Endothelial Function | Coreg CR, Blood Vessel Stiffness and Blood Vessel Function
Endothelial Function research study
What is the primary objective of this study?
We are comparing the blood pressure-lowering effects of two marketed medications, Coreg CR and Toprol XL. Although both drugs reduce blood pressure by blocking the action of noradrenaline on beta-receptors in the blood vessels, Coreg CR also blocks alpha-receptors, which may provide added blood pressure-lowering. In addition, Coreg CR may have anti-oxidant actions. Cells which line blood vessels (termed \"endothelial cells\") make nitric oxide (NO), which relaxes the muscle cells encircling the blood vessels, causing a reduction in blood pressure. When body cells use oxygen, they normally produce \"free radicals\", which can destroy NO,leading to high blood pressure, heart damage and worsenimg of diabetes. Antioxidants remove free radicals and prevent or repair this damage. In this study we will measure endothelial cell function, blood vessel wall stiffness, NO in exhaled breath, and blood levels of substances which reflect NO production and destruction to determine if a pure beta-blocker (Toprol XL) differs from an alpha/beta blocker (Coreg CR) in these effects. We will also examine the mechanism by which such differences might occur.
Who is eligible to participate?
Inclusion Criteria: 1. Type 2 diabetes mellitus, 2. Stable antidiabetic regimen for 3 months 3. Hemoglobin A1c <8.6% 4. Stable antihypertensive medication regimen for 3 months or more, including either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker Exclusion Criteria: 1. Any clinically significant abnormality on history, physical examination, or laboratory testing which could preclude safe completion of the study 2. Significant cardiac conditions 3. Lung disease 4. Cigarette smoking 5. Chronic kidney disease (Stage 3 or greater) 6. Type 1 diabetes 7. Known contraindication to alpha- or beta-blocker therapy
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:carvedilolcapsules in doses of 20, 40, and 80 mg; once daily; 12 weeks duration
Drug:metoprolol extended releasetablets in doses 50, 100, and 200 mg; once daily; 12 weeks duration
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
1Coreg Cr will be up-titrated as needed to achieve blood pressure <130/80
2Toprol XL will be up-titrated at weekly intervals to achieve a blood pressure <130/80 mm Hg
Start Date: April 2008
Completed Date: April 2009
Phase: Phase 4
Primary Outcome: Effect of Coreg CR compared to Toprol XL on endothelial function, vascular compliance, and parameters of oxidative stress from time of randomization to study drug termination
Study sponsors, principal investigator, and references
Principal Investigator: Nathaniel Winer, M.D.
Lead Sponsor: State University of New York - Downstate Medical Center