Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Islet Transplantation
Intervention description: Islet Transplantation in subjects with a previous kidney transplant.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Islet Transplantation

Summary:

      The purpose of this study is to reverse hyperglycemia and insulin dependency, by islet cell
      transplantation, in patients with type 1 diabetes mellitus who have a stable kidney
      allograft.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients between 18 and 60 years of age.

          2. Patients with type 1 diabetes mellitus.

          3. Patients with a renal transplant that is more than 6 months old.

          4. Patients with stable renal graft function for the preceding 6 months, i.e. no episodes
             of rejection and changes in serum creatinine no more than 0.5 mg/dl from baseline.

          5. Patients who are taking tacrolimus, sirolimus +/- steroids for maintenance
             immunosuppression for at least 6 months and are tolerating levels satisfactory for
             islet transplantation without severe complications.

          6. Patients with a body mass index (BMI) of less than or equal to 26.

        Exclusion Criteria:

          1. Stimulated or basal C-peptide > 0.3 ng/ml.

          2. Patients with unstable renal function - serum creatinine greater than 0.5 mg/dl above
             baseline.

          3. Patients with proteinuria (albuminuria > 300 mg in 24 hours +/- protein) of new onset
             since kidney transplantation. If proteinuria or albuminuria is thought to originate
             from the native kidney(s) this will not be an exclusion criterion.

          4. Patients with corrected creatinine clearance of less than 40.

          5. Patients weighing more than 80 kg.

          6. Patients with a body mass index (BMI) of greater than 26.

          7. Insulin requirement > 1.0 U/kg/d.

          8. Anemia (hemoglobin: males < 11.0 g/dl; females < 10.0 g/dl).

          9. Abnormal liver function tests (consistently > 1.5 x normal range).

         10. Unstable diabetic retinopathy.

         11. Evidence of acute or chronic active Epstein-Barr virus (EBV) infection (IgM ≥ IgG).
             Patients will be eligible if serological testing becomes consistent with previous
             exposure (i.e. IgG > IgM).

         12. Patients with history of malignancy or current malignancy other than non-melanomatous
             skin cancer, or finding of any lesions or symptoms during screening that are
             suspicious for malignancy, until properly investigated and ruled out.

         13. Patients with elevation of prostate-specific antigen > 4 unless malignancy has been
             excluded.

         14. Patients with unstable cardiovascular status.

         15. Patients with active infections until adequately treated, unless treatment is not
             judged as necessary by the investigators (including, but not limited to, mild skin and
             nail fungal infections).

         16. Patients with serological evidence of infection with HIV, human t cell lymphotropic
             virus 1 (HTLV 1), HTLV 2, or hepatitis B (patients with serology consistent with
             previous vaccination and a history of vaccination are acceptable).

         17. Patients with history and/or serological evidence of hepatitis C (those patients with
             hepatitis C, already transplanted in this protocol will continue in this trial).

         18. Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis
             can be provided).

         19. Patients with active peptic ulcer disease, gallstones, hepatic hemangioma, or portal
             hypertension.

         20. Patients who are pregnant or breastfeeding, or who intend to procreate.

         21. Patients who are sexually active females who are not:

               -  post-menopausal,

               -  surgically sterile, or

               -  using an acceptable method of contraception (oral contraceptives, Norplant,
                  Depo-Provera, and barrier devices combined with spermicidal gel are acceptable;
                  condoms used alone are not acceptable).

         22. Active alcohol or substance abuse; smoking in the last 6 months.

         23. Patients with evidence of sensitization, i.e. panel reactive antibody (PRA) testing
             greater than 20%.

         24. Lack of updated immunizations per current Centers for Disease Control (CDC)
             guidelines, as well as immunization against hepatitis B, pneumococcus, and influenza
             (during season), unless medically contraindicated.

         25. Patients with psychogenic factors, which are judged at psychological evaluation, which
             make it unsafe to undergo islet transplantation, or which preclude therapeutic
             compliance.

         26. Patients with any condition or any circumstance that would make it unsafe to undergo
             an islet transplant.