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Sponsors and Collaborators: |
University of Zurich Steno Diabetes Center |
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Information provided by: | University of Zurich |
ClinicalTrials.gov Identifier: | NCT00303394 |
Aim: To investigate the therapeutic potential of IL-1Ra in type 2 diabetes.
Rationale: Since the major defect leading to a decrease in b-cell mass in type 2 diabetes is increased apoptosis, therapeutic approaches designed to arrest apoptosis could be a significant new development in its management. This approach might actually reverse the disease to a degree rather than just palliate glycemia. Based on current thinking, treatment with IL-1Ra appears as a promising approach. The prospected effect is blocking of the IL-1b-mediated glucotoxicity and thereby to prevent the decline in b-cell mass, together with a rapid restoration of b-cell function. FDA approval for IL-1Ra in the treatment of rheumatoid arthritis occurred based on a favourable tolerability profile.
Condition | Intervention | Phase |
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Type 2 Diabetes |
Drug: IL-1Ra |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Factorial Assignment, Efficacy Study |
Official Title: | Phase 2 Study of IL-1Ra in Patients With Type 2 Diabetes |
Estimated Enrollment: | 72 |
Study Start Date: | April 2004 |
Estimated Study Completion Date: | March 2006 |
Methodology: This will be a two-centre (University Hospital, Zurich, Switzerland and Steno Diabetes Center, Gentofte, Denmark) study. 72 patients will be randomised according to a double-blind, placebo-controlled protocol in which half of the patients are treated with IL-1Ra, the other half with saline. The treatment period will last 13 weeks. This time-period should be sufficient for reversal of functional glucotoxicity and feasible in terms of patient compliance. Whether 13 weeks of treatment will be sufficient to make significant changes in b-cell mass in unpredictable. However, blocking b-cell apoptosis, while new islet formation and b-cell replication are normal, may initiate enlargement of b-cell mass, which may progress beyond the treatment period. Patient evaluation will be performed at start and after 4, 13, 26, 39 and 52 weeks. Following 13 weeks, patients with a fasting plasma glucose levels > 8 mM or with a glycosylated hemoglobin level (HbA1c) > 8% will be treated with insulin. Insulin treatment will not be initiated earlier to avoid interference with possible effects of insulin on primary outcome in the period where the largest effect of IL-1Ra are expected. To assess effects of IL-1Ra on insulin sensitivity, a subset of 40 patients (20 IL-1Ra- and 20 placebo-treated) will undergo an euglycemic-hyperinsulinemic clamp as well as a muscle and fat biopsy at start and after the end of treatment (13 weeks). The Ethics Committee of both centres have already approved the procedure.
Ages Eligible for Study: | 20 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Denmark, Copenhagen | |
Steno Diabetes Center | |
Gentofte, Copenhagen, Denmark, 2280 | |
Switzerland | |
University Hospital of Zurich, Division of Endocrinology and Diabetes | |
Zurich, Switzerland, 8091 |
Study Chair: | Marc Y Donath, MD | University of Zurich |
Study ID Numbers: | EK-1000-ZH |
Study First Received: | March 14, 2006 |
Last Updated: | March 2, 2007 |
ClinicalTrials.gov Identifier: | NCT00303394 |
Health Authority: | Switzerland: Swissmedic |
Type 2 Diabetes, IL-1, inflammation, glucotoxicity, insulin |
Metabolic Diseases Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Interleukin 1 Receptor Antagonist Protein |
Endocrinopathy Metabolic disorder Glucose Metabolism Disorders Insulin Inflammation |
Therapeutic Uses Antirheumatic Agents Pharmacologic Actions |