Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals
- Conditions
- Glucocorticoid Effect
- Interventions
- Drug: Placebo 250 mg TabletsDrug: Placebo (0,9% NaCl solution)
- Registration Number
- NCT05167084
- Lead Sponsor
- Eleonora Seelig
- Brief Summary
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 overfeeding periods with each treatment. With the block and replace therapy, food-induced GC peak will be suppressed. Metabolic and autonomic parameters will be compared to reveal, whether GCs mediate the physiological adaptions to excessive food intake.
Understanding acute effects of GCs upon food intake is critical, since repetitive disruptions of GC secretion may become harmful in chronic conditions.
- Detailed Description
Obesity is one of the most serious health problems of the 21st century. To understand how we regulate our body weight is crucial for developing new treatment targets. Even though body mass index of populations is increasing, the body weight of adults is usually kept stable over time. Indeed, acute excessive food intake triggers a set of adaptions in order to prevent weight gain. The signal that triggers these beneficial adaptions is still unknown. Glucocorticoid (GC) secretion increases with acute food intake and many physiological adaptions to overfeeding coincide with classical glucocorticoid actions. The investigators therefore hypothesize that GCs are the signal that prevents weight gain during acute overfeeding.
The objective of this project is to test whether food-induced GCs represent the physiological signal that defends against weight gain.
The primary objective is to investigate whether reduction in insulin sensitivity is abolished with the block and replace therapy.
Secondary objectives are to investigate whether suppression of GC secretion during excessive food intake impairs the activation of sympathetic nervous system, satiety, satiation, energy expenditure, substrate utilization, blood pressure, secretion of neuroendocrine hormones, lipids and immune cells.
This is a double-blind, randomized, placebo-controlled cross-over study. After screening, subjects will be randomized to two crossover 8-day study periods with a washout period of 28 days:
A) Participants will 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 on day 1 to 2500mg/d on day 4, and then will be kept constant until day 8)
B) Participants will receive placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion and placebo pills per os (starting with a dose of 500 mg/d on day 1 to 2500mg/d on day 4, and then will be kept constant until day 8)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 20
- BMI 18.5 - 25 kg/m2
- 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 trail within the past two months
- Intake of any drugs (prescribed, over the counter or recreational) including topical steroids and inhalers, within 48 hours of the study initiation
- Known allergy to metyrapone
- Inability or unwillingness to provide informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Metyrapone And Hydrocortisone Metyrapone 250 mg Oral Tablets 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 2500mg/d is achieved). Metyrapone And Hydrocortisone Hydrocortisone 19,9mg s.c., pulsatile with a flow rate of 10μl/s 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 2500mg/d is achieved). Placebo Placebo (0,9% NaCl solution) 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. Placebo Placebo 250 mg Tablets 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.
- Primary Outcome Measures
Name Time Method Insulin sensitivity Two 8-day intervention periods Change in insulin sensitivity assessed with a mixed meal tolerance test
- Secondary Outcome Measures
Name Time Method GLP-1 (nmol/l) Two 8-day intervention periods Blood sample
PYY (pg/ml) Two 8-day intervention periods Blood Sample
Aldosterone (Adrenal Steroid Hormones) Two 8-day intervention periods Blood Sample
17-Hydroxypregnenolon (Adrenal Steroid Hormones) Two 8-day intervention periods Blood Sample
Substrate utilisation Two 8-day intervention periods Respiratory quotient assessed with indirect calorimetry
Systolic and diastolic blood pressure Two 8-day intervention periods Assessment of blood pressure with a standard blood pressure monitor.
Renin Two 8-day intervention periods Blood Sample
Pregnenolon (Adrenal Steroid Hormones) Two 8-day intervention periods Blood Sample
TSH (mIU/l) Two 8-day intervention periods Blood Sample
Weight Two 8-day intervention periods Measurement of weight with a standard scale
Energy expenditure Two 8-day intervention periods Basal metabolic rate measured with indirect calorimetry
Progesteron (Adrenal Steroid Hormones) Two 8-day intervention periods Blood Sample
11-Deoxycorticosteron (Adrenal Steroid Hormones) Two 8-day intervention periods Blood Sample
T3 (nmol/l) Two 8-day intervention periods Blood Sample
Satiety Two 8-day intervention periods Appetite rating with visual analogue scale (VAS) from 0mm-100mm (0mm=not at all and 100mm=extreme)
Satiation Two 8-day intervention periods Amount of food intake with ad libitum buffet
Cortisol (nmol/l) total and free Two 8-day intervention periods Blood sample
Corticosteron (Adrenal Steroid Hormones) Two 8-day intervention periods Blood Sample
18-Hydroxycorticosteron (Adrenal Steroid Hormones) Two 8-day intervention periods Blood Sample
17-Hydroxyprogesteron (Adrenal Steroid Hormones) Two 8-day intervention periods Blood Sample
11-Deoxycortisol (Adrenal Steroid Hormones) Two 8-day intervention periods Blood Sample
GIP (nmol/l) Two 8-day intervention periods Blood Sample
T4 (nmol/l) Two 8-day intervention periods Blood Sample
Lipids (mmol/l) ((total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides) Two 8-day intervention periods Blood Sample
HGH (mIU/l) Two 8-day intervention periods Blood Sample
GDF-15 (pg/mL) Two 8-day intervention periods Blood Sample
Sympathetic nervous system activity Two 8-day intervention periods Heart rate variability analysis
Trial Locations
- Locations (1)
University Hospital Basel
🇨🇭Basel, Basel-Stadt, Switzerland