Einfluss Selektiver I(f)-Blockade Auf Orthostase-Toleranz Und Sympathikusaktivität Bei Gesunden
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Sub-study 'Orthostatic tolerance': Change in heart rate after 20 mins of passive orthostasis. Sub-study 'Sympathetic system': arterial pressure related heart rate
研究概览
简要总结
The study compares three treatment modalities in a human model of Postural orthostatic tachycardia syndrome (POTS): beta-blockers, I(f)-blockers, and placebo.
详细描述
Elevated heart rate may lead to cardiac disease in the long-term. Therefore, drugs lowering heart rate are useful. Beta-blockers are an established treatment modality. They not only lower heart rate but also contractility, which might be undesirable in certain tachycardic disorders.
Postural orthostatic tachycardia syndrome (POTS) patients complain about dizziness, weakness, headache, lightheadedness, fatigue, nausea, and presyncope. In some patients there is elevated heart rate even during supine rest. In POTS patients it is preferable to lower heart rate without reducing cardiac contractility which can be achieved by using so-called I(f)-blockers. Thus, they might be superior to beta-blockers in POTS.
In our study, we artificially generate POTS in healthy male subjects for about 48 hours. We want to compare the cardiovascular effects and orthostatic tolerance of the following treatments: beta-blocker, I(f)-blocker, and placebo.
Moreover, we will quantify changes in cardiovascular autonomic regulation brought about by I(f)-blockade versus placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •healthy male
- •age 18-40 years
- •BMI: 18-30 kg/m²
- •arterial blood pressure <=160/100 mm Hg
- •co-operativity
- •voluntariness
排除标准
- •conditions in which treatment might be ineffective or insecure
- •co-medication within the last 4 weeks
- •participation in another clinical trial within the last 4 weeks
- •unability to understand the study's aim
- •drug or alcohol abuse
- •secondary hypertension
- •creatinine > 130 μM (1.47 mg/dl)
- •GOT/GPT > 2 times normal
- •GGT > 3 times normal
- •contraindications against reboxetine, beta-blocker, ivabradine
- •asthma, psoriasis
- •heart failure (NYHA III or IV)
- •coronary artery disease
- •peripheral occlusive disease
- •cerebrovascular disease
- •ventricular extrasystoles (Lown III-V)
- •atrial fibrillation
- •resting heart rate <60/min
- •neurologic/psychiatric disorder
- •pulmonary hypertension
- •dysthyroid metabolism
研究组 & 干预措施
1
beta-blocker
干预措施: beta-blocker (Metoprolol) (Drug)
2
I(f)-blocker
干预措施: I(f)-blocker (ivabradine) (Drug)
3
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Sub-study 'Orthostatic tolerance': Change in heart rate after 20 mins of passive orthostasis. Sub-study 'Sympathetic system': arterial pressure related heart rate
时间窗: 12-18 hours
次要结局
- 'Orthostatic tolerance': Hemodynamics during head-up tilt. Time to presyncope.(12-18 hours)
- 'Sympathetic system': Muscle sympathetic nerve activity (MSNA).(12-18 hours)