B-Lymphocyte Immunotherapy in Islet Transplantation
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with the immunosuppressive medications and medications to support islet survival for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.
Type 1 Diabetes Mellitus
Biological: Allogeneic Pancreatic Islet Cells
Biological: Antithymocyte globulin
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||B-Lymphocyte Immunotherapy in Islet Transplantation: Toward Calcineurin-Inhibitor Free Immunosuppression (CIT-05)|
- Insulin independence [ Time Frame: 75 days after a single islet transplant ] [ Designated as safety issue: No ]
- reduction in insulin requirements, HbA1c, MAGE, LI, HYPO score, fasting glucose, beta score, quality of life [ Time Frame: 75 days and 1 year following first and final infusion ] [ Designated as safety issue: No ]
|Study Start Date:||November 2006|
|Study Completion Date:||September 2011|
|Primary Completion Date:||September 2011 (Final data collection date for primary outcome measure)|
Experimental: Allogeneic Pancreatic Islet Cells
Participants will receive up to three islet transplants and maintenance immunosuppressive therapy.
Biological: Allogeneic Pancreatic Islet Cells
transplant of islet cells injected into the portal vein of the liverBiological: Antithymocyte globulin
Immunosuppressive that selectively depletes activated T-cells and depletes resting T-cells in a dose-dependent manner.
Other Name: ATGBiological: Daclizumab
Will replace antithymocyte globulin in all islet transplantations after the first one
Other Name: ZenapaxBiological: Rituximab
Depletes transient B-cells
Other Name: RituxanDrug: Sirolimus
Maintenance immunosuppressive therapy
Other Name: Rapamune
Type 1 diabetes is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with type 1 diabetes; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure. Some individuals with type 1 diabetes develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, pancreas or pancreatic islet transplantation are possible treatment options. Unfortunately, insulin independence among islet transplant recipients tends to decline over time. New strategies aimed at promoting engraftment of transplanted islets are needed to improve the clinical outcomes associated with this procedure. The purpose of this study is to determine the safety and efficacy of islet transplantation, when combined with an immunosuppressive medication regimen containing rituximab. This regimen is intended to treat type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes. This study will also seek to improve the understanding of determinants of success and failure of islet transplants for type 1 diabetes.
Eligible participants will be randomly assigned to this study or the Phase 3 islet transplantation study (DAIT CIT-07). Participants in this study will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG), sirolimus, and rituximab. They will begin receiving ATG, sirolimus, and rituximab 2 days prior to the first islet transplant. ATG will continue to be given until Day 2 post-transplant, and sirolimus will be given for the duration of the study. They will receive additional rituximab on Days 5 and 12 post-transplant.
Transplantations will involve an inpatient hospital stay and infusion of islets into the portal vein. Participants who do not achieve or maintain insulin independence by Day 75 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 1 month after the second transplant and who show partial graft function will be considered for a third islet transplant. Daclizumab or basiliximab will be used in place of ATG for the second and third transplants, if they are necessary. Participants who do not meet the criteria for a subsequent transplant and do not have a functioning graft will enter a reduced follow-up period.
There will be approximately 15 study visits following each transplant. A physical exam, review of adverse events, and blood collection will occur at most visits. A chest x-ray, abdominal ultrasound, electrocardiogram, quality of life questionnaires, urine collection, and glomerular filtrating rate (GFR) testing will occur at some visits. Participants will also test their own blood glucose levels at least four times per day throughout the study. A 12-month follow-up period will take place after the participant's last transplant.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00468442
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States|
|Study Chair:||Ali Naji, MD, PhD||University of Pennsylvania|