Pancreatic Islet Cell Transplantation
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1
Intervention: Islet cell transplantation
Intervention description: Allogenic islet transplantation
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus; Hypoglycemia; Hyperglycemia

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient has been fully informed and has signed an Institutional Review Board (IRB)
             approved informed consent form and is willing and able to follow study procedures for
             the full 2 years

          2. Patient is expected to receive an islet cell transplant (up to 3 infusions) for type I
             diabetes mellitus

               -  Type I diabetes of more than 5 years duration

               -  Age between 18 and 65

               -  Unstable diabetes mellitus control, as defined by glucose measurements above 200
                  mg/dL and/or below 80 mg/dL despite adequate medical care

               -  Hypoglycemia unawareness, as defined by episodes of loss of cognitive function

               -  Incapacitating signs and symptoms, as defined by the referring physician

               -  Poor control of HbA1c > 8%

               -  Psychogenically able to comply, in the opinion of the investigator

          3. Female patients of childbearing potential must have a negative urine or serum
             pregnancy test upon hospitalization or within 7 days prior to enrollment and have
             agreed to utilize effective birth control throughout the study as well as for 6 weeks
             following study completion.

        Exclusion Criteria:

        Patients meeting any of the following criteria will be excluded from study participation.

          1. Patient has previously received or is receiving an organ or bone marrow transplant

          2. Patient has a known hypersensitivity to Tacrolimus, sirolimus, daclizumab, or CellCept

          3. Patient is pregnant or lactating

          4. Patient has participated in a blinded trial or participated in a trial involving a
             non-marketed (investigational) drug within 3 months of enrollment

          5. Patient has participated in a trial involving a marketed drug or an infusion device
             within 30 days of the start of the trial

          6. Glomerular filtration rate (GLOFIL) < 60 mL/min

          7. Serum Creatinine > 1.6 mg/dL consistently

          8. Body mass index > 30

          9. Autoimmune thyroiditis

         10. Malignancy other than basal cell carcinoma or squamous cell carcinoma

         11. Radiographic evidence of pulmonary infection

         12. Evidence of liver disease

         13. Portal hypertension

         14. Active infections

         15. Hypercoagulable states (history of recurrent venous thrombosis, defined thrombophilia)

         16. Bleeding / coagulation disorders

         17. Basal insulin C-Peptide > 0.3 ng/dL

         18. Insulin C-peptide > 0.3 ng/dL during stimulation test

         19. HbA1c > 12%

         20. Insulin requirement > 1 IU/kg/day

         21. Seropositivity for Human immunodeficiency virus (HIV), hepatitis B virus (HBV),
             hepatitis C virus (HCV), Human T-cell leukemia virus-1 (HTLV-1)

         22. Abnormal Pap smear in the last two months, active gynecological infection

         23. Positive exercise or chemical tolerance test

         24. Steroid dependence

         25. Substance/alcohol abuse

         26. Untreated proliferating diabetic retinopathy aa) Purified protein derivative (PPD)
             conversion or positive PPD without isonicotinic acid hydrazide (INH) bb) No Primary
             care physician or primary care physician less than 6 months cc) Smoking in the last 6
             months dd) Abnormal Complete Blood Count (CBC) / Hemoglobin < 12 g/dL ee)
             Macroalbuminuria > 300 mg/24 hours ff) History of thyroid disease other than
             autoimmune disease gg) Untreated hyperlipidemia - Total Cholesterol (TC) > 240 mg/dL,
             Triglycerides (TGC) > 200 mg/dL, Low Density Lipoprotein (LDL) > 140 mg/dL hh)
             Untreated hyponatremia, hypokalemia, hypercalcemia, hypocalcemia ii) Iodine contrast
             allergy jj) Prostate Specific Antigen (PSA) > 4 kk) Panel Reactive Antibody (PRA) >
             20% ll) Active peptic ulcer disease/gallstones/hemangioma mm) Abnormal mammogram