Pancreatic Islet Cell Transplantation - A Novel Approach to Improve Islet Quality and Engraftment
Condition: Islet Cell Transplantation; 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: 
      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.

      Isolation of the islets from donor pancreata will occur in the Baylor University Medical
      Center Islet Cell Processing Laboratory (ICPL). The islet cell infusion is performed in the
      Interventional Radiology Suite at Baylor University Medical Center or Baylor All Saints
      Medical Center by an interventional radiologist. The procedure takes place in a suite
      designed for invasive procedures using sterile technique with access to general anesthesia if
      necessary. Following the procedure the patient is observed in the Interventional Radiology
      recovery area for as long as necessary as determined by a Physician and then transferred to
      the Transplant Service for an overnight stay. After recovery, the patient is admitted to the
      hospital on the Transplant Service for a 1-2 day observation.

      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.
    

Intervention name(s): Islet cell transplantation
Intervention type(s): Drug
Intervention description(s): The process is based on the enzymatic isolation of the pancreatic islets of Langerhans from an organ procured from a cadaveric donor; the islets obtained are injected into the liver of 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.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes Mellitus; Hypoglycemia; Hyperglycemia; Type 1 Diabetes; Islet cell transplantation