Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake

NCT06556277 | Completed

• 1 other identifier: EKNZ 2024-01381
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Overweight and Obesity; Glucocorticoids; Overeating

Outcome Measures

Primary Outcomes (1)

• Total body fat

  Change in total body fat assessed with a Dual-Energy-X-Ray-Absorptiometry (DXA)

  Two 7-day intervention periods

Secondary Outcomes (44)

• Total lean mass

  Two 7-day intervention periods

• Insulin sensitivity

  Two 7-day intervention periods

• Glucose

  Two 7-day intervention periods

• Insulin

  Two 7-day intervention periods

• C-peptide

  Two 7-day intervention periods

Other Outcomes (5)

• Untargeted metabolomics of blood

  Two 7-day intervention periods

• Untargeted metabolomics of adipose tissue

  Two 7-day intervention periods

• Untargeted metabolomics of muscle

  Two 7-day intervention periods

Study Arms (2)

Metyrapone And Hydrocortisone

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Metyrapone And Hydrocortisone DRUG

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

Metyrapone And Hydrocortisone

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Since hormone fluctuations associated with the menstrual cycle may alter cortisol levels, women will not be included in the study. Although diversity will be reduced and the statements of the study cannot be applied to the female sex, these strict inclusion criteria allow an optimal homogeneity and increase statistical power.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eleonora Seelig: lead

Study Sites (1)

University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

MeSH Terms

Conditions

Overweight; Obesity; Hyperphagia

Interventions

Metyrapone; Hydrocortisone

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Eleonora Seelig, PD Dr.med.

  Sponsor and principal investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Double-blind, randomized, placebo-controlled cross-over study

Study Record Dates

• First Submitted: July 17, 2024
• First Posted: August 16, 2024
• Study Start: September 1, 2024
• Primary Completion: February 25, 2026
• Study Completion: February 25, 2026
• Last Updated: March 3, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)