The purpose of this study is to determine the effects of pioglitazone, once daily (QD), on low grade inflammation and vascular function in hypertensive patients.
Patients with insulin resistance and an activated inflammation are prone for cardiovascular complications like myocardial infarction or stroke. Pharmacological interventions reducing vascular inflammation are thought to reduce cardiovascular risk in diabetic and in non-diabetic patients. Intervention with ACE inhibitors like ramipril is an established and widely used treatment for patients with high blood pressure, proven to reduce cardiovascular risk. Treatment of non-diabetic patients with pioglitazone has shown to improve the cardiovascular risk profile in non-diabetic patients beyond its effect on blood glucose levels. The purpose of this study is to evaluate effects on low grade inflammation and vascular function of pioglitazone in non-diabetic, hypertensive patients with pre treatment with angiotensin converting enzyme inhibitors (that will be replaced by the study medication at time of randomization).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
172
Pioglitazone 15 mg, tablets, orally, once daily and ramipril placebo-matching tablets, orally, once daily for two weeks; increased to: Pioglitazone 30 mg, tablets, orally, once daily and ramipril placebo-matching tablets, orally, once daily for up to 10 weeks.
Pioglitazone 15 mg, tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to: Pioglitazone 30 mg, tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks.
Pioglitazone placebo-matching tablets, orally, once daily and ramipril 2.5 mg, tablets, orally, once daily for two weeks; increased to: Pioglitazone placebo-matching tablets, orally, once daily and ramipril 5 mg, tablets, orally, once daily for up to 10 weeks.
Unnamed facility
Deggingen, Baden-Wurttemberg, Germany
Unnamed facility
Rottweil, Baden-Wurttemberg, Germany
Unnamed facility
Spaichingen, Baden-Wurttemberg, Germany
Unnamed facility
Change in the high-sensitivity C-reactive Protein value.
Time frame: Week: 12.
Change from Baseline in Glucose tolerance as assessed by an oral glucose tolerance test.
Time frame: Week: 12.
Change from Baseline in Insulin sensitivity according to the Homeostatic Model Assessment - Sensitivity score and Insulin Secretion.
Time frame: Weeks: 6 and 12.
Change from Baseline in Glycosylated Hemoglobin levels.
Time frame: Week: 12.
Change from Baseline in C-Peptide levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Proinsulin intact levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in 24 hours Blood Pressure Profile.
Time frame: Week: 12.
Change from Baseline in high-sensitivity C-reactive Protein levels.
Time frame: Weeks: 6 and 10.
Change from Baseline in Adiponectin levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Monocyte Chemoattractant Protein-1 levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Matrix metalloproteinase-9 levels.
Time frame: Weeks: 6 and 12.
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Weilersbach, Bavaria, Germany
Unnamed facility
Hanover, Lower Saxony, Germany
Unnamed facility
Cologne, North Rhine-Westphalia, Germany
Unnamed facility
Essen, North Rhine-Westphalia, Germany
Unnamed facility
Werne, North Rhine-Westphalia, Germany
Unnamed facility
Mainz, Rhineland-Palatinate, Germany
Unnamed facility
Schauenburg, Rhineland-Palatinate, Germany
...and 3 more locations
Change from Baseline in P-selectin levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Plasminogen Activator Inhibitor-1 levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Relaxin levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Endothelin 1-21 levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Nitrotyrosine levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Asymmetric Dimethylarginine levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Myeloperoxidase levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in levels of Oxidative Stress as assessed by Per-Ox-Assay.
Time frame: Weeks: 6 and 12.
Change from Baseline in Total Cholesterol levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Triglycerides levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in High Density Lipoprotein levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Low Density Lipoprotein levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Oxidized Low Density Lipoprotein levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Soluble Intercellular Adhesion Molecule levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Soluble Vascular Cell Adhesion Molecule levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Osteoprotegrin levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in 11-dihydroxy-thromboxan B2 levels.
Time frame: Weeks: 6 and 12.
Change from Baseline in Placental Growth Factor levels.
Time frame: Weeks: 6 and 12.