The Effects of Tolvaptan on Renal Handling of Water and Sodium, Vasoactive Hormones and Central Hemodynamics During Baseline Conditions and After Inhibition of the Nitric Oxide System in Patients With Autosomal Dominant Polycystic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- CH2O (Measurement of H2O clearance)
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) in patients with autosomal dominant polycystic kidney disease.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Caucasian men and women
- •Age between 18-65 years
- •ADPKD, diagnosed by genetic testing of PKD1 (>85%) or PKD2 mutations, or by ultrasonography:
- •patients with negative family history for ADKPD and more than 10 cysts in each kidney and no extrarenal or renal findings that suggest causes to cyst formation.
- •patients with positive family history for ADPKD:
- •15-39 yr of age and at least 3 or more unilateral or bilateral.
- •40-59 yr of age and 2 or more cysts in each kidney.
- •60 yr of age and at least 4 cysts in each kidney.
- •Kidney function corresponding to CKD stages 1-3(eGFR> 30 mL/min/1,73 m2),
- •BMI between 18.5 and 35.5 kg/m2.
排除标准
- •Clinical signs of diseases in the heart, lungs, endocrine organs, brain or neoplastic disease,
- •clinically significant abnormalities in blood or urine sample at the inclusion
- •previous cerebrovascular insults,
- •previous clinical evidence for aneurysm
- •Alcohol or drug abuse,
- •pregnancy or breastfeeding,
- •clinically significant changes in the electrocardiogram,
- •medication except antihypertensive agents and oral contraceptives,
- •blood pressure>170/105 mmHg despite treatment with metoprolol and/or amlodipine.
研究组 & 干预措施
60 mg Tolvaptan
Oral administration of 60 mg tolvaptan on each examination day.
干预措施: Tolvaptan (Drug)
Placebo
Oral administration of a Unikalk tablet.
干预措施: Placebo (Drug)
结局指标
主要结局
CH2O (Measurement of H2O clearance)
时间窗: 5-6 Hours
Measurement of H2O clearance at baseline, during and after L-NMMA infusion
次要结局
- Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)(5-6 Hours)
- Central and brachial blood pressure(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)
- Fractional sodium excretion(5-6 Hours)
研究者
Erling Bjerregaard Pedersen
Professor, MD, Dr.Sci.
Regional Hospital Holstebro