Effect of Vasopressin Antagonism on Renal Sodium and Water Handling and Circulation During Inhibition of the Nitric Oxide System in Healthy Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- CH2O
研究概览
简要总结
The purpose of this study is to investigate the effect of tolvaptan on renal water, sodium and potassium excretion, plasma concentration of vasoactive hormones,central blood pressure, pulse wave velocity (PWV) and augmentation index, basal and during inhibition of nitric oxide synthesis in healthy subjects.
详细描述
Tolvaptan is a vasopressin antagonist (V2-antagonist) and is used in treatment of hyponatremia. Animal studies have demonstrated that inhibition of V2 receptors in the renal principal cell increases renal free water clearance and renal sodium excretion.
Treatment with V2-receptor antagonists increases vasopressin concentration in plasma that stimulates V1-receptors in the vascular bed. This may change both central and peripheral hemodynamics and plasma concentration of vasoactive hormones. Changes in hemodynamics and hormone concentration may consequently change renal sodium and water handling.
The nitric oxide system plays a central role in both renal sodium and water handling and regulation of vascular tone and blood pressure.
The effects of tolvaptan the circulation and kidneys is investigated by using measurements of biomarkers specific for the sodium/water balance in the urine and by measurements of vasoactive hormones in the blood after administration of tolvaptan and L-NMMA infusion.
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
Tolvaptan
Oral administration of 15 mg Tolvaptan on each examination day.
干预措施: Tolvaptan (Drug)
Placebo
Oral administration of 15 mg Unikalk tablet on each examination day.
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
- Fractional sodium excretion(5-6 Hours)
- Urine biomarkers(Aquaporins, Epithelial Sodium Channels γ and β, Sodium/Chloride and Sodium/Potassium/Chloride cotransporter)(5-6 Hours)
- Central blood pressure(5-6 Hours)
- Pulse wave velocity(5-6 Hours)
- Augmentation Index(5-6 Hours)
- Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)(5-6 Hours)
研究者
Erling Bjerregaard Pedersen
Professor, MD, Dr.Sci.
Regional Hospital Holstebro