Treatment of Vascular Stiffness in Patients With Autosomal Dominant Polycystic Kidney Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Arterial stiffness induced by high salt diet
研究概览
简要总结
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by cystic kidneys and caused by mutations in the polycystic kidney disease and other rare genes. It is associated with salt-sensitive hypertension, which accounts for the majority of morbidity and mortality. About 70% of patients with ADPKD develop hypertension, prior to the onset of kidney function decline. Early onset hypertension, despite its treatment, is independently associated with rapid kidney function decline. The investigators hypothesize that a high-sodium diet in patients with ADPKD is required for the development of vascular stiffness, which precedes hypertension, and that treatment with amiloride reverses this phenomenon.
详细描述
Objective of the study:
The investigators aim to investigate if arterial stiffness is exacerbated due to a high-salt diet in patients with ADPKD. The investigators also aim to explore whether treatment with amiloride prevents the arterial stiffness caused by a high-salt diet.
Study design:
Randomized, double blinded and placebo-controlled clinical trial with open-label treatment with amiloride
Study population:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults with typical ADPKD diagnosed based on Ravine criteria and/or a documented Pkd 1 or 2 mutation
- •Chronic kidney disease epidemiology collaboration equation estimated glomerular filtration rate ≥60 ml/min/1.73m2
- •Ability to provide informed consent
排除标准
- •Uncontrolled hypertension, defined as an office blood pressure of ≥160/ ≥90 mmHg with or without antihypertensive treatment
- •Concomitant use of ≥ 3 antihypertensive medications
- •When antihypertensive treatment is prescribed for any other treatment indication than hypertension (e.g. cardia arrhythmia)
- •Serum potassium levels >5.5 mmol/L (measured within last 6 months)
- •History of liver disease (excluding liver cysts due to ADPKD)
- •History of heart failure (cardiac ejection fraction < 35%) or cardiac arrhythmia
- •History of diabetes mellitus
- •Active infection or antibiotic therapy
- •Immunosuppressive therapy within the last year
- •Concomitant use of drugs that could influence blood pressure and/or disease progression (Tolvaptan/non-steroidal anti-inflammatory drugs (NSAIDs)/chemotherapy), excluding < 3 antihypertensive drugs
- •Actual pregnancy or unwillingness to adhere to reproductive precautions during the duration of the study
研究组 & 干预措施
Low-salt group (group 2)
All participants will be subjected to a low-salt diet (3.5 grams/day) for six weeks.
Group 2 will receive placebo capsules (6 grams/day) for four weeks. In the last two weeks of the trial, all participants will be treated with amiloride tablets (20 mg daily) in open-label setting.
干预措施: Placebo (Dietary Supplement)
Low-salt group (group 2)
All participants will be subjected to a low-salt diet (3.5 grams/day) for six weeks.
Group 2 will receive placebo capsules (6 grams/day) for four weeks. In the last two weeks of the trial, all participants will be treated with amiloride tablets (20 mg daily) in open-label setting.
干预措施: Amiloride Hcl 5mg Tab (Drug)
结局指标
主要结局
Arterial stiffness induced by high salt diet
时间窗: At week 3, week 5
Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), in high-salt group versus low-salt group.
Effect of treatment with amiloride on arterial stiffness in low-salt group
时间窗: At week 5 and at week 7
Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), before versus after amiloride treatment in low-salt group.
Effect of treatment with amiloride on arterial stiffness in high-salt group
时间窗: At week 5 and at week 7
Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), before versus after amiloride treatment in high-salt group.
次要结局
- Skin sodium accumulation(At week 3, week 5 and at week 7)
- Markers of (vascular) inflammation and endothelial dysfunction(At inclusion, week 3, week 5 and at week 7)
- Salt tasting thresholds(At inclusion, week 3, week 5 and at week 7)
- Blood pressure(At week 3, week 5 and at at week 7)
研究者
dr. M. Salih
Principal Investigator
Erasmus Medical Center