Coreg CR, Blood Vessel Stiffness and Blood Vessel Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00732511
Recruitment Status : Unknown
Verified February 2011 by State University of New York - Downstate Medical Center.
Recruitment status was:  Recruiting
First Posted : August 12, 2008
Last Update Posted : February 10, 2011
Information provided by:
State University of New York - Downstate Medical Center

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.

Condition or disease Intervention/treatment Phase
Endothelial Function Diabetes Mellitus Hypertension Drug: carvedilol Drug: metoprolol extended release Phase 4

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  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: Effect of Coreg CR on BP, Endothelial Function, Exhaled Nitric Oxide, and Nitric Oxide Production and Oxidation
Study Start Date : April 2008
Estimated Primary Completion Date : December 2008
Estimated Study Completion Date : April 2009

Arm Intervention/treatment
Experimental: 1
Coreg Cr will be up-titrated as needed to achieve blood pressure <130/80
Drug: carvedilol
capsules in doses of 20, 40, and 80 mg; once daily; 12 weeks duration
Other Name: Coreg CR
Active Comparator: 2
Toprol XL will be up-titrated at weekly intervals to achieve a blood pressure <130/80 mm Hg
Drug: metoprolol extended release
tablets in doses 50, 100, and 200 mg; once daily; 12 weeks duration
Other Name: Toprol XL

Primary Outcome Measures :
  1. 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 ]

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00732511

Contact: Nathaniel Winer, M.D. 718-270-6320
Contact: Rozina Rana, M.D. 516-279-8092

United States, New York
SUNY Downstate Medical Center Recruiting
Brooklyn, New York, United States, 11203
Contact: Nathaniel Winer, M.D.    718-270-6320   
Contact: Rozina Rana, M.D.    516-279-8092   
Sponsors and Collaborators
State University of New York - Downstate Medical Center
Principal Investigator: Nathaniel Winer, M.D. Stae University of New York Downstate Medical Center

Responsible Party: Nathaniel Winer, M.D., Principal Investigator, State University of New York Downstate Medical Center Identifier: NCT00732511     History of Changes
Other Study ID Numbers: Glaxo Smith Kline 111105
First Posted: August 12, 2008    Key Record Dates
Last Update Posted: February 10, 2011
Last Verified: February 2011

Keywords provided by State University of New York - Downstate Medical Center:
Endothelial dysfunction
Blood vessel stiffness
Nitric oxide
Oxidative stress

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Protective Agents
Anti-Arrhythmia Agents
Antihypertensive Agents
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists