Efficacy of Islet After Kidney 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 assess the benefit of islet transplantation in type 1 diabetic (T1D) kidney transplant recipients.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients: Efficacy of Islet After Kidney Transplantation|
- Proportion of patients w/HbA1c </= to 6.5% and an absence of severe hypoglycemic events or a reduction in HbA1c of at least 1 point and an absence of severe hypoglycemic events [ Time Frame: At 1 year after first islet infusion ] [ Designated as safety issue: Yes ]
- Reduction in insulin requirements, HbA1c, MAGE, LI, HYPO score, fasting glucose, beta score, serum creatinine, c-peptide levels, MMTT, Clarke Survey, FSIGT, CGMS, number of hypoglycemic events, renal impact, cardiovascular impact, and quality of life [ Time Frame: At 1 year after first islet infusion and/or 1 year after final islet infusion ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2007|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Islet transplant
Up to three separate islet transplants will occur and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG) and etanercept throughout study. Participants will begin receiving ATG 2 days prior to the initial islet transplant and will continue to receive ATG until Day 2 post-transplant. Daclizumab or Basiliximab will be used for subsequent transplants. Etanercept will be given on the day of transplant and on Days 3, 7, and 10 post-transplant.
Biological: Islet transplant
200 ml suspension of allogenic human purified islets
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 and thus kidney transplant. 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. The purpose of this study is to assess the benefit of islet transplantation in type 1 diabetic kidney transplant recipients.
Participants in this study will be type I diabetics who have received a kidney transplant for ESRD.. If subjects have not received ITT in the 12 months prior to enrollment, they must undergo a period of standardized diabetes care by an experienced diabetologist at the transplant center using the current ADA's standards of medical care in diabetes. Throughout the study, all participants will remain on the immunosuppressive therapy intended for their kidney. Participants will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG) and etanercept. They will begin receiving ATG 2 days prior to transplant and will continue to receive ATG until Day 2 post-transplant. Etanercept will be given on the day of transplant and on Days 3, 7, and 10 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 30 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 30 days after the second transplant and who show partial graft function will be considered for a third islet transplant. Daclizumab 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 will enter a reduced follow-up period.
There will be approximately 15 study visits. 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, and urine collection will occur at some visits. Participants will also test their own blood glucose levels throughout the study. A 36-month follow-up period will take place after the participant's last transplant, consisting of 8 additional visits.
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94143|
|United States, Florida|
|University of Miami|
|Miami, Florida, United States|
|United States, Georgia|
|Atlanta, Georgia, United States|
|United States, Illinois|
|Chicago, Illinois, United States|
|University of Illinois at Chicago|
|Chicago, Illinois, United States, 60607|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States|
|United States, Wisconsin|
|University of Wisconsin|
|Madison, Wisconsin, United States, 53792|
|University of Alberta|
|Edmonton, Alberta, Canada|
|Principal Investigator:||James F. Markmann, MD, PhD||Massachusetts General Hospital|