Islet Transplantation for Type 1 Diabetes
Condition: Diabetes Mellitus, Insulin-Dependent
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to test whether the islet cell transplantation procedures and
      results from a previous study in Edmonton, Canada, can be repeated. The study also is
      designed to learn more about diabetes control using islet cell transplantation.

      This is a Phase I/II study (a study that examines effectiveness and looks for side effects).
      The transplanting of islet cells has been studied in Type 1 diabetic patients whose blood
      sugar levels will not stay normal, despite intensive insulin therapy. A recent study
      conducted in Edmonton, Canada, was able to demonstrate that islet transplantation led to
      insulin independence in a majority of the patients treated. This study extends the results
      obtained from the Edmonton study, which used islet transplantation in Type 1 diabetic
      patients with steroid-free immunosuppression.
    

Detailed description: 
      This is a Phase I/II study (a study that examines effectiveness and looks for side effects).
      The transplanting of islet cells has been studied in Type 1 diabetic patients whose blood
      sugar levels will not stay normal, despite intensive insulin therapy. A recent study
      conducted in Edmonton, Canada, was able to demonstrate that islet transplantation led to
      insulin independence in a majority of the patients treated. This study extends the results
      obtained from the Edmonton study, which used islet transplantation in Type 1 diabetic
      patients with steroid-free immunosuppression.

      Eligible patients were randomly selected from the total pool of people who applied through
      the Immune Tolerance Network. Patients will receive at least 10,000 "islet equivalents" per
      kilogram (2.2 pounds) of body weight. This likely will require 2 separate islet infusions
      from 2 separate donors. Immediately before the first transplant, patients will be given
      anti-rejection (immune suppressing) drugs, including tacrolimus and sirolimus (orally) and
      daclizumab (intravenously). The islets will be infused into the liver through a tube placed
      in the portal vein. Heparin (a medication to prevent blood clots) will be administered with
      the islet infusion. A longer-acting form of heparin will also be given by daily injections
      during the next week after each transplant. After surgery, patients will receive insulin
      intravenously for 24 hours. Patients will have an abdominal ultrasound and blood tests to
      determine liver function. If fewer than 10,000 islets were transplanted, patients will
      continue insulin treatment, with the dosages adjusted if necessary to account for the
      transplanted islets. They will take daclizumab every 2 weeks for 8 weeks and tacrolimus and
      sirolimus daily. Patients will be given antibiotics to prevent infections. Blood tests to
      determine how much immunosuppressant drug is in the blood will be performed until the drug is
      at a stable level. Periodically there will be tests to see if the islet cells are
      functioning. Blood will be drawn to check drug levels and for other tests routinely. Daily
      insulin requirements will be checked, and these will be recorded monthly. Patients will be
      followed for at least 1 year post last islet transplantation. Additional follow-up may be
      provided at least annually for up to 9 years post first transplantation.
    

Intervention name(s): Islet Transplantation; Sirolimus; Tacrolimus; Daclizumab; Sulfamethoxazole; Ganciclovir; Trimethoprim; Pentamidine
Intervention type(s): Procedure; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Participants will receive portal vein islet infusions (up to 3), e.g., islet transplantations, with a targeted total of exceeding 10,000 islet equivalents per kilogram of body weight (IE/kg) per infusion. Up to three transplants are possible depending on individual results.; Administered at a dose of 0.2 mg/kg by mouth once pre-transplantation then 0.1 mg/kg daily post-transplantation. Dosing will be adjusted to achieve a trough peripheral blood level of 12-15 ng/mL x3 months after transplantation and 7-12 ng/mL for the remainder of the study.; Administered at a dose of 1 mg by mouth once pre-transplantation followed by 1 mg twice daily post transplantation. Levels will be adjusted to achieve a peripheral blood trough level of 3-6 ng/mL for maintenance immunosuppression.; Administered at a dose of 1 mg/kg intravenously immediately pre-transplantation and 2, 4, 6, and 8 weeks post-transplantation, totaling 5 doses(over 8 weeks). Further daclizumab dosing may be necessary based on individual results and islet transplantation needs.; An antibacterial used to prevent opportunistic infections; An antiviral used to kill viruses and stop viral replication; An antibacterial used to prevent opportunistic infections; An antiprotozoal used to prevent disease
Intervention MeSH terms: Sirolimus; Pentamidine; Trimethoprim; Sulfamethoxazole; Ganciclovir; Ganciclovir triphosphate; Tacrolimus; Daclizumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment