Hemodynamic and Biological Effects of 3 Increasing Doses of Fludrocortisone in Healthy Volunteers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Phenylephrine mean blood pressor dose-response relationship.
研究概览
简要总结
Fludrocortisone, in association with hydrocortisone, has demonstrated an improvement in survival in septic shock patients with relative adrenal insufficiency. However, the utility of low doses of steroids and in particular of mineralocorticoids in septic shock is still discussed.
The purpose of the investigators study is to investigate the effects of 3 increasing doses of fludrocortisone (100 μg, 200 μg, 400 μg) in order to determine which dose allows the best pressor response to phenylephrine in healthy volunteers, and simultaneously assess their respective hemodynamic and biological effects.
详细描述
In a previous study (AFLUCO2) in healthy volunteers with saline-induced hypoaldosteronism, the investigators found that single doses of both hydrocortisone and fludrocortisone induced a significant decrease in the pressor response to phenylephrine, probably due to a rapid non-genomic vasodilatory mechanism, and that these effects were additive.
The investigators also showed that, at the doses used in septic shock, hydrocortisone induced more pronounced mineralocorticoid effects than fludrocortisone and also induced systemic hemodynamic effects whereas fludrocortisone did not.
The investigators now want to perform a dose-response study under normal conditions (ie without saline-induced hypoaldosteronism) and after repeated administrations, to determine the optimal dose of fludrocortisone that allows an increase in the pressor response to phenylephrine and to characterize its concomitant hemodynamic and biological effects.
This placebo-controlled, randomized, double-blind, cross-over, 4-periods (fludrocortisone 100 μg/day, 200 μg/day, 400 μg/day, or placebo) study aims to investigate hemodynamic and biological effects of fludrocortisone administered orally during 5 days, in healthy volunteers.
Each period will be separated from the next one by a washout interval of at least 14 days.
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
- 20 Years 至 25 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Men aged 20 to 25 years
- •Body Mass Index between 20 kg/m² and 25 kg/m²
- •Nonsmoker since at least 6 months
- •Normal clinical examination, electrocardiogram and transthoracic echocardiography
- •Normal routine biological parameters
- •Written informed consent
排除标准
- •History of significant allergy
- •Resting heart rate < 50 bpm
- •Subjects with abnormal hepatic or renal function, or cardiovascular, pulmonary, endocrine or psychiatric disease
- •Ongoing medication during the study
- •Alcohol consumption more than 30g/day or drug addiction
- •Exclusion period mentioned on the national registry for clinical trials volunteers.
- •Subject under legal protection
研究组 & 干预措施
Fludrocortisone 100 μg
- 100 μg/day (25 µg four times daily) of fludrocortisone during 5 days
- Investigations the sixth day
干预措施: Fludrocortisone 100 μg (Drug)
Fludrocortisone 200 μg
- 200 μg/day (50 µg four times daily) of fludrocortisone during 5 days
- Investigations the sixth day
干预措施: Fludrocortisone 200 μg (Drug)
Fludrocortisone 400 μg
- 400 μg/day (100 µg four times daily) of fludrocortisone during 5 days
- Investigations the sixth day
干预措施: Fludrocortisone 400 μg (Drug)
Placebo
- Placebo (four times daily) during 5 days
- Investigations the sixth day
干预措施: Placebo (Drug)
结局指标
主要结局
Phenylephrine mean blood pressor dose-response relationship.
时间窗: 1.5 hour after fludrocortisone administration
次要结局
- Cardiac systolic and diastolic function assessed par transthoracic echocardiography during phenylephrine administration(between 1.5 and 2.5 hours after fludrocortisone administration)
- Central aortic hemodynamic parameters(30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration)
- Systemic hemodynamic parameters(30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration)
- Arterial stiffness : carotid-femoral pulse wave velocity(30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration)
- Plasma parameters(30min before and 1h, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration)
- Urinary parameters(30min before and 2h, 4h, 6h after fludrocortisone administration)
- Area under the plasma concentration versus time curve (AUC)(Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration)
- Plasma half-life of fludrocortisone(Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration)
- Total Body Clearance(Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration)
- Apparent volume of distribution(Just before and 5min, 10min, 20min, 30min, 1h, 1h30, 2h, 3h, 4h, 5h, 6h after fludrocortisone administration)