Anti-Thymocyte Globulin, Cyclosporine, and RAD in Islet Transplantation
Condition: Type 1 Diabetes Mellitus; Hypoglycemia
MeSH terms: Diabetes Mellitus, Type 1; Hypoglycemia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study was designed to test the safety and efficacy of up to 3 pancreatic alloislet
      transplants in type 1 diabetic patients with hypoglycemia unawareness. 6 subjects were
      transplanted under this protocol using anti-thymocyte globulin induction immunosuppression
      and everolimus with cyclosporine maintenance immunosuppression.
    

Detailed description: 
      This is a Phase I/II study designed to assess the safety and efficacy of sequential islet
      allotransplantation for the reestablishment of stable glycemic control in type 1 diabetic
      recipients. A total of 6 patients with type 1 diabetes have received up to three transplants
      of islets from different donor pancreases.

      Potential candidates for islet allotransplantation included patients age 18 and older with
      type 1 diabetes. Induction immunotherapy for the first transplant consisted of anti-thymocyte
      globulin; basiliximab was used for any subsequent transplants. Peritransplant
      anti-inflammatory treatment with etanercept was given for each islet transplant. Maintenance
      immunosuppression is with cyclosporine and RAD. It is felt that those patients in whom
      metabolic lability/instability, reduced awareness of hypoglycemia, poor glycemic control, and
      progressive secondary complications persist despite continued and intensive efforts made in
      close cooperation with their diabetes care team are particularly likely to have a favorable
      benefit/risk ratio.

      Adverse events, irrespective of their presumed relationship to the transplantation of
      allogeneic islets and/or protocol-regulated treatment products (concomitant therapy), are
      being monitored and recorded throughout the first year after the final islet transplant.

      The proportion of single and sequential donor islet allograft recipients with full (insulin
      independence and HbA1c <7%) and partial (insulin dependence, basal or arginine-stimulated
      C-peptide levels of greater or equal to 0.5 ng/mL and HbA1c <7%) islet graft function at one
      year after the final islet transplant will be assessed. The impact of islet transplantation
      on quality of life will also be assessed.

      The predictive value for posttransplant insulin independence of factors such as insulin
      resistance before and at intervals after pancreatectomy, cellular composition of the
      transplant, number of beta cells transplanted; and viability and insulin secretory response
      of isolated islets are being assessed.
    

Intervention name(s): Allogeneic Islets of Langerhans; Everolimus; anti-thymocyte globulin; Cyclosporine
Intervention type(s): Biological; Drug; Drug; Drug
Intervention description(s): Up to 3 intraportal infusions of cadaveric pancreatic islets of Langerhans. First infusion to contain at least 5,000 islet equivalents/kg body weight. Subsequent infusions to contain at least 3,000 islet equivalents/kg body weight.; Loading dose of 3 mg PO on day -2 relative to transplant, followed at least 12 hours later by dose of 1.5 mg PO BID. The daily dose will be adjusted according to the whole blood 12-hr trough to target 3-15 ng/ml for the first 3 months and 3-12 ng/ml thereafter.; A total of 6 mg/kg IV over 12 hours on days -2, -1, 0, +1, and +2. The dose will be 0.5 mg/kg on day -2, 1.0 mg/kg on day -1, and 1.5 mg/kg on days 0, +1, and +2.; Cyclosporine started on day +1 relative to the first islet transplant. Initial dose of 3 mg/kg/day administered in 2 divided doses; then adjusted to maintain target levels of 400 (350-500) ng/mL for the first three months following islet transplant and 300 (200-350) ng/mL thereafter.
Other intervention name(s): Islets; RAD; ATG; Thymogloblin; Neoral
Intervention MeSH terms: Cyclosporine; Everolimus; Cyclosporins; Antilymphocyte Serum
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment