Safety and Effectiveness of Low Molecular Weight Sulfated Dextran in Islet Transplantation
Condition: Diabetes Mellitus, Type I
MeSH terms: 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 effectiveness of low molecular weight sulfated dextran (LMW-SD) on
      post-transplant islet function in people with type 1 diabetes who have responded to intensive
      insulin therapy.
    

Detailed description: 
      Type I 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,
      or low blood sugar, and hyperglycemia, or 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, can make the treatment ineffective. An immune response
      known as instant blood-mediated inflammatory reaction (IBMIR) results in the disruption of
      islet integrity and islet loss within an hour of transfusion. LMW-SD inhibits IBMIR by
      preventing the cascade that triggers it, when combined with pancreatic islets. The purpose of
      this study is to determine the safety and efficacy of LMW-SD given with islet transfusion and
      post-transfusion along with immunosuppressive therapy, including mycophenolate mofetil or
      sirolimus, tacrolimus or cyclosporine, and thymoglobulin or basiliximab, on the success of
      islet transplantation in people with type 1 diabetes.

      This study will last for 1 year after the final islet transplant. Participants may receive up
      to 3 islet transplants while participating in this study. Participants eligible for this
      study will have clinic visits every 6 months. Once a preparation of islets becomes available,
      participants will be randomly assigned to Arm 1 or Arm 2. Participants in Arm 1 will receive
      LMW-DS during and for 5 hours after infusion. Participants in Arm 2 will receive heparin at
      the time of infusion. In addition, all participants will receive anticoagulation prophylaxis
      agents consisting of Klexzane® (Enoxaparinsodium) and Trombyl® or Albyl-E® (Acetylsalicylic
      acid). All participants will also receive the oral immunosuppression medications consisting
      of mycophenolate mofetil or sirolimus and tacrolimus or cyclosporine throughout the study. In
      addition, they will receive intravenous thymoglobulin on days -2, -1, day 0 (transplant), +1,
      and +2 for the first transplant or intravenous basiliximab at the time of transplant and on
      Day 4 for the second and third transplant. Enbrel® (Etanercept) will be given to all
      participants for anti-inflammatory therapy. Islet infusions will occur at the hospital and
      will be given intravenously. Participants will be eligible to receive second and third islet
      infusions if previous infusions fail and they continue to meet the eligibility criteria.
      After each infusion, study visits will occur on Days 1, 3, 7, 14, 21, 28, and 75 and Months 6
      and 12. At these visits, physical exams and blood collection will occur. At some visits,
      urine collection will also occur.
    

Intervention name(s): Low Molecular Weight Sulfated Dextran (LMW-SD); Heparin; CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus); Prograf® (Tacrolimus) OR Cyclosporine; Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant; Simulect® (Basiliximab) - at 2nd or 3rd transplant; Klexane® (Enoxaparinsodium); Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA); Enbrel® (Etanercept)
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Inhibitor of IBMIR; Anticoagulation; Cell proliferation inhibitor; Calcineurin inhibitor; Monoclonal IL-2 receptor blocker; Anticoagulation Prophylaxis; Anticoagulation Prophylaxis; Anti-Inflammatory Therapy
Intervention MeSH terms: Cyclosporine; Sirolimus; Mycophenolic Acid; Etanercept; Heparin; Dextrans; Tacrolimus; Cyclosporins; Thymoglobulin; Antilymphocyte Serum; Basiliximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Insulin dependence