes, normal kidney function, and intractable hypoglycemia. All studies treated participants with up to 3 separate infusions of islets. Unlike the other studies, subjects in CIT06 had previously received a kidney transplant and were receiving maintenance immunosuppression. CIT06 was a single arm Phase 3 license-supporting study. At the time of islet transplant, subjects in CIT06 received induction therapy in an open-label fashion with rabbit anti-thymocyte globulin (ATG, 5 doses; daclizumab or basiliximab instead of ATG for the 2nd and 3rd transplants, if applicable) and etanercept. Subjects remained on their calcineurin-based maintenance immunosuppression regimen already in place for their renal allograft.

Objectives

CIT-06: The primary objective is to test the hypothesis that islet transplantation in patients with established kidney transplants leads to a reduced risk of diabetes-related complications as assessed by improved metabolic control measured by serial HbA1c levels and/or reduced occurrence of hypoglycemic events compared with IIT. Secondary objectives of this study will assess whether successful islet transplantation leads to improved QOL, improved metabolic control and reduced risk of cardiovascular and renal complications from diabetes.

CIT-08: The primary objective is to provide extended follow-up for safety and efficacy and to support continued islet graft function to participants previously enrolled in CIT02, CIT03, CIT04, CIT05, CIT06, or CIT07.

Outcome Measure

The primary outcome measure was the proportion of participants with an absence of severe hypoglycemic events and either a reduction in HbAc1 of at least 1 point or HbAc1 of at most 6.5%, assessed at 1 year after the first islet transfusion. Secondary outcome measures included reduction in insulin requirements, mean amplitude of glycemic excursions, renal and cardiovascular impact, and quality of life.

Criteria

Individuals who met the following criteria were eligible for enrollment:

• Clinical history compatible with type 1 diabetes with onset at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28
• Absent stimulated C-peptide (less than 0.3 ng/mL) 60 and 90 minutes post-mixed-meal tolerance test
• Received kidney transplant for ESRD and are taking appropriate calcineurin inhibitor (CNI)-based maintenance immunosuppressive therapy
• Stable renal function (defined as creatinine of no more than one-third greater than the average creatinine determination performed in the 3 previous months prior to islet transplantation)
• Intensive diabetes management followed by reduced awareness of hypoglycemia or HbAc1 ≥ 7.5%.

Exclusion criteria are documented in the study protocol.

Outcome

The study has concluded.