Peritransplant Deoxyspergualin in Islet Transplantation in Type 1 Diabetes
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

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 safety and efficacy of deoxyspergualin (DSG), an immunosuppressant drug, on
      post-transplant islet function in people with type 1 diabetes who have not responded to
      intensive insulin therapy.
    

Detailed description: 
      Type 1 diabetes, also known as insulin-dependent diabetes, is a chronic disease in which the
      pancreas produces insufficient insulin to properly regulate blood sugar levels. Hypoglycemia,
      low blood sugar, and hyperglycemia, high blood sugar, can lead to significant complications
      in people with type 1 diabetes. Intensive insulin therapy has been shown to reduce the risk
      of chronic complications in people who achieve near normalization of glycemia. However, this
      therapy is labor intensive, difficult to implement, and associated with an increased
      frequency of severe hypoglycemia. Transplantation of islets from a healthy pancreas has been
      successful in restoring normal blood sugar levels and has led to initial insulin independence
      in people with type 1 diabetes. Rejection of these islets by the recipient's immune system,
      however, makes the treatment ineffective within a couple of years. Immunosuppressant drugs
      may be an effective way to maintain islet function post-transplant. The purpose of this study
      is to assess the safety and efficacy of an immunosuppressive regimen that includes DSG on
      post-transplant islet function in people with type 1 diabetes who have not responded to
      intensive insulin therapy. The study will also seek to improve the understanding of
      determinants of success and failure of islet transplants for type 1 diabetes.

      Following screening procedures and 2 days prior to islet transplant, participants will be
      randomly assigned to either this Phase 2 trial or a multicenter Phase 3 trial. Participants
      in this study will receive up to three separate islet transplants. They will begin receiving
      antithymocyte globulin (ATG) and sirolimus 2 days prior to the first islet transplant. ATG
      will continue to be given until Day 2 post-transplant. Participants will continue taking
      sirolimus for the duration of the study. On the day of transplant, participants will receive
      DSG and etanercept, in addition to ATG and sirolimus. The DSG infusion will be administered
      over 3 hours and will immediately precede the islet transplant. Participants will continue
      receiving daily 3-hour infusions of DSG through Day 6 post-transplant. Etanercept will also
      be administered on Days 3, 7, and 10 post-transplant. Tacrolimus will be administered on Day
      1 post-transplant and continued throughout the study.

      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 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 up to 21 study visits following each transplant. A physical exam, review of
      adverse events, blood collection, urine tests, and measures of immunosuppression levels will
      occur at most visits. An abdominal ultrasound and glomerular filtration rate testing will
      occur at some study visits. Participants will also self-test their glucose levels at least
      five times per day throughout the study. A 12-month follow-up period will take place after
      the participant's last transplant.
    

Intervention name(s): Allogeneic Pancreatic Islet Cells; Deoxyspergualin; Antithymocyte globulin; Daclizumab or basiliximab; Sirolimus; Tacrolimus; Etanercept
Intervention type(s): Biological; Drug; Biological; Biological; Drug; Drug; Biological
Intervention description(s): Preparation of allogeneic pancreatic islet cells injected into the portal vein of the liver; An anti-inflammatory agent that blocks proinflammatory cytokine production and inhibits T-cells and B-cells and affects antigen presenting cells.; Immunosuppressive that selectively depletes activated T-cells and depletes resting T-cells in a dose-dependent manner.; Will replace antithymocyte globulin in all islet transplantations after the first one; Maintenance immunosuppressive therapy; Maintenance immunosuppressive therapy; Blocks TNF-alpha which is toxic to islet cells
Intervention MeSH terms: Gusperimus; Sirolimus; Etanercept; Tacrolimus; Antilymphocyte Serum; Basiliximab; Daclizumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Insulin dependence; Hypoglycemia; Hyperglycemia unawareness