Islet Transplantation in Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; 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
      determine the safety and effectiveness of islet transplantation, combined with
      immunosuppressive medications, for treating type 1 diabetes in individuals experiencing
      hypoglycemia unawareness and severe hypoglycemic episodes.
    

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. 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,
      transplantation of pancreatic islets is a possible treatment option. 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 determine the safety
      and efficacy of islet transplantation, when combined with an immunosuppressive medication
      regimen, for treating 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 a site-specific Phase 2
      islet transplantation study. 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 low-dose tacrolimus.

      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 up to 19 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 five times per day throughout the study. A
      24-month follow-up period will take place after the participant's last transplant.
    

Intervention name(s): Allogeneic Pancreatic Islet Cells; Antithymocyte Globulin; Sirolimus; Tacrolimus; Etanercept; Islet Transplantation; Basiliximab
Intervention type(s): Biological; Biological; Drug; Drug; Biological; Procedure; Biological
Intervention description(s): 200 ml suspension of allogenic human purified islets; Participants will begin receiving ATG 2 days prior to the first islet transplant. ATG will continue to be given until Day 2 post-transplant.; Participants will begin receiving sirolimus 2 days prior to the first islet transplant and will be given for the duration of the study.; On Day 1 post-transplant, participants will receive tacrolimus, which will also be taken for the duration of the study.; Etanercept will be taken on the day of transplant and Days 3, 7, and 10 post-transplant.; Transplantation of pancreatic islet cell; Basiliximab will be used in place of ATG for the second and third transplants, if they are necessary.
Other intervention name(s): Rapamycin; FK-506; Fujimycin; chimeric mouse-human antiCD25; Ig gamma-1 chain C region
Intervention MeSH terms: Sirolimus; Etanercept; Tacrolimus; Antilymphocyte Serum; Basiliximab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Insulin dependence; Hypoglycemia; Hypoglycemia unawareness