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Sponsors and Collaborators: |
University of Minnesota Juvenile Diabetes Research Foundation National Institutes of Health (NIH) Novartis |
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Information provided by: | University of Minnesota |
ClinicalTrials.gov Identifier: | NCT00286624 |
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.
Condition | Intervention | Phase |
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Type 1 Diabetes Mellitus Hypoglycemia |
Biological: Allogeneic Islets of Langerhans Drug: Everolimus Drug: anti-thymocyte globulin Drug: Cyclosporine |
Phase I Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
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 |
Enrollment: | 6 |
Study Start Date: | March 2003 |
Study Completion Date: | August 2006 |
Primary Completion Date: | August 2006 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Allogeneic islet transplantation with anti-thymocyte globulin induction and cyclosporine and RAD maintenance immunosuppression
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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.
Drug: 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.
Drug: 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.
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.
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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.
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Minnesota | |
University of Minnesota | |
Minneapolis, Minnesota, United States, 55455 |
Principal Investigator: | Bernhard J. Hering, M.D. | University of Minnesota |
Responsible Party: | University of Minnesota ( Bernhard J. Hering, M.D. ) |
Study ID Numbers: | 0207M29841 |
Study First Received: | February 2, 2006 |
Last Updated: | May 2, 2008 |
ClinicalTrials.gov Identifier: | NCT00286624 |
Health Authority: | United States: Food and Drug Administration |
Everolimus Metabolic Diseases Autoimmune Diseases Cyclosporine Clotrimazole Miconazole Tioconazole Diabetes Mellitus Benzocaine |
Endocrine System Diseases Hypoglycemia Cyclosporins Antilymphocyte Serum Diabetes Mellitus, Type 1 Endocrinopathy Glucose Metabolism Disorders Metabolic disorder |
Anti-Infective Agents Molecular Mechanisms of Pharmacological Action Immunologic Factors Immune System Diseases Therapeutic Uses Antifungal Agents |
Physiological Effects of Drugs Enzyme Inhibitors Antirheumatic Agents Dermatologic Agents Immunosuppressive Agents Pharmacologic Actions |