Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake: a Double-blind, Randomized, Placebo-controlled, Cross-over Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Total body fat
研究概览
简要总结
The investigator aim to understand whether food-induced glucocorticoids influence fat mass in overweight and obese people.
In a randomized, cross-over study, 23 overweight and obese volunteers will receive a block and replace therapy that mimics physiological glucocorticoid (GC) rhythm (metyrapone plus hydrocortisone) or placebo. Participants will undergo two identical overfeeding periods with each treatment. With the block and replace therapy food-induced GC peak will be suppressed. Metabolic and immunological parameters will be compared to reveal the effects of GCs during excessive overfeeding, particularly to understand changes in body fat.
详细描述
Obesity is one of the most serious health problems of the 21st century, and new therapies are urgently needed.
Glucocorticoids (GCs) increase with acute food intake. Several clinical studies have found that glucocorticoids contribute to common obesity, but the underlying mechanisms remain unknown. Here, the investigator aim to understand whether GCs influence the total body fat in obese and overweight study participants during excessive overfeeding.
In a randomized, cross-over study, 23 overweight and obese individuals will receive a block and replace therapy that mimics physiological GC rhythm (Metyrapone plus hydrocortisone) or placebo. Participants will undergo two identical overfeeding periods with each treatment. With the block and replace therapy, food-induced GC peak will be suppressed. Metabolic, autonomic, and immunological parameters will be compared.
A) Participants will receive hydrocortisone 19.9mg/d day 1 to day 6 and 12mg on day 7 subcutaneously via a pump in a pulsed fashion (eight times/day) and metyrapone per os (starting with a dose of 750mg/d on day 1 to 2500mg on day 3, which will be kept constant until day 6 and then reduced to 750mg on day 7)
B) Participants will receive placebo (0,9% NaCl solution) 19.9mg/d day 1 to day 6 and 12mg on day 7 subcutaneously via a pump in a pulsed fashion (eight times/day) and placebo pills per os (starting with a dose of 750mg/d on day 1 to 2500mg on day 3, which will be kept constant until day 6 and then reduced to 750mg on day 7)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Males aged 18 to 50 years
- •BMI≥ 25 kg/m² with a stable weight within past three months before study initiation
排除标准
- •Any severe acute or chronic disease, including diabetes mellitus type 2
- •Intake of GLP-1 agonists or hormone therapy
- •Hypercortisolism
- •Casual smoking (more than 6 cigarettes per day)
- •Frequent, heavy alcohol consumption (more than 30g/day)
- •Frequent, heavy caffeine consumption (more than 4 caffeinated drinks/day)
- •Regular physical exercise (more than 4hrs per week)
- •Shift work
- •Participation in an investigational drug trial within the past two months
- •Intake of any steroid-containing drugs, including topical steroids and inhalers, within 4 weeks of the study initiation
- •Known allergy to metyrapone
- •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 day 1 to day 6 and 12 mg/d on day 7 subcutaneously via a pump in a pulsed fashion (eight times/day) and metyrapone per os (starting with a dose of 750 mg/d, then the dose will be increased on day 3, where 2500mg/d is achieved and reduced on day 7 to 750mg).
干预措施: Metyrapone And Hydrocortisone (Drug)
Placebo
During the other study period, subjects receive placebo (0,9% NaCl solution) the same dose of placebo instead of hydrocortisone 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 (Drug)
结局指标
主要结局
Total body fat
时间窗: Two 7-day intervention periods
Change in total body fat assessed with a Dual-Energy-X-Ray-Absorptiometry (DXA)
次要结局
- Catecholamines(Two 7-day intervention periods)
- GIP(Two 7-day intervention periods)
- CCK(Two 7-day intervention periods)
- FGF21(Two 7-day intervention periods)
- Cortisol(Two 7-day intervention periods)
- Aldosterone(Two 7-day intervention periods)
- Pregnenolone(Two 7-day intervention periods)
- Total lean mass(Two 7-day intervention periods)
- Insulin(Two 7-day intervention periods)
- Energy expenditure(Two 7-day intervention periods)
- Immune cells (peripheral blood mononuclear cells)(Two 7-day intervention periods)
- Satiation(Two 7-day intervention periods)
- IL-6 (Inflammatory markers)(Two 7-day intervention periods)
- Insulin sensitivity(Two 7-day intervention periods)
- Systolic and diastolic blood pressure(Two 7-day intervention periods)
- GLP-1(Two 7-day intervention periods)
- Glucagon(Two 7-day intervention periods)
- Glucose(Two 7-day intervention periods)
- C-peptide(Two 7-day intervention periods)
- Substrate utilization(Two 7-day intervention periods)
- Weight(Two 7-day intervention periods)
- Motivation(Two 7-day intervention periods)
- IL-1RA (Inflammatory markers)(Two 7-day intervention periods)
- CRP (Inflammatory markers)(Two 7-day intervention periods)
- Thyroid hormones(Two 7-day intervention periods)
- Leptin(Two 7-day intervention periods)
- IGF1(Two 7-day intervention periods)
- Lipids (mmol/l) ((total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides)(Two 7-day intervention periods)
- Satiety(Two 7-day intervention periods)
- IL-8 (Inflammatory markers)(Two 7-day intervention periods)
- Growth hormone(Two 7-day intervention periods)
- Ghrelin(Two 7-day intervention periods)
- GDF15(Two 7-day intervention periods)
- PYY(Two 7-day intervention periods)
- Renin(Two 7-day intervention periods)
- ACTH(Two 7-day intervention periods)
- Progesterone(Two 7-day intervention periods)
- 17-hydroxyprogesterone(Two 7-day intervention periods)
- 11-deoxycorticosterone(Two 7-day intervention periods)
- Corticosterone(Two 7-day intervention periods)
- 18-hydroxycorticosterone(Two 7-day intervention periods)
- 17-hydroxypregnenolone(Two 7-day intervention periods)
- 11-deoxycortisol(Two 7-day intervention periods)
- Oxytocin(Two 7-day intervention periods)
研究者
Eleonora Seelig
Principal Investigator
University Hospital, Basel, Switzerland