Coreg CR, Blood Vessel Stiffness and Blood Vessel Function

February 9, 2011 updated by: State University of New York - Downstate Medical Center

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Enrollment (Anticipated)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Toprol XL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

State University of New York - Downstate Medical Center

Investigators

  • Principal Investigator: Nathaniel Winer, M.D., Stae University of New York Downstate Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2008

Primary Completion (Anticipated)

December 1, 2008

Study Completion (Anticipated)

April 1, 2009

Study Registration Dates

First Submitted

August 11, 2008

First Submitted That Met QC Criteria

August 11, 2008

First Posted (Estimate)

August 12, 2008

Study Record Updates

Last Update Posted (Estimate)

February 10, 2011

Last Update Submitted That Met QC Criteria

February 9, 2011

Last Verified

February 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Glaxo Smith Kline 111105

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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