Strategies to Improve Long Term Islet Graft Survival and Extended Follow Up after Islet Transplantation in Type 1 Diabetes (CIT-02/08)

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. The CIT02 protocol focused on treating islets pre-transplant, and subjects were randomized to receive islets prepared with either Lisofylline or Exenatide. For induction and maintenance immunosuppression, the subjects received rabbit anti-thymocyte globulin (ATG; basiliximab instead of ATG for the 2nd and 3rd transplants, if applicable), etanercept, sirolimus, and tacrolimus in an open-label fashion.

Objectives

CIT-02: The primary objective is to determine the proportion of subjects who are insulin independent after a single islet transplant at 75 +/- 5 days post-transplant in subjects treated with Lisofylline added to a standard islet transplant regimen who enroll at the same sites as the CIT-02 subjects.

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 insulin independence at 75 days following the first transplant infusion. Secondary outcome measures included reduction in insulin requirements, mean amplitude of glycemic excursions, HbA1c levels, and assessment of quality of life.

Criteria

Individuals who met the following criteria were eligible for the study:
- 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
- Involvement of intensive diabetes management, defined as: (1) Self-monitoring of glucose values no less than a mean of three times each day averaged over each week; (2) Administration of three or more insulin injections each day or insulin pump therapy; (3) Under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least three evaluations during the 12 months prior to study enrollment
- At least one episode of severe hypoglycemia in the past 12 months prior to study enrollment
- Reduced awareness of hypoglycemia. More information about this criterion, including specific definition of hypoglycemia unawareness, is in the protocol

Exclusion criteria are documented in the study protocol.

Outcome

This study has been concluded, but results have not yet been published.