Strategies to Improve Islet Survival
|Type 1 Diabetes Mellitus||Procedure: Islet transplant Drug: Antithymocyte globulin Drug: Basiliximab Drug: Lisofylline Drug: Sirolimus Drug: Tacrolimus||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Strategies to Improve Long Term Islet Graft Survival|
- Proportion of participants with insulin independence [ Time Frame: 75 days after first transplant infusion ]
- Reduction in insulin requirements, HbA1c, mean amplitude of glycemic excursions (MAGE), glycemic lability index (LI), Ryan hypoglycemia severity (HYPO) score, fasting glucose, glucose variation, beta score [ Time Frame: 75 days and 1 year following the first and final infusion ]
- Quality of life measures [ Time Frame: 75 days and 1 year following the first and final infusion, and 2 years after the final infusion ]
|Study Start Date:||December 2006|
|Study Completion Date:||February 2014|
|Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
Experimental: Islet Transfusion and LSF
Participants assigned to this group will receive an islet transfusion and an immunosuppressive medication regimen containing LSF.
Procedure: Islet transplant
Transplantation of pancreatic islet cellsDrug: Antithymocyte globulin
Immunosuppressive that selectively depletes activated T-cells and depletes resting T-cells in a dose-dependent manner.Drug: Basiliximab
Will replace antithymocyte globulin in all islet transplantations after the first oneDrug: Lisofylline
An anti-inflammatory that may reduce the rate at which islet cells die.Drug: Sirolimus
Maintenance immunosuppressive therapyDrug: Tacrolimus
Maintenance immunosuppressive therapy
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 for long-term survival in individuals with type 1 diabetes; however, it does not guarantee constant normal blood sugar control. As a result, 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 lisofylline (LSF). 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 assigned to this study will receive LSF. Participants in this study will receive up to three separate islet transplants and a regimen of immunosuppressive medications including antithymocyte globulin (ATG) for the first transplant, sirolimus, tacrolimus, and LSF to support the engrafting of the islets into the beta-cell mass. All participants will begin receiving ATG and sirolimus 2 days prior to transplantation. ATG will be continued until 2 days post-transplant. Sirolimus will be continued for the duration of the study. All participants will also receive tacrolimus starting one day post-transplant and continuing for the duration of the study. Basiliximab will be used in place of ATG with all subsequent transplants. Participants in the LSF group will begin to receive LSF one day prior to transplant and will continue to receive LSF until 5 days post-transplant. Transplantations will involve an inpatient hospital stay and infusion of islets into a branch of 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. 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 filtration rate (GFR) testing will occur at some visits. Participants will also test their own blood glucose levels at least five times per day throughout the study. A 24-month follow-up period will take place after the participant's last transplant.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00464555
|United States, Florida|
|University of Miami|
|Miami, Florida, United States|
|United States, Illinois|
|University of Illinois at Chicago|
|Chicago, Illinois, United States, 60607|
|Study Chair:||Camillo Ricordi, MD||Department of Surgery, University of Miami Miller School of Medicine - Diabetes Research Institute|