Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake
- Conditions
- OvereatingGlucocorticoidsOverweight and Obesity
- Interventions
- Drug: Placebo
- Registration Number
- NCT06556277
- Lead Sponsor
- Eleonora Seelig
- Brief Summary
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.
- Detailed Description
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)
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 23
- Males aged 18 to 50 years
- BMI≥ 25 kg/m² with a stable weight within past three months before study initiation
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Metyrapone And Hydrocortisone 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). Placebo 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.
- Primary Outcome Measures
Name Time Method Total body fat Two 7-day intervention periods Change in total body fat assessed with a Dual-Energy-X-Ray-Absorptiometry (DXA)
- Secondary Outcome Measures
Name Time Method Total lean mass Two 7-day intervention periods Change in total lean mass assessed with DXA
Insulin Two 7-day intervention periods Change in Insulin assessed with a mixed meal tolerance test
Energy expenditure Two 7-day intervention periods Basal metabolic rate measured with indirect calorimetryy
Immune cells (peripheral blood mononuclear cells) Two 7-day intervention periods Blood sample
Satiation Two 7-day intervention periods Amount of food intake with ad libitum buffet
IL-6 (Inflammatory markers) Two 7-day intervention periods Blood sample
Insulin sensitivity Two 7-day intervention periods Change in insulin sensitivity assessed with a mixed meal tolerance test
Systolic and diastolic blood pressure Two 7-day intervention periods Assessment of blood pressure with a standard blood pressure monitor.
GLP-1 Two 7-day intervention periods Blood sample
Glucagon Two 7-day intervention periods Blood sample
Glucose Two 7-day intervention periods Change in Glucose assessed with a mixed meal tolerance test
C-peptide Two 7-day intervention periods Change in C-peptide assessed with a mixed meal tolerance test
Substrate utilization Two 7-day intervention periods Respiratory quotient assessed with indirect calorimetry
Weight Two 7-day intervention periods Measurement of weight with a standard scale
Motivation Two 7-day intervention periods Motivation to eat measured with a speed clicking test
IL-1RA (Inflammatory markers) Two 7-day intervention periods Blood sample
CRP (Inflammatory markers) Two 7-day intervention periods Blood sample
Thyroid hormones Two 7-day intervention periods Blood sample
Leptin Two 7-day intervention periods Blood sample
IGF1 Two 7-day intervention periods Blood sample
Lipids (mmol/l) ((total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides) Two 7-day intervention periods Blood sample
Satiety Two 7-day intervention periods Appetite rating with visual analogue scale (VAS) from 0mm-100mm (0mm=not at all and 100mm=extreme)
IL-8 (Inflammatory markers) Two 7-day intervention periods Blood sample
Growth hormone Two 7-day intervention periods Blood sample
Ghrelin Two 7-day intervention periods Blood sample
GDF15 Two 7-day intervention periods Blood sample
PYY Two 7-day intervention periods Blood sample
Renin Two 7-day intervention periods Blood sample
ACTH Two 7-day intervention periods Blood sample
Progesterone Two 7-day intervention periods Blood sample
17-hydroxyprogesterone Two 7-day intervention periods Blood sample
11-deoxycorticosterone Two 7-day intervention periods Blood sample
Corticosterone Two 7-day intervention periods Blood sample
18-hydroxycorticosterone Two 7-day intervention periods Blood sample
17-hydroxypregnenolone Two 7-day intervention periods Blood sample
11-deoxycortisol Two 7-day intervention periods Blood sample
Oxytocin Two 7-day intervention periods Blood sample
Catecholamines Two 7-day intervention periods Blood sample
GIP Two 7-day intervention periods Blood sample
CCK Two 7-day intervention periods Blood sample
FGF21 Two 7-day intervention periods Blood sample
Cortisol Two 7-day intervention periods Blood sample
Aldosterone Two 7-day intervention periods Blood sample
Pregnenolone Two 7-day intervention periods Blood sample
Trial Locations
- Locations (1)
University Hospital Basel
🇨🇭Basel, Basel-Stadt, Switzerland