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

Eleonora Seelig

Status: Enrolling

Conditions: Overeating; Overweight and Obesity; Glucocorticoids

Treatments: Drug: Metyrapone And Hydrocortisone; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06556277

EKNZ 2024-01381

Details and patient eligibility

About

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.

Full 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)

Enrollment: 23 estimated patients

Sex: Male

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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23 participants in 2 patient groups, including a placebo group

Metyrapone And Hydrocortisone

Experimental group

Description:

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).

Treatment:

Drug: Metyrapone And Hydrocortisone

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo