The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Satiation
研究概览
简要总结
In a randomized, cross-over study, 20 healthy volunteers will receive a block and replace therapy that mimics physiological GC rhythm (metyrapone plus hydrocortisone) or placebo. Participants will undergo two identical fasting periods with each treatment. With the block and replace therapy, fasting-induced GC peak will be suppressed. Metabolic and autonomic parameters will be compared to reveal whether GCs mediate the physiological adaptions to caloric restriction.
Understanding acute effects of GCs upon caloric restriction is critical, since repetitive disruptions of GC secretion may become harmful in chronic conditions.
详细描述
Obesity is one of the major causes of morbidity and mortality worldwide. Achieving long-term weight loss is challenging, as the body counteracts weight loss to preserve energy by increasing appetite and lowering energy expenditure. These physiological defense mechanisms are the main obstacle to successful weight reduction in obese people.
Therefore, identifying the signals that defend body weight during caloric restriction is essential for developing new antiobesity drugs. Corticosteroids mediate the physiological defense to starvation in rodents. Whether cortisol has the same impact on humans is unknown.
Therefore, we investigate whether cortisol regulates the physiological adaptions to caloric restriction in humans.
The general objective of this project is to investigate whether cortisol mediates physiological adaptions to caloric restriction.
The primary objective is to test whether cortisol mediates the increased appetite during caloric restriction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
盲法说明
Placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •BMI 18.5 - 27 kg/m2
- •Weight stability for 6 months prior to the trial (+/- 2kg)
排除标准
- •Previous medical history for any chronic condition in the last three months, active disease or abnormal physical examination as verified by a qualified physician.
- •Casual smoking (>6 cigarettes per day)
- •Frequent, heavy alcohol consumption (>30g/day)
- •Frequent, heavy caffeine consumption (>4 caffeinated drinks/day)
- •Regular physical exercise (>4hrs per week)
- •Shift workers
- •Participation in an investigational drug trial within the past two months
- •Intake of any drugs (prescribed, over the counter or recreational), within 48 hours of the study initiation
- •Intake of any steroids (including topical or inhaler) six month prior to the study
- •Known allergy to metyrapone or hydrocortisone
- •Inability or unwillingness to provide informed consent
研究组 & 干预措施
Metyrapone And Hydrocortisone
During one of the study periods, subjects receive hydrocortisone 19.9 mg/d subcutaneously via a pump in a pulsed fashion (eight times/day) and metyrapone per os (starting with a dose of 500 mg/d, then the dose will be increased the next days until 3000mg/d is achieved).
干预措施: Metyrapone 250 mg Oral Tablets (Drug)
Metyrapone And Hydrocortisone
During one of the study periods, subjects receive hydrocortisone 19.9 mg/d subcutaneously via a pump in a pulsed fashion (eight times/day) and metyrapone per os (starting with a dose of 500 mg/d, then the dose will be increased the next days until 3000mg/d is achieved).
干预措施: Hydrocortisone 19.9mg s.c., pulsatile with a flow rate of 10μl/s (Drug)
Placebo
During the other study period, subjects receive placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion and the same dose of placebo tablets p.o instead of metyrapone
干预措施: Placebo 250 mg Tablets (Drug)
Placebo
During the other study period, subjects receive placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion and the same dose of placebo tablets p.o instead of metyrapone
干预措施: Placebo (0,9% NaCl solution) (Drug)
结局指标
主要结局
Satiation
时间窗: Two 7-day intervention periods
Amount of food intake with ad libitum buffet
次要结局
- Satiety(Two 7-day intervention periods)
- Food preference(Two 7-day intervention periods)
- Energy expenditure(Two 7-day intervention periods)
- Substrate utilization(Two 7-day intervention periods)
- Blood pressure(Two 7-day intervention periods)
- Weight(Two 7-day intervention periods)
- Body composition(Two 7-day intervention periods)
- Neuroendocrine hormones(Two 7-day intervention periods)
- Lipids(Two 7-day intervention periods)
- Glucose(Two 7-day intervention periods)
- Insulin sensitivity(Two 7-day intervention periods)
- Ketone bodies(Two 7-day intervention periods)
- Sympathetic nervous system activity(Two 7-day intervention periods)
- Immune cells(Two 7-day intervention periods)
- Inflammatory markers(Two 7-day intervention periods)
- Motivation to eat(Two 7-day intervention periods)
- Pleasure from eating(Two 7-day intervention periods)
- Measure of behavioural approach and behavioural inhibition system(Two 7-day intervention periods)
- Eating behaviour type(Two 7-day intervention periods)
研究者
Eleonora Seelig
Principal Investigator
University Hospital, Basel, Switzerland