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

NCT ID: NCT06556277

Last Updated: 2025-04-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-01
• Study Completion Date: 2026-07-31

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)

Conditions

Glucocorticoids; Overweight and Obesity; Overeating

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

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).

Group Type: EXPERIMENTAL

Metyrapone And Hydrocortisone

Intervention Type: 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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Eleonora Seelig

OTHER

Sponsor Role: lead

Responsible Party

Eleonora Seelig

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Eleonora Seelig, PD Dr.med.

Role: PRINCIPAL_INVESTIGATOR

Sponsor and principal investigator

Locations

University Hospital Basel

Basel, Canton of Basel-City, Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Eleonora Seelig, PD Dr.med.

Role: CONTACT

eleonora.seelig@usb.ch

0041 61 328 63 23

Gabriele Cypaite, MD

Role: CONTACT

gabriele.cypaite@usb.ch

0041613284578

Facility Contacts

Eleonora Seelig, PD Dr. med.

Role: primary

eleonora.seelig@usb.ch

0041 61 328 63 23

Gabriele Cypaite, MD

Role: backup

gabriele.cypaite@usb.ch

0041613284578

Other Identifiers

EKNZ 2024-01381

Identifier Type: -

Identifier Source: org_study_id