Pancreatic Islet Cell Transplantation
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to assess a novel approach to immunosuppression in allogenic
      pancreatic islet cell transplant recipients. In addition, the study aims to assess remote
      site islet processing with culture for pancreatic islet cell transplantation in human
      subjects.
    

Detailed description: 
      The purpose of this study is to assess a novel approach to immunosuppression in allogenic
      pancreatic islet cell transplant recipients. In addition, the study aims to assess remote
      site islet processing with culture for pancreatic islet cell transplantation in human
      subjects.

      Detailed Description: Diabetes mellitus (DM) type I is a disease that has significant social
      and economical impact. The prevalence of the disease in the United States is about 120,000 in
      individuals aged 19 or less and 300,000 to 500,000 at all ages and 150 million worldwide.

      So far there are no mechanical devices able to effectively adjust the dose of insulin
      injected according to the serum glucose in patients with DM. This leads to less than perfect
      sugar control, with episodes of hypoglycemia. Successful pancreas transplantation averts the
      need of insulin administration.

      The emerging alternative to whole organ pancreas transplantation is pancreatic islet cell
      transplantation (ICT). The process is based on the enzymatic isolation of the pancreatic
      islets from an organ procured from a cadaver donor. The islets obtained are injected into the
      liver in the recipient via percutaneous catheterization of the portal venous system. This
      procedure allows the selective transplantation of the insulin-producing cell population
      avoiding open surgery as well as the transplantation of the duodenum and the exocrine
      pancreas and their related morbidity.

      The initial efforts with ICT had only modest results. The immunosuppression regimen was
      similar to the one used in solid organ transplantation, based on high dose steroids and
      calcineurin inhibitors - both agents with diabetogenic effects. The results improved markedly
      with the changes in the manipulations of the islets, and the change in immunosuppression thus
      avoiding the higher doses of steroids and using sirolimus, tacrolimus and daclizumab
      initiated by the investigators group at the University of Alberta in Edmonton, Canada. Their
      protocol requires in general two islet cell infusions in order to attain the critical cell
      mass necessary to achieve insulin-independency. The changes in treatment were adopted as the
      Edmonton Protocol, which is used in several transplant centers, worldwide.

      A novel approach to organ preservation uses the two-layer preservation technique. This allows
      for longer travel time for the eventual shipment of the pancreas to an islet cell processing
      facility remotely located from the donor procurement site.

      The isolation of the islets from the donor pancreas will be performed at the Diabetes
      Research Institute in Miami, Florida, according to the standard currently used by that
      institution. The Diabetes Research Institute is a well-established center with a
      state-of-the-art islet cell isolation facility for the purpose of transplantation in humans,
      accredited and monitored by the FDA according to FDA standards.

      The focus of the research in the ICT is centered on the development of a safe and effective
      procedure that will eventually replace surgical pancreas transplantation together with an
      ideal immunosuppressive regimen that provides safe and effective prevention against
      rejection, while minimizing the adverse events associated that negatively impact transplant
      recipient's quality of life.

      This study is being conducted as a validation of the Edmonton protocol for ICT at our
      institution. Our aim is to test the efficacy of the use of the two-layer preservation
      technique for transport of the donor pancreas to the off-site processing facility and the use
      of islet cell culture in the off-site processing facility before the islet isolate is shipped
      to our center.
    

Intervention name(s): Islet cell transplantation
Intervention type(s): Biological
Intervention description(s): Allogenic islet transplantation
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes Mellitus; Hypoglycemia; Hyperglycemia