Islet Transplantation for Type 1 Diabetes
Condition: Diabetes Mellitus, Insulin-Dependent
MeSH terms: Diabetes Mellitus, Type 1
Intervention: Islet Transplantation; Sirolimus; Tacrolimus; Daclizumab; Sulfamethoxazole; Ganciclovir; Trimethoprim; Pentamidine
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria

        Patients may be eligible for this study if they:

          -  Have had Type 1 diabetes mellitus for more than 5 years, and are exhibiting 1 of the
             following, despite intensive insulin management efforts: a) hypoglycemic unawareness,
             as defined by inability to sense hypoglycemia until the blood glucose falls to less
             than 54 mg/dL; b) metabolic instability, with 2 or more episodes of severe
             hypoglycemia (defined as an event with symptoms consistent with hypoglycemia in which
             the patient requires the assistance of another person and which is associated with a
             blood glucose below 54 mg/dL) or 2 or more hospital visits for diabetic ketoacidosis
             over the last year; or c) despite efforts at optimal glucose control, progressive
             secondary complications of diabetes as defined by retinopathy, nephropathy, or
             neuropathy.

          -  Are 18 to 65 years of age.

        Exclusion Criteria

        Patients will not be eligible for this study if they:

          -  Have had severe cardiac disease as defined by: a) recent myocardial infarction within
             the past 6 months; b) angiographic evidence of non-correctable coronary artery
             disease; or c) evidence of ischemia on a functional cardiac exam.

          -  Actively abuse alcohol or substances, including cigarette smoking (must not have
             smoked within the last 6 months).

          -  Have psychiatric problems that prevent them from being a suitable candidate for
             transplantation (such as schizophrenia, bipolar disorder, or major depression that is
             not controlled or stable on current medication).

          -  Have a history of not following prescribed regimens.

          -  Have active infection including hepatitis C virus, hepatitis B virus, human
             immunodeficiency virus (HIV), or Tuberculosis (TB) (or under treatment for suspected
             TB).

          -  Have a history of malignancy, except squamous or basal skin cancer.

          -  Weigh more than 70 kilograms or have a Body Mass Index (BMI) greater than 26 kg/m^2 at
             time of screening.

          -  Have a C-peptide value of 0.3 ng/ml or more following a 5.0 gram intravenous arginine
             infusion challenge.

          -  Are unable to provide informed consent.

          -  Have gallstones or hemangioma in liver.

          -  Have untreated proliferative retinopathy.

          -  Are breast-feeding or pregnant, or intend to try and become pregnant (females) or to
             father a child (males), or fail to follow birth control methods.

          -  Have had a previous transplant, or evidence of anti-human leukocyte antigen (HLA)
             antibody.

          -  Have an insulin requirement of more that 0.7 International Units (IU)/kilograms/day.

          -  Have a blood glycosylated hemoglobin (HbA1c) higher than 12 percent.

          -  Are unable to reach the hospital for transplantation within 2 hours of notification.

          -  Have untreated or treated hyperlipidemia.

          -  Have a medical condition requiring chronic use of steroids.

          -  Use coumadin or other anticoagulants (aspirin is allowed).

          -  Have Addison's disease.

          -  Have a negative screen for Epstein-Barr virus (EBV).