Coreg CR, Blood Vessel Stiffness and Blood Vessel Function | RxWiki

Coreg CR, Blood Vessel Stiffness and Blood Vessel Function

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Endothelial Function Diabetes Mellitus Hypertension
Intervention	Drug: carvedilol Drug: metoprolol extended release
Phase	Phase 4
Sponsor	State University of New York - Downstate Medical Center
Responsible Party	State University of New York - Downstate Medical Center
ClinicalTrials.gov Identifier	NCT00732511
First Received	August 11, 2008
Last Updated	February 9, 2011
Last verified	February 2011

Tracking Information[ + expand ][ + ]

First Received Date	August 11, 2008
Last Updated Date	February 9, 2011
Start Date	April 2008
Estimated Primary Completion Date	April 2009
Current Primary Outcome Measures	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 [Time Frame: 12 weeks] [Designated as safety issue: No]
Current Secondary Outcome Measures	Not Provided

Descriptive Information[ + expand ][ + ]

Brief Title	Coreg CR, Blood Vessel Stiffness and Blood Vessel Function
Official Title	Effect of Coreg CR on BP, Endothelial Function, Exhaled Nitric Oxide, and Nitric Oxide Production and Oxidation
Brief Summary	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.
Detailed Description	The following techniques will be used: Endothelial function will be measured non-invasively by flow-mediated changes in pulsatile blood volume in the finger-tips. Vascular compliance (stiffness) will be assessed by tonometry of the radial pulse wave ("augmentation index") and diastolic puse wave analysis. Plasma nitrate/nitrite levels mirror NO production and will be measured spectrophotometrically by the Griess reaction. Plasma nitrotyrosine, an in vivo marker of NO-dependent damage induced by reactive nitrogen intermediates derived from NO, will be measured by ELISA. Exhaled NO may provide an real-time measure of endothelial cell NO production and can be measured by a hand-held device which contains an electrochemical detector sensitive to 5 ppb.
Study Type	Interventional
Study Phase	Phase 4
Study Design	Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label
Condition	Endothelial Function Diabetes Mellitus Hypertension
Intervention	Drug: carvedilol capsules in doses of 20, 40, and 80 mg; once daily; 12 weeks duration Other Names: Coreg CRDrug: metoprolol extended release tablets in doses 50, 100, and 200 mg; once daily; 12 weeks duration Other Names: Toprol XL
Study Arm (s)	Experimental: 1 Coreg Cr will be up-titrated as needed to achieve blood pressure <130/80 Active Comparator: 2 Toprol XL will be up-titrated at weekly intervals to achieve a blood pressure <130/80 mm Hg

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	40
Estimated Completion Date	April 2009
Estimated Primary Completion Date	December 2008
Eligibility Criteria	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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Nathaniel Winer, M.D. 718-270-6320 nathaniel.winer@downstate.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT00732511
Other Study ID Numbers	Glaxo Smith Kline 111105
Has Data Monitoring Committee	No
Information Provided By	State University of New York - Downstate Medical Center
Study Sponsor	State University of New York - Downstate Medical Center
Collaborators	Not Provided
Investigators	Principal Investigator: Nathaniel Winer, M.D. Stae University of New York Downstate Medical Center
Verification Date	February 2011

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