Evaluation of the Interaction Between a Calcimimetic Agent (Cinacalcet) and the Renin Angiotensine Aldosterone System in Healthy Volunteers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Effect of cinacalcet compared to placebo on plasma renin activity
研究概览
简要总结
The aim of this study is to evaluate, in healthy volunteers, the acute modulating effect of cinacalcet on the RAAS, the effect of furosemide on parathyroid secretion of PTH and the interaction between furosemide and cinacalcet on parathyroid hormone secretion.
详细描述
The clinical trial will be monocentric (Service of Nephrology and Hypertension at CHUV, Lausanne) and will include 24 patients. The volunteers will get involved after inclusion (Inclusion Visit) in a crossover study over two double-blind periods. The order of the two periods (placebo or cinacalcet) will be randomized. Each period comprises 3 days of a low-sodium diet (50 mmol of Na+ per day, equivalent to 3 grams of salt/day), followed by an investigation day at the hospital during which the subjects will be studied before and after exposure to the cinacalcet or placebo. The 2 periods will be separated by a therapeutic wash-out lasting 14-28 days. The total length of the study per participant will be 1, max. 2 months.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy subject
- •Age > 18 and < 45 years old
- •Caucasian
- •Non-smoker
- •BMI >18 and < 25 Kg/m2
- •Normal clinical examination
- •ECG normal, 12 leads
- •Systolic arterial pressure (SBP) ≥100 ≤ 139 mmHg and diastolic arterial pressure (DBP) ≥50 ≤ 89 mmHg (after 5 minutes lying down, 3 measurements at 2-minute intervals; Omron machine; left arm)
- •Heart rate (HR) ≥ 45 ≤ 90 beats/min
- •Subject capable of understanding the written information and the written consent form.
- •Subject must have given written, dated and signed consent before starting any trial procedure.
排除标准
- •Age < 18 or > 45 years old
- •Electrolyte disturbances, defined as any sodium, potassium, total or ionized calcium, phosphate or magnesium value outside of the laboratory's reference values (at the Inclusion Visit).
- •Seropositive for HIV, HBV or HCV (at the Inclusion Visit).
- •Positive detection of drugs in urine (opiates, cannabinoids, cocaine, benzodiazepines, amphetamines or barbiturates) (at the Inclusion Visit).
- •Fall in SBP > or DBP > 10 mmHg after standing for 1 minute or any clinical manifestation of postural hypotension (at the Inclusion Visit).
- •Any history of diseases or clinically significant conditions which may be gastrointestinal (such as gastritis or gastric ulcer), respiratory, psychiatric, neurological (medical history of convulsions), renal, hepatic or cardiac or other diseases/conditions or abnormal physical signs which may interfere with the study's objectives. The investigator may disqualify any subject for a valid medical or psychiatric reason.
- •Ongoing involvement or in the 60 days prior to the Inclusion Visit in another research study.
- •Chronic use of any medication (prescribed or not) during the 4 weeks prior to the Inclusion Visit (only the use of medications such as paracetamol for headaches will be tolerated at the lowest dose possible.
- •Use of any medication known as CYP P450 3A4 inhibitors during the 12 weeks prior to the Inclusion Visit (amiodarone, diltiazem, verapamil, ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole, miconazol, ritonavir, nelfinavir, amprenavir, indinavir, atazanavir, erythromycin, clarithromycin, josamycin, telithromycin)
- •Donation of blood, plasma and/or marrow in the 3 months prior to the Inclusion Visit
- •Medical history of dependence on drugs or alcohol abuse as defined by the DSM IVR, criteria for diagnosing drug and alcohol abuse and dependence on drugs.
- •Medical history of intolerant reactions to cinacalcet or furosemide (or derivatives of sulfamides)
研究组 & 干预措施
calcimimetic agent (cinacalcet)
3 days of a low-sodium diet (50 mmol of Na+ per day, equivalent to 3 grams of salt/day), followed by an investigation day at the hospital during which the subjects will be studied before and after exposure to the cinacalcet or the placebo. The 2 periods will be separated by a therapeutic wash-out lasting 14-28 days. The total length of the study per participant will be 1, max. 2 months
干预措施: Cinacalcet 60 MG (Drug)
Placebo
3 days of a low-sodium diet (50 mmol of Na+ per day, equivalent to 3 grams of salt/day), followed by an investigation day at the hospital during which the subjects will be studied before and after exposure to the cinacalcet or placebo. The 2 periods will be separated by a therapeutic wash-out lasting 14-28 days. The total length of the study per participant will be 1, max. 2 months
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Effect of cinacalcet compared to placebo on plasma renin activity
时间窗: up to 36 days
to determine the acute effect of a single high dose of cinacalcet compared to placebo on plasma renin activity (PRA), under RAAS-stimulating conditions (low sodium diet, furosemide injection) by PRA plasma measure
次要结局
- effect of cinacalcet administered as single dose (compared to placebo) on plasma aldosterone and on hemodynamics(up to 36 days)
研究者
Michel Burnier
Professor
Centre Hospitalier Universitaire Vaudois