A Randomized, Placebo-controlled, Double Blind, 4-period, Cross-over Trial, to Study the Effects of Aliskiren, Hydrochlorothiazide and Moxonidine on Endothelial Dysfunction in Obesity Related Hypertension
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- UMC Utrecht
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Endothelial function assessed by Flow Mediated Dilation (FMD)
研究概览
简要总结
High blood pressure (hypertension) is an important cause of myocardial infarction and stroke. High blood pressure often occurs in people who are overweight. These people frequently also have abnormal fat and sugar metabolism. The combination of these problems is called the 'metabolic syndrome'.
People with hypertension and obesity currently receive the same drug therapy as people with hypertension, but without obesity. Different classes of drugs are thought to be equally effective in lowering blood pressure.
Next to lowering blood pressure, hypertension treatment can have additional effects, like changes in blood vessel function (the ability to dilate and constrict) or changes is the metabolism of sugar and fat. Particularly in patients with the metabolic syndrome, these additional effects are thought to be of great importance, because they can influence the risk for cardiovascular diseases.
The blood pressure lowering mechanism differs between classes of blood pressure lowering medication. The purpose of this study is to compare the effects of three types of blood pressure lowering medication belonging to different classes. The main outcomes of interest will be blood vessel function (the ability to dilate and constrict) and blood pressure. Moreover, the effect of treatment on additional outcomes, like metabolism of sugar and fat, will be studied.
详细描述
Treatment of obesity related hypertension (ORH) is challenging and has become an important global health problem. According to guidelines, most classes of antihypertensives are equally effective for the treatment of hypertension. However, these guidelines are based on evidence from studies in patients with essential hypertension, but without a specific focus on ORH. There is an increasing body of evidence about the complex pathophysiological mechanisms of ORH. Adipose tissue dysfunction is commonly regarded as a common soil that eventually causes up regulation of the sympathetic nervous system (SNS) and the renin-angiotensin-system (RAS). Moreover, development of hypertension is closely related to development of endothelial dysfunction, dyslipidemia and disorders of glucose metabolism. The investigators hypothesize that treatment with antihypertensives that are directed at down regulation of the SNS (moxonidine) and the RAS (aliskiren) will result in more beneficial effects than treatment with a diuretic (hydrochlorothiazide), because the latter reduces blood pressure by inhibition of sodium resorption, without influencing the underlying disease mechanism. The main outcomes of interest are endothelial function and blood pressure, but many secondary outcomes are studied too.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Aliskiren
干预措施: Aliskiren (Drug)
Aliskiren
干预措施: Placebo (for moxonidine and hydrochlorothiazide) (Drug)
Moxonidine
干预措施: Moxonidine (Drug)
Moxonidine
干预措施: Placebo (for aliskiren) (Drug)
Hydrochlorothiazide
干预措施: Hydrochlorothiazide (Drug)
Hydrochlorothiazide
干预措施: Placebo (for aliskiren) (Drug)
Placebo
干预措施: Placebo (for aliskiren) (Drug)
Placebo
干预措施: Placebo (for moxonidine and hydrochlorothiazide) (Drug)
结局指标
主要结局
Endothelial function assessed by Flow Mediated Dilation (FMD)
时间窗: After 8 weeks treatment
次要结局
- Mean 24-hour systolic/diastolic blood pressure Mean day- and night time systolic/diastolic blood pressure(After 8 weeks treatment)
- Central Blood pressure (estimated with pulse wave analysis)(After 8 weeks treatment)
- Renin-Angiotensin System (RAS) hormone concentrations(After 8 weeks treatment)
- Sympathetic nervous system activity, assessed by Muscle Sympathetic Nerve Activity (MSNA) and Heart Rate Variability (HRV)(After 8 weeks treatment)
- Markers of oxidative stress (concentrations of F2-isoprostanes in urine and oxLDL in plasma)(After 8 weeks treatment)
- Markers of inflammation (hs-CRP in plasma)(After 8 weeks treatment)
- Fractional sodium excretion(After 8 weeks treatment)
- Arterial stiffness (assessed by pulse wave velocity and the pulse wave analysis augmentation index)(After 8 weeks treatment)
- Adipose tissue function (serum concentrations of adipokines)(After 8 weeks treatment)
- Lipid metabolism (serum lipid concentrations)(After 8 weeks treatment)
- Insulin sensitivity, expressed by homeostatic model assessment (HOMA)(After 8 weeks treatment)