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 is individuals with type 1 diabetes, normal kidney function, and intractable hypoglycemia. All studies treated participants with up to 3 separate infusions of islets. Subjects in CIT07, a single arm Phase 3 license-enabling study, received induction and maintenance immunosuppression in an open-label fashion consisting of rabbit anti-thymocyte globulin (ATG; basiliximab instead of ATG for the 2nd and 3rd transplants, if applicable), etanercept, sirolimus and low-dose tacrolimus.

The study aimed to determine the safety and efficacy of islet transplantation when combined with an immunosuppressive medication regimen in treating patients with type 1 diabetes and hypoglycemia unawareness.

The primary outcome measure was the proportion of participants with an absence of severe hypoglycemic events and HbA1c less than 7.0%, assessed at 1 year after the first islet infusion. Secondary outcome measures included reduction in insulin requirements, mean amplitude of glycemic excursions, the incidence and severity of adverse events, and quality of life.

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
• 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 12 months prior to study enrollment
• Reduced awareness of hypoglycemia.

Exclusion criteria are documented in the study protocol.

Transplanted purified human pancreatic islets (PHPI) provided glycemic control, restoration of hypoglycemia awareness, and protection from severe hypoglycemic events (SHEs) in subjects with intractable impaired awareness of hypoglycemic (IAH) and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.

Data associated with the primary publication only are available on the Immune Tolerance Network Trial Share website through the following link: CIT-07 Public Data