Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals (Gluco-Feed)

Eleonora Seelig

Status and phase: Completed; Early Phase 1

Conditions: Glucocorticoid Effect

Treatments: Drug: Metyrapone 250 mg Oral Tablets; Drug: Hydrocortisone 19,9mg s.c., pulsatile with a flow rate of 10μl/s; Drug: Placebo (0,9% NaCl solution); Drug: Placebo 250 mg Tablets

Study type: Interventional

Funder types: Other

Identifiers

NCT05167084

EKNZ 2021-01507

Details and patient eligibility

About

In a randomized, cross-over study, 20 healthy volunteers 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 and autonomic parameters will be compared to reveal, whether GCs mediate the physiological adaptions to excessive food intake.

Understanding acute effects of GCs upon food intake is critical, since repetitive disruptions of GC secretion may become harmful in chronic conditions.

Full description

Obesity is one of the most serious health problems of the 21st century. To understand how we regulate our body weight is crucial for developing new treatment targets. Even though body mass index of populations is increasing, the body weight of adults is usually kept stable over time. Indeed, acute excessive food intake triggers a set of adaptions in order to prevent weight gain. The signal that triggers these beneficial adaptions is still unknown. Glucocorticoid (GC) secretion increases with acute food intake and many physiological adaptions to overfeeding coincide with classical glucocorticoid actions. The investigators therefore hypothesize that GCs are the signal that prevents weight gain during acute overfeeding.

The objective of this project is to test whether food-induced GCs represent the physiological signal that defends against weight gain.

The primary objective is to investigate whether reduction in insulin sensitivity is abolished with the block and replace therapy.

Secondary objectives are to investigate whether suppression of GC secretion during excessive food intake impairs the activation of sympathetic nervous system, satiety, satiation, energy expenditure, substrate utilization, blood pressure, secretion of neuroendocrine hormones, lipids and immune cells.

This is a double-blind, randomized, placebo-controlled cross-over study. After screening, subjects will be randomized to two crossover 8-day study periods with a washout period of 28 days:

A) Participants will receive hydrocortisone 19.9 mg/d subcutaneously via a pump in a pulsed fashion (eight times/day) and metyrapone per os (starting with a dose of 500 mg/d on day 1 to 2500mg/d on day 4, and then will be kept constant until day 8)

B) Participants will receive placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion and placebo pills per os (starting with a dose of 500 mg/d on day 1 to 2500mg/d on day 4, and then will be kept constant until day 8)

Enrollment: 20 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• BMI 18.5 - 25 kg/m2

Exclusion criteria

• Previous medical history for any chronic condition in the last three months, active disease or abnormal physical examination as verified by a qualified physician.
• Casual smoking (>6 cigarettes per day)
• Frequent, heavy alcohol consumption (>30g/day)
• Frequent, heavy caffeine consumption (>4 caffeinated drinks/day)
• Regular physical exercise (>4hrs per week)
• Shift workers
• Participation in an investigational drug trail within the past two months
• Intake of any drugs (prescribed, over the counter or recreational) including topical steroids and inhalers, within 48 hours of the study initiation
• Known allergy to metyrapone
• Inability or unwillingness to provide informed consent

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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20 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 subcutaneously via a pump in a pulsed fashion (eight times/day) and metyrapone per os (starting with a dose of 500 mg/d, then the dose will be increased the next days until 2500mg/d is achieved).

Treatment:

Drug: Metyrapone 250 mg Oral Tablets

Drug: Hydrocortisone 19,9mg s.c., pulsatile with a flow rate of 10μl/s

Placebo

Placebo Comparator group

Description:

During the other study period, subjects receive placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion and the same dose of placebo tablets p.o instead of metyrapone.

Treatment:

Drug: Placebo 250 mg Tablets

Drug: Placebo (0,9% NaCl solution)