Anti-Thymocyte Globulin, Cyclosporine, and RAD in Islet Transplantation (NITA)
|Type 1 Diabetes Mellitus Hypoglycemia||Biological: Allogeneic Islets of Langerhans Drug: Everolimus Drug: anti-thymocyte globulin Drug: Cyclosporine||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A One-Year, Single-Center, Prospective, Open-Label Study of the Safety, Tolerability, and Preliminary Efficacy of Anti-Thymocyte Globulin, Cyclosporine, and RAD in Type 1 Diabetic Islet Transplant Recipients|
- • The incidence, timing, and severity of adverse events during one year after the first and any subsequent islet transplants. [ Time Frame: 1 year ]
- • Incidence and severity of hypoglycemia during the first year after the first and any subsequent islet transplants. [ Time Frame: 1 yr ]
- • The proportion of recipients who develop alloantibodies directed at islet donor alloantigens during the first year after the first and any subsequent islet transplants. [ Time Frame: 1 year ]
- • The proportion of subjects who achieve insulin independence in the first year after single-donor or sequential transplantation. [ Time Frame: 1 year ]
- • The proportion of islet allograft recipients with full and partial islet graft function at one year after the most recent islet transplant. [ Time Frame: 1 year ]
- • Glycemic control and insulin secretory responses during the first year after the first and any subsequent transplants. [ Time Frame: 1 year ]
- • The effect of donor age, pretransplant islet insulin secretory response in vitro, number of transplanted islet equivalents (IEQ), number of transplanted beta cells, pretransplant recipient insulin requirements and action, recipient body mass index (BM [ Time Frame: Day of transplant ]
- • The impact of islet transplantation on the quality of life of transplant recipients. [ Time Frame: 1 year ]
|Study Start Date:||March 2003|
|Study Completion Date:||August 2006|
|Primary Completion Date:||August 2006 (Final data collection date for primary outcome measure)|
Allogeneic islet transplantation with anti-thymocyte globulin induction and cyclosporine and RAD maintenance immunosuppression
Biological: Allogeneic Islets of Langerhans
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.
Other Name: IsletsDrug: Everolimus
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.
Other Name: RADDrug: anti-thymocyte globulin
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.
Other Names:Drug: Cyclosporine
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 Name: Neoral
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00286624
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Bernhard J. Hering, M.D.||University of Minnesota - Clinical and Translational Science Institute|