Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake (Gluco-Max)

Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake: a Double-blind, Randomized, Placebo-controlled, Cross-over Study

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.

Study Overview

• Status: Completed
• Conditions: Overweight and Obesity; Overeating; Glucocorticoids
• Intervention / Treatment: Drug: Metyrapone And Hydrocortisone; Drug: Placebo

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)

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, 4031
      • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males aged 18 to 50 years
• BMI≥ 25 kg/m² with a stable weight within past three months before study initiation

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Metyrapone And Hydrocortisone; Drug: Metyrapone 250 mg Oral Tablets During one phase of the study: Metyrapone (pills of 250mg) on full stomach: Day 1 0-1-2, day 2 1-2-2, day 3 3-3-4 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-0-0 Drug: Hydrocortisone 19,9mg/12mg s.c., pulsatile with a flow rate of 10μl/s Hydrocortisone will be delivered subcutaneously via a pump in a pulsed fashion with a flow rate of 10μl/s from day 1 to day 6 in a total daily dose of 19.9mg and 12mg on day 7
Placebo Comparator: 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.	Drug: Placebo; Drug: Placebo 250 mg Tablets During another phase of the study: identical looking placebo pills starting Day 1 During one phase of the study: Metyrapone (pills of 250mg) on full stomach: Day 1 0-1-2, day 2 1-2-2, day 3 3-3-4 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-0-0 Drug: Placebo (0,9% NaCl solution) Placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion with a flow rate of 10μl/s from day 1 to day 6 and 12mg on day 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total body fat	Change in total body fat assessed with a Dual-Energy-X-Ray-Absorptiometry (DXA)	Two 7-day intervention periods

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Satiation	Amount of food intake with ad libitum buffet	Two 7-day intervention periods
Total lean mass	Change in total lean mass assessed with DXA	Two 7-day intervention periods
Insulin sensitivity	Change in insulin sensitivity assessed with a mixed meal tolerance test	Two 7-day intervention periods
Glucose	Change in Glucose assessed with a mixed meal tolerance test	Two 7-day intervention periods
Insulin	Change in Insulin assessed with a mixed meal tolerance test	Two 7-day intervention periods
C-peptide	Change in C-peptide assessed with a mixed meal tolerance test	Two 7-day intervention periods
Energy expenditure	Basal metabolic rate measured with indirect calorimetryy	Two 7-day intervention periods
Substrate utilization	Respiratory quotient assessed with indirect calorimetry	Two 7-day intervention periods
Systolic and diastolic blood pressure	Assessment of blood pressure with a standard blood pressure monitor.	Two 7-day intervention periods
Weight	Measurement of weight with a standard scale	Two 7-day intervention periods
Lipids (mmol/l) ((total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides)	Blood sample	Two 7-day intervention periods
Immune cells (peripheral blood mononuclear cells)	Blood sample	Two 7-day intervention periods
Satiety	Appetite rating with visual analogue scale (VAS) from 0mm-100mm (0mm=not at all and 100mm=extreme)	Two 7-day intervention periods
Motivation	Motivation to eat measured with a speed clicking test	Two 7-day intervention periods
IL-6 (Inflammatory markers)	Blood sample	Two 7-day intervention periods
IL-1RA (Inflammatory markers)	Blood sample	Two 7-day intervention periods
IL-8 (Inflammatory markers)	Blood sample	Two 7-day intervention periods
CRP (Inflammatory markers)	Blood sample	Two 7-day intervention periods
Thyroid hormones	Blood sample	Two 7-day intervention periods
Growth hormone	Blood sample	Two 7-day intervention periods
IGF1	Blood sample	Two 7-day intervention periods
Catecholamines	Blood sample	Two 7-day intervention periods
GLP-1	Blood sample	Two 7-day intervention periods
GIP	Blood sample	Two 7-day intervention periods
Glucagon	Blood sample	Two 7-day intervention periods
PYY	Blood sample	Two 7-day intervention periods
CCK	Blood sample	Two 7-day intervention periods
FGF21	Blood sample	Two 7-day intervention periods
Leptin	Blood sample	Two 7-day intervention periods
Ghrelin	Blood sample	Two 7-day intervention periods
GDF15	Blood sample	Two 7-day intervention periods
Cortisol	Blood sample	Two 7-day intervention periods
Aldosterone	Blood sample	Two 7-day intervention periods
Renin	Blood sample	Two 7-day intervention periods
ACTH	Blood sample	Two 7-day intervention periods
Pregnenolone	Blood sample	Two 7-day intervention periods
Progesterone	Blood sample	Two 7-day intervention periods
11-deoxycorticosterone	Blood sample	Two 7-day intervention periods
Corticosterone	Blood sample	Two 7-day intervention periods
18-hydroxycorticosterone	Blood sample	Two 7-day intervention periods
17-hydroxypregnenolone	Blood sample	Two 7-day intervention periods
17-hydroxyprogesterone	Blood sample	Two 7-day intervention periods
11-deoxycortisol	Blood sample	Two 7-day intervention periods
Oxytocin	Blood sample	Two 7-day intervention periods

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Untargeted metabolomics of blood	Blood sample	Two 7-day intervention periods
Untargeted metabolomics of adipose tissue	Adipose tissue sample	Two 7-day intervention periods
Untargeted metabolomics of muscle	Muscle tissue sample	Two 7-day intervention periods
Gene expression analysis of adipose tissue	Adipose tissue sample	Two 7-day intervention periods
Gene expressions analysis of muscle tissue	Muscle tissue sample	Two 7-day intervention periods

Collaborators and Investigators

• Sponsor: Eleonora Seelig
• Investigators: Principal Investigator: Eleonora Seelig, PD Dr.med., Sponsor and principal investigator

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Actual): February 25, 2026
• Study Completion (Actual): February 25, 2026

Study Registration Dates

• First Submitted: July 17, 2024
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Signs and Symptoms, Digestive; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Hyperphagia; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Hydrocortisone; Metyrapone
• Other Study ID Numbers: EKNZ 2024-01381

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No