Islet Transplantation in Type 1 Diabetes (CIT-07)
Study Design: Clinical Trial
Conditions: Diabetes Mellitus, Diabetes Mellitus, Type 1
Duration: 2008 – 2017
# Recruitment Centers: 8
Treatment: Islet Transplantation
Available Genotype Data: No
Image Summary: No
Transplant Type: Islet Cell Transplant
Does it have dialysis patients: No
Hypoglycemia unawareness, a condition characterized by reduced or absent warning signals for hypoglycemia, is a life-threatening complication of type 1 diabetes that may be developed by some patients. For such individuals, common treatment includes pancreatic islet transplantation; however, rejection of these islets by the recipient’s immune system lessens the efficacy of the treatment over time. In response to the need for new strategies to improve clinical outcomes among recipients, the Clinical Islet Transplantation Consortium CITC , a network of clinical centers and a data coordinating center, was established in 2004 to conduct studies focused on improving the safety and long-term success of islet cell transplantation.
The Islet Transplantation in Type 1 Diabetes (CIT-07) study is a prospective, multicenter, single-arm clinical trial that was conducted by the CITC to investigate the safety and efficacy of islet transplantation when combined with an immunosuppressive medication regimen for treating type 1 diabetes in individuals with hypoglycemia unawareness. Individuals with type 1 diabetes with type 1 diabetes, dependence on insulin for at least 5 years at study entry, and at least one episode of severe hypoglycemia in the past 12 months were eligible for enrollment. Eligible participants were randomly assigned to either the Phase 3 CIT-07 trial or a site-specific Phase 2 islet transplantation study investigating specific immunosuppressive agents. Participants in the CIT-07 study received up to three separate islet transplants and a regimen of immunosuppressive medications, including antithymocyte globulin (ATG), sirolimus, and tacrolimus, to support the engrafting of the islets into the beta-cell mass. Participants who did not achieve or maintain insulin independence by Day 75 post-transplant were considered for a second islet transplant, and participants who showed partial graft function and who remained dependent on insulin for longer than 1 month following the second transplant were considered for a third islet transplant. Basiliximab was used in place of ATG for the second and third transplants, if necessary.
Following each transplant, study visits were conducted to perform a physical exam, review adverse events, and collect blood samples and information on quality of life. Participants were required to test their blood glucose levels throughout the study. Subjects were followed for 24 months after the participant’s last transplant.
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 HbAc1 less than 6.5%, 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