Efficacy of Islet After Kidney Transplantation
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Islet transplantation; Antithymocyte Globulin; Daclizumab or Basiliximab; Etanercept; Allogenic human purified pancreatic islets
Intervention type(s): Procedure; Biological; Biological; Biological; Biological
Intervention description(s): 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.; 200 ml suspension of allogenic human purified islets
Other intervention name(s): ATG
Intervention MeSH terms: Etanercept; Antilymphocyte Serum; Basiliximab; Daclizumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hypoglycemia; Kidney Transplant; Insulin independence; Islet Transplantation; Intensive Insulin Therapy