Endothelial FunctionPhase 4NCT00732511
Coreg CR, Blood Vessel Stiffness and Blood Vessel Function
A Phase 4 study testing carvedilol and metoprolol extended release in people with Endothelial Function and Diabetes Mellitus, run by State University of New York - Downstate Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Endothelial Function, Diabetes Mellitus, Hypertension
- What is being tested?
- carvedilol and metoprolol extended release
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2008to Apr 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes mellitus,
- Stable antidiabetic regimen for 3 months
- Hemoglobin A1c <8.6%
- Stable antihypertensive medication regimen for 3 months or more, including either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker
Who cannot join
- Any clinically significant abnormality on history, physical examination, or laboratory testing which could preclude safe completion of the study
- Significant cardiac conditions
- Lung disease
- Cigarette smoking
- Chronic kidney disease (Stage 3 or greater)
- Type 1 diabetes
- Known contraindication to alpha- or beta-blocker therapy
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
SUNY Downstate Medical Center
Brooklyn, New York, 11203
Nathaniel Winer, M.D., 718-270-6320, nathaniel.winer@downstate.edu
Rozina Rana, M.D., 516-279-8092, rrana786@gmail.com
About this study
Official title: 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.
Read the 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.
- Conditions
- Endothelial Function, Diabetes Mellitus, Hypertension
- Being tested
- carvedilol, metoprolol extended release
- Keywords
- Endothelial dysfunction, Blood vessel stiffness, Nitric oxide, Oxidative stress
- Medical subject headings
- Diabetes Mellitus, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carvedilolDrug
Also called Coreg CR
capsules in doses of 20, 40, and 80 mg; once daily; 12 weeks duration
metoprolol extended releaseDrug
Also called Toprol XL
tablets in doses 50, 100, and 200 mg; once daily; 12 weeks duration
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Coreg Cr will be up-titrated as needed to achieve blood pressure <130/80 Receives: Drug: carvedilol |
| 2 | Active comparator | Toprol XL will be up-titrated at weekly intervals to achieve a blood pressure <130/80 mm Hg Receives: Drug: metoprolol extended release |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2008 (estimated)
- Study startApr 2008
- Primary completionDec 2008 (estimated)
- Study completionApr 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endothelial FunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- State University of New York - Downstate Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Nathaniel Winer, M.D., Principal investigator, Stae University of New York Downstate Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00732511
- Sponsor's protocol ID
- Glaxo Smith Kline 111105
- Status last verified
- Feb 2011
- First submitted
- 11 Aug 2008
- Last updated
- 10 Feb 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Coreg CR on BP, Endothelial Function, Exhaled Nitric Oxide, and Nitric Oxide Production and Oxidation
- ClinicalTrials.gov ID
- NCT00732511
- Acronym / sponsor ID
- Glaxo Smith Kline 111105
- Conditions
- Endothelial Function, Diabetes Mellitus, Hypertension
- Keywords
- Endothelial dysfunction, Blood vessel stiffness, Nitric oxide, Oxidative stress
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- State University of New York - Downstate Medical CenterUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Dec 2008 (estimated)
- Study completion
- Apr 2009 (estimated)
- First posted
- 12 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: carvedilolCoreg Cr will be up-titrated as needed to achieve blood pressure <130/80 |
| 2 | Active comparator | Drug: metoprolol extended releaseToprol XL will be up-titrated at weekly intervals to achieve a blood pressure <130/80 mm Hg |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Type 2 diabetes mellitus,
- Stable antidiabetic regimen for 3 months
- Hemoglobin A1c <8.6%
- Stable antihypertensive medication regimen for 3 months or more, including either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker
Key exclusion criteria (7 listed)
- Any clinically significant abnormality on history, physical examination, or laboratory testing which could preclude safe completion of the study
- Significant cardiac conditions
- Lung disease
- Cigarette smoking
- Chronic kidney disease (Stage 3 or greater)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| carvedilolAlso: Coreg CRcapsules in doses of 20, 40, and 80 mg; once daily; 12 weeks duration | Drug | 1 |
| metoprolol extended releaseAlso: Toprol XLtablets in doses 50, 100, and 200 mg; once daily; 12 weeks duration | Drug | 2 |
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
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nathaniel Winer, M.D. principal investigator
Stae University of New York Downstate Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing carvedilol and metoprolol extended release in people with Endothelial Function and Diabetes Mellitus, run by State University of New York - Downstate Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nathaniel Winer, M.D. (718-270-6320, nathaniel.winer@downstate.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2011.