Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients: Efficacy of Islet After Kidney Transplantation (CIT-06)
Study Design: Clinical Trial
Conditions: Diabetes Mellitus, Diabetes Mellitus, Type 1
Duration: 2008 – Present
# Recruitment Centers: 10
Treatment: Islet Transplantation
Available Genotype Data: No
Image Summary: No
Transplant Type: Kidney Transplant
Does it have dialysis patients: No
Access to samples for Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients: Efficacy of Islet After Kidney Transplantation (CIT-06) 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 Efficacy of Islet after Kidney Transplantation (CIT-06) study is a prospective, multicenter, single-arm clinical trial that was conducted by the CITC to investigate the safety and efficacy of islet transplantation in type 1 diabetic kidney transplant recipients. Individuals with type 1 diabetes who had received a kidney transplant for ESRD and showed reduced awareness of hypoglycemia were eligible for enrollment. 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), received from 2 days prior to transplant until 2 days post-transplant, and etanercept, received on the day of transplant and on Days 3, 7, and 10 post-transplant. In addition to these medications, participants remained on the immunosuppressive therapy intended for the kidney transplant throughout the study. Participants who did not achieve or maintain insulin independence by Day 30 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 30 days following the second transplant were considered for a third islet transplant. Daclizumab 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 36 months after the participant’s last transplant.
The study aimed to determine the safety and efficacy of islet transplantation in type 1 diabetes patients who received a kidney transplant.
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.
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.
This study is ongoing.