Cardiovascular and Metabolic Physiological Adaptations to Intermittent Hypoxia. Physiological Aspects and Expression of Receptors and Cellular Mediators
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Change in sympathetic activity
研究概览
简要总结
The purpose of this study is to compare cardiovascular physiological adaptation to intermittent hypoxia (IH) of nonobese healthy subjects. The exposure will be two periods of two weeks (IH versus exposure "placebo hypoxia"). The investigators will use pharmacological tools, peripheral vasodilator (amlodipine) or specific blocker of angiotensin receptor (valsartan) versus the taking of a placebo. The allocation of the tool and the exhibition will be randomized (HI / placebo, valsartan / amlodipine). The outcome measures evaluated concern the cardiovascular system, systemic inflammation and tissular and glucose metabolism.
The investigators assume an increase in arterial resistance during the intermittent hypoxia compared to the control group, these being dependent on sympathetic tone.
The investigators hypothesize that the metabolic alterations that will be observed after experimental simulation (IH and fragmentation of sleep for 15 consecutive nights) will be less severe in the valsartan group than in the amlodipine group in comparison with the placebo group.
A serum bank and a gene bank will be performed for the requirements of subsequent studies if necessary.
详细描述
There are many physiological situations in which the organism is exposed to hypoxia, such as exercise and altitude. In addition some pathological situations also involve hypoxia, such as obesity, heart failure, respiratory failure and sleep apnea syndrome.
Hypoxia associated with altitude is frequently marked by the presence of sleep during periodic breathing induces a particular pattern of hypoxia called intermittent hypoxia. Also some subjects are "intolerant altitude" and develop specific pathologies at high altitude (acute mountain evil, pulmonary edema ...).
We recently demonstrated that subjects tolerate the altitude had just intermittent hypoxia while they were sleeping during the simulated altitude. The protective role of intermittent hypoxia in the mechanisms of occurrence of intolerance to altitude remains to be understood more precisely. In fact those who were intolerant to altitude has no periodic breathing and therefore intermittent hypoxia during the oxygen-deficient atmosphere.
Conversely, the sleep apnea syndrome (SAS) also characterized by a HI. It is produced by repeated episodes of airway obstruction during sleep, producing a sequence: respiratory effort, hypoxia / re-oxygenation and sleep interruption.
The HI is associated with both a well established cardiovascular morbidity but also to cardioprotection. This relates to cardiovascular morbidity rise in blood pressure can certainly promote the development after many years of hypertension. On the other hand the presence of sleep apnea syndrome is advanced as a factor favoring the coronary collateral circulation and therefore will bring a cardioprotective effect for patients.
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
- 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
- 是
入选标准
- •Healthy subject
- •Subject aged of 18 years-old at least
- •Diagnostic AHI<15/h and <5% of total sleep time spent with a SaO2<90%
- •Free and informed consent signed
- •Subject covered by social security
- •Negative pregnancy test
排除标准
- •Subject with a medical pathology (respiratory, cardiovascular, renal, metabolic, neurological...)
- •Tobacco consumption > 5 cigarettes/days
- •Alcohol consumption > 3 units/days (1 unit=1 drink)
- •Subject under trusteeship or guardianship
- •Subject unaffiliated with the social security
- •Person deprived of their liberty, adult protected by laws, person hospitalized
- •Ongoing participation in another clinical research study
- •Subject non-cooperative or respectful of obligations inherent in the participation in the study
研究组 & 干预措施
Arm 1: Real hypoxia and ¨Placebo
This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the placebo during the first two weeks and, after the wash-out, receive the treatment of the arm 2.
干预措施: Placebo (Drug)
Arm 2: Hypoxia placebo and Placebo
This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the hypoxia placebo and the placebo during the first two weeks and, after the wash-out, receive the treatment of the arm 1.
干预措施: Placebo (Drug)
Arm 3: Hypoxia and Valsartan
This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the Valsartan during the first two weeks and, after the wash-out, receive the treatment of the arm 4.
干预措施: Valsartan (Drug)
Arm 4: Hypoxia and Amlodipine
This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the amlodipine during the first two weeks and, after the wash-out, receive the treatment of the arm 3.
干预措施: Amlodipine (Drug)
结局指标
主要结局
Change in sympathetic activity
时间窗: Day 1 and at Day 14
The sympathetic activity will be directly measured by microneurography of the peroneal nerve
次要结局
- Measure of metabolic aspects of the OGTT test.(Day 14)
- Measure of adrenergic, inflammatory and metabolic markers in adipose tissues by chronic intermittent hypoxia versus placebo in healthy nonobese subjects.(Day 14)
- Measure variations in parameters of inflammation in adipose tissue by chronic intermittent hypoxia versus placebo in healthy nonobese subjects.(Day 14)
- Assessing markers implicated in the pathophysiology of chronic metabolic diseases after HI versus placebo in healthy nonobese subjects during OGTT.(Day 14)
- Measure the activation of systemic inflammation by chronic HI versus placebo in healthy nonobese subjects. The systemic inflammation will be assessed in non-stress and during the OGTT.(Day 14)
- Change in vascular responsivness(At day 1 and Day 14)
- Change in Sympathetic and vascular determinant of Blood pressure(Day 1 and Day 14)