Islet Cell Transplantation Alone and CD34+ Donor Bone Marrow Cell Infusion in Type 1 Diabetes Mellitus
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Islet Transplantation and Bone Marrow
Intervention description: Islet transplantation and CD34 Bone Marrow infusion in subjects with type 1 diabetes.
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:

      SPECIFIC AIMS:

        -  To reverse hyperglycemia and insulin dependency in patients with Type 1 diabetes
           mellitus by islet cell transplantation.

        -  To induce a state of donor specific tolerance and eliminate the need for continuous
           immunosuppressive therapy by simultaneous transplantation of donor bone marrow cells
           with islets and utilization of the monoclonal antibody Campath-1H for induction of
           Immunosuppression.

        -  To assess long-term function of successful islet cell transplants in patients with Type
           1 diabetes mellitus.

        -  To determine whether the natural history of the microvascular, macrovascular and
           neuropathic complications are altered following successful transplantation of islet
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients between 18 and 65 years of age

          2. Patients with type 1 diabetes mellitus for more than 5 years duration

          3. One or more of the following:

               -  Hypoglycemia unawareness - judged by history of blood sugars <54 on glucometer
                  without symptoms and/or hypoglycemic episodes requiring assistance from either
                  family, glucagon administration or emergency services

               -  Poor diabetes control (HbA1c>8% or >2 visits/yr to hospital for treatment of
                  ketoacidosis) despite intensive insulin therapy

               -  Progressive complications of type 1 diabetes mellitus

          4. Body Mass Index (BMI) ≤26

        Exclusion Criteria:

          1. Untreated proliferative diabetic retinopathy;

          2. HbA1C > 12%;

          3. Insulin requirement > 1.0u/kg/d

          4. Stimulated or basal C-peptide > 0.3 ng/ml

          5. Creatinine clearance < 60 and/or serum creatinine consistently > 1.5mg/dl;

          6. Macroalbuminuria > 300mg albumin in 24 hours

          7. Presence of panel reactive antibodies > 20%;

          8. Previous/concurrent organ transplantation (except failed islet cell transplantation);

          9. Any medical condition requiring chronic use of steroids;

         10. Malignancy or previous malignancy (except non-melanomatous skin cancer);

         11. X-ray evidence of pulmonary infection;

         12. Active infections;

         13. Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis
             can be provided)

         14. Active peptic ulcer disease,

         15. Gall stones and/or portal hypertension and/or hemangioma on liver ultrasound;

         16. Serological evidence of HIV, HBV (HBsAg+ and/or HBcAb+ and/or HBsAb+ without evidence
             of vaccination), HTLV-1 or HCV;

         17. Negative serology for Epstein Barr virus (EBV) or evidence of acute infection
             (IgM>IgG);

         18. Abnormal liver function test;

         19. Anemia (hemoglobin <12.0 g/dl);

         20. Hyperlipidemia (fasting total cholesterol >240mg/dl and/or fasting triglycerides
             >200mg/dl and/or fasting LDL cholesterol>140mg/dl);

         21. Body Mass Index above 26 and/or weight >80kg;

         22. Prostate specific antigen (PSA) > 4 ng/ml;

         23. Unstable cardiovascular status (including positive stress echocardiography if >age
             35);

         24. Active alcohol or substance abuse;

         25. Sexually active females who are not: a) post-menopausal, b) surgically sterile, or c)
             not using an acceptable method of contraception (oral contraceptives, Norplant,
             Depo-Provera, and barrier devices are acceptable; condoms used alone are not
             acceptable);

         26. Positive pregnancy test or intent for future pregnancy, or male subject's intent to
             procreate.

         27. Any condition or any circumstances that makes it unsafe to undergo an islet cell
             transplant.

         28. History of previous transplant or previous bone marrow infusion.

         29. Persistent leucopenia (white blood cell count <3,000/mm3