Steroid-free and Long-term Calcineurin-free Trial in Islet Cell Transplantation
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 1
Intervention: Islet transplantation
Intervention description: Islet transplantation
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Islet Transplantation

Summary:

      The purposes of this study are:

        1. To reverse hyperglycemia and insulin dependency in patients with type 1 diabetes
           mellitus through islet transplantation utilizing steroid free, calcineurin-inhibitor
           free immunosuppression.

        2. To assess the long-term function of successful islet transplants in patients with type 1
           diabetes mellitus utilizing islets that have undergone a period of culture.

        3. To determine whether the natural history of the microvascular, macrovascular, and
           neuropathic complications are altered following the successful transplantation of
           islets.
    

Eligibility criteria:

        Inclusion Criteria:

        Potential candidates must have type 1 diabetes mellitus and fulfill one or more of the
        following:

          1. Manifest signs and symptoms that are severe enough to be incapacitating.
             Incapacitating signs and symptoms include hypoglycemic episodes requiring assistance
             by others and hypoglycemia unawareness (the inability to recognize low blood glucoses;
             glucoses < 54 mg/dl). These patients are at high risk for involvement in accidents
             (they can lose consciousness or act irrationally), thus causing harm to themselves
             and/or others.

          2. Patients with poor diabetes control (HbA1c > 8.0% but < 12%), despite intensive
             insulin therapy, as defined by: self monitoring of blood glucose ≥ 4 times/day,
             multiple insulin injections (≥ 3/day) or insulin pump, and close monitoring of blood
             glucose control by an endocrinologist. These patients can experience acute, rapid
             hyperglycemia secondary to several stress factors, that can lead to dehydration,
             disorientation, and in some instances, ketoacidosis.

          3. Progressive diabetic complications. These patients with chronically poor glycemic
             control are at higher risk for the development of a wide variety of complications
             (retinopathy, neuropathy, nephropathy, and cardiovascular disease) associated with
             diabetes.

        Exclusion Criteria:

        Potential candidates will be excluded as per the following criteria:

          1. Age < 18 or > 65 years

          2. Duration of diabetes < 5 years

          3. Do not have a physician that is monitoring diabetes for > 6 months

          4. Body mass index > 26

          5. Weight > 80 kg

          6. Insulin requirement > 1.0 u/kg/d

          7. HbA1c > 12%

          8. Stimulated or basal C-peptide > 0.3 ng/ml

          9. Corrected creatinine clearance < 60 ml/min

         10. Serum creatinine consistently above 1.6 mg/dl

         11. Macroalbuminuria (> 300 mg/24 hours)

         12. Anemia (hemoglobin < 12.0 g/dl for males; < 11 g/dl for females)

         13. Hyperlipidemia (fasting low-density lipoprotein [LDL] cholesterol > 130 mg/dl and/or
             fasting triglycerides > 200 mg/dl)

         14. Abnormal liver function tests (consistently > 1.5 x normal range)

         15. Serological evidence of HIV, HBsAg and/or HBcAb, HBsAb without history of vaccination,
             human t cell lymphotropic virus 1 (HTLV-1), or hepatitis C virus (HCV)

         16. Negative serology for Epstein-Barr virus (EBV) or evidence of acute or chronic
             infection (IgM ≥ IgG)

         17. Lack of updated immunizations per current Centers for Disease Control (CDC) guidelines
             (including lack of immunization against hepatitis B, pneumococcus and influenza -
             during season)

         18. Presence of panel reactive antibodies > 20%

         19. Prostate-specific antigen (PSA) > 4 ng/ml unless malignancy is ruled out

         20. Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis
             can be provided)

         21. X-ray evidence of pulmonary infection or other significant pathology

         22. Gall stones and/or portal hypertension and/or hemangioma on liver ultrasound

         23. Abnormal abdominal or pelvic ultrasound (evidence of masses that are considered
             suspicious for malignancy or adenopathy)

         24. Active peptic ulcer disease

         25. Active infections

         26. Unstable cardiovascular status (including positive stress echocardiography if age >
             35)

         27. Untreated or unstable proliferative diabetic retinopathy

         28. Previous/concurrent organ transplantation (except for failed islet cell or pancreas
             transplantation)

         29. Malignancy or previous malignancy

         30. Any medical condition requiring chronic use of steroids

         31. Active alcohol or substance abuse; smoking in the last 6 months.

         32. Sexually active females who are not:

               -  post-menopausal,

               -  surgically sterile, or

               -  not using an acceptable method of contraception (oral contraceptives, Norplant,
                  Depo-Provera, and barrier devices with spermicide are acceptable; condoms used
                  alone are not acceptable)

         33. Positive pregnancy test or intent for future pregnancy, or male subject's intent to
             procreate

         34. Any condition or any circumstances that make it unsafe to undergo an islet cell
             transplant

         35. Psychogenically unable to comply

         36. Failed psychological evaluation

         37. Persistent leukopenia (white blood cell count < 3,000/uL on more than 3 occasions)