B-Lymphocyte Immunotherapy in Islet Transplantation: Toward Calcineurin-Inhibitor Free Immunosuppression (CIT-0501)
Study Design: Clinical Trial
Conditions: Diabetes Mellitus, Diabetes Mellitus, Type 1
Duration: 2008 – 2011
# Recruitment Centers: 1
Treatment: Immunosuppressive medication regimen containing rituximab
Available Genotype Data: No
Image Summary: No
Transplant Type: Islet Cell Transplant
Does it have dialysis patients: No
Access to samples for B-Lymphocyte Immunotherapy in Islet Transplantation: Toward Calcineurin-Inhibitor Free Immunosuppression (CIT-0501) is currently only available via collaboration. Please contact the parent study to ask about ancillary study opportunities.
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 Strategies to Improve Islet Survival (CIT-05) study is a prospective, 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 containing rituximab. Individuals 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 CIT-05 study or a Phase 3 islet transplantation study being conducted by the CITC (CIT-07). Participants received up to three separate islet transplants and a regimen of immunosuppressive medications to support the engrafting of the islets into the beta-cell mass. The medication regimen included antithymocyte globulin (ATG), sirolimus, and rituximab 2 days prior to transplant. ATG was given until day 2 post-transplant, and additional rituximab was given on days 5 and 12 post-transplant. Treatment with sirolimus was continued for the duration of the study. 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. Either daclizumab or 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 at least five times daily throughout the study. Subjects were followed for 24 months after the participant’s last transplant.
This study was terminated for lack of efficacy.
The study aimed to determine the safety and efficacy of islet transplantation when combined with an immunosuppressive medication regimen containing rituximab.
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, incidence of immune sensitization (defined by detected anti-HLA antibodies not present prior to transplantation), 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.
This study was terminated for lack of efficacy.