The Effects of Tolvaptan on Renal Handling of Water and Sodium, Vasoactive Hormones and Circulatory System, During Basal Conditions and During Inhibition of the Nitric Oxide System in Healthy Subjects. A Dose-response Study.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- CH2O
研究概览
简要总结
Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water and sodium excretion. Inhibition of V2R increases vasopressin concentration in plasma, which stimulates V1-receptors in the vascular bed and may change both central and brachial hemodynamics and plasma concentration of vasoactive hormones.
The purpose of the study is to measure the effects of tolvaptan on renal handling of water and sodium, systemic hemodynamics and vasoactive hormones at baseline and during nitric oxide (NO)-inhibition with L-NG-monomethyl-arginine (L-NMMA).
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women, age 18-40 years
- •Body Mass Index (BMI) 18,5-30 kg/m2
排除标准
- •Anamnestic or clinical signs of heart, lung, lever, kidney and brain disease
- •Neoplastic disease
- •Drug abuse
- •Alcohol abuse
- •Medical treatment except peroral anticontraceptive
- •Pregnancy
- •Abnormal blood and urine sample
- •Abnormal ECG
- •Blood donation within a month before examination
- •Arterial hypertension (>140 mmHg systolic and/or 90 mmHg diastolic)
研究组 & 干预措施
15 mg tolvaptan
Oral administration of 15 mg tolvaptan on each examination day.
干预措施: 15 mg tolvaptan (Drug)
30 mg tolvaptan
Oral administration of 30 mg tolvaptan on each examination day.
干预措施: 30 mg tolvaptan (Drug)
45 mg tolvaptan
Oral administration of 45 mg tolvaptan on each examination day.
干预措施: 45 mg tolvaptan (Drug)
Placebo
Oral administration of a Unikalk tablet
干预措施: Placebo (Drug)
结局指标
主要结局
CH2O
时间窗: 5-6 Hours
Measurement of H2O clearance at baseline, during and after L-NMMA infusion
次要结局
- Central and brachial blood pressure(5-6 Hours)
- Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)(5-6 Hours)
- Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)(5-6 Hours)
- Fractional sodium excretion(5-6 Hours)
- Augmentation Index(5-6 Hours)
研究者
Erling Bjerregaard Pedersen
Professor, MD, Dr.Sci.
Regional Hospital Holstebro