Coreg CR, Blood Vessel Stiffness and Blood Vessel Function

Hypertension Clinical Trial

Official title:

Effect of Coreg CR on BP, Endothelial Function, Exhaled Nitric Oxide, and Nitric Oxide Production and Oxidation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00732511
• Other study ID #: Glaxo Smith Kline 111105
• Status: Recruiting
• Phase: Phase 4
• First received: August 11, 2008
• Last updated: February 9, 2011
• Start date: April 2008
• Est. completion date: April 2009

Study information

• Verified date: February 2011
• Source: State University of New York - Downstate Medical Center
• Contact: Nathaniel Winer, M.D.
• Phone: 718-270-6320
• Email: nathaniel.winer[@]downstate.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Diabetes Mellitus
• Endothelial Function
• Hypertension

Intervention

Drug:
• carvedilol
capsules in doses of 20, 40, and 80 mg; once daily; 12 weeks duration
• metoprolol extended release
tablets in doses 50, 100, and 200 mg; once daily; 12 weeks duration

Locations

Country	Name	City	State
United States	SUNY Downstate Medical Center	Brooklyn	New York

Sponsors (1)

Lead Sponsor	Collaborator
State University of New York - Downstate Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		12 weeks	No