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Sponsored by: |
Mario Negri Institute for Pharmacological Research |
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Information provided by: | Mario Negri Institute for Pharmacological Research |
ClinicalTrials.gov Identifier: | NCT00157586 |
Diabetes mellitus is one of the most common diseases globally, and is considered epidemic in many developed and newly industrialized nations. Diabetes mellitus represents the single largest cause of end-stage renal disease in the U.S. and Europe. At the same time, the primary cause of early death in diabetic patients are cardiovascular complications. Experimental and clinical studies found that angiotensin converting enzyme inhibitors (ACEi) and calcium channel blockers (CCBs) have a specific renoprotective effect and that this effect can be magnified when the two drugs are used in combination. To formally test this hypothesis we designed the Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND) study, a prospective, randomized, double blind trial aimed to compare the effect of 3 years treatment with the ACEi Delapril (30 mg/day), alone or combined to the CCB Manidipine (10 mg/day), versus conventional (non ACEi, non CCB) therapy on the rate of renal function loss and on the incidence of major cardiovascular events in 342 normo- and micro-albuminuric hypertensive type 2 diabetic patients.
Condition | Intervention | Phase |
---|---|---|
Type 2 Diabetes |
Drug: Delapril, Delapril-Manidipine Fixed combination |
Phase III |
Study Type: | Interventional |
Study Design: | Diagnostic, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study |
Official Title: | A Multicenter, Randomized, Prospective, Double-Blind Study to Evaluate the Nephroprotective Effect of Delapril Alone or Combined With Manidipine in Patients With Type 2 Diabetes |
Estimated Enrollment: | 342 |
Study Start Date: | February 2002 |
Estimated Study Completion Date: | June 2008 |
INTRODUCTION Optimal blood pressure, glycemic and lipid control are of utmost importance to minimize the incidence and the progression of chronic renal and cardiovascular complications in patients with diabetes mellitus type 2. Whether angiotensin converting enzyme (ACE) inhibitors alone or combined to calcium channel blockers (CCB) may further reduce the incidence and progression of chronic complications is worth investigating.
AIMS The primary aim of this study is to assess whether at comparable levels of optimal blood pressure and metabolic control, the ACE inhibitor delapril alone or in combination with the dihydropyridine CCB manidipine slow the rate of glomerular filtration rate (GFR) decline as compared with placebo plus conventional antihypertensive therapy in patients with diabetes mellitus type 2 and hypertension. The secondary aim of this study is to assess the effects of delapril and manidipine on the incidence of major cardiovascular events (acute myocardial infarction, ictus or stroke, heart failure requiring hospitalization, revascularization, amputation and cardiovascular mortality).
STUDY POPULATION 342 hypertensive type 2 diabetes patients with normo- or micro-albuminuria. STUDY DESIGN This is a multicenter, prospective, randomized, double-blind, placebo-controlled study. After a 12-week baseline period in which prohibited antihypertensive treatments (ACE inhibitors, angiotensin II receptor antagonists or dihydropyridine calcium channel blockers) will be discontinued, patients will be stratified according to their urinary albumin excretion rate in normo- and micro-albuminuric and then randomized to delapril alone (30 mg/day), delapril (30 mg/day) combined with manidipine (10 mg/day) or placebo given once daily in the morning for at least three years. During the study, systolic and diastolic blood pressure in all treatments groups will be maintained ≤ 120 and 80 mmHg respectively, with fixed doses of study treatments and flexible doses of permitted antihypertensive therapy (diuretics, beta blockers, alfa blockers, centrally acting adrenergic blockers. Blood pressure, blood glucose concentrations and urinary albumin excretion rate will be monitored every three months. Serum lipid concentrations and GFR (estimated with the iohexol plasma clearance) will be measured every six months.
Primary and Secondary Variables. The primary efficacy variable of this study is the rate of GFR decline. The secondary efficacy variable will be the incidence of major cardiovascular events (acute myocardial infarction, ictus or stroke, heart failure requiring hospitalization, revascularization, amputation and cardiovascular mortality).
Ages Eligible for Study: | 40 Years to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Italy | |
Hospital "Ospedali Riuniti di Bergamo" - Diabetologic Unit | |
Bergamo, Italy, 24128 | |
Italy, Bergamo | |
Hospital " Treviglio Caravaggio" - Diabetologic Unit | |
Treviglio, Bergamo, Italy, 24128 | |
Hospital " Bolognini " - Medicine Unit | |
Seriate, Bergamo, Italy, 24068 | |
Hospital of Romano di Lombardia - Diabetologic Unit | |
Romano di Lombardia, Bergamo, Italy, 24058 | |
ASL of Ponte San Pietro - Diabetologic Unit | |
Ponte San Pietro, Bergamo, Italy, 24036 | |
Clinical Research Center for Rare Diseases | |
Ranica, Bergamo, Italy, 24020 | |
Italy, Milano | |
Humanitas Institute - Endocrinology and Diabetologic Unit | |
Rozzano, Milano, Italy, 20089 | |
Slovenia | |
Department of Endocrinolgy, Diabetes and Metabolic Disease - University Medical Center | |
Lubiana, Slovenia |
Principal Investigator: | Piero Ruggenenti, MD | Mario Negri Institute |
Study ID Numbers: | DM/PR/7401/005/00 |
Study First Received: | September 8, 2005 |
Last Updated: | March 14, 2006 |
ClinicalTrials.gov Identifier: | NCT00157586 |
Health Authority: | Italy: Ministry of Health |
Calcium, Dietary Metabolic Diseases Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases |
Delapril Endocrinopathy Metabolic disorder Glucose Metabolism Disorders Manidipine |
Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Therapeutic Uses Calcium Channel Blockers Angiotensin-Converting Enzyme Inhibitors |
Enzyme Inhibitors Cardiovascular Agents Antihypertensive Agents Pharmacologic Actions Protease Inhibitors |