Effect of Coreg CR on BP, Endothelial Function, Exhaled Nitric Oxide, and Nitric Oxide Production and Oxidation
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
1
Coreg Cr will be up-titrated as needed to achieve blood pressure <130/80
干预措施: carvedilol (Drug)
2
Toprol XL will be up-titrated at weekly intervals to achieve a blood pressure <130/80 mm Hg
干预措施: metoprolol extended release (Drug)
结局指标
主要结局
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
时间窗: 12 weeks
次要结局
未报告次要终点