Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals

NCT ID: NCT05167084

Last Updated: 2023-08-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-08
• Study Completion Date: 2023-06-08

Brief Summary

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.

Detailed 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)

Conditions

Glucocorticoid Effect

Study Design

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

Study Groups

Metyrapone And Hydrocortisone

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).

Group Type: EXPERIMENTAL

Metyrapone 250 mg Oral Tablets

Intervention Type: DRUG

During one phase of the study: Metyrapone (pills of 250mg) on full stomach: Day 1 0-1-1, day 2 1-2-2, day 3 2-2-3 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-3-4 day 8 3-0-0

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

Intervention Type: DRUG

Hydrocortisone will be delivered subcutaneously via a pump in a pulsed fashion with a flow rate of 10μl/s from day 1 to day 8 in a total daily dose of 19.9mg

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo 250 mg Tablets

Intervention Type: DRUG

During another phase of the study: identical looking placebo pills starting Day 1 0-1-1, day 2 1-2-2, day 3 2-2-3 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-3-4 day 8 3-0-0

Placebo (0,9% NaCl solution)

Intervention Type: DRUG

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 8

Interventions

Metyrapone 250 mg Oral Tablets

During one phase of the study: Metyrapone (pills of 250mg) on full stomach: Day 1 0-1-1, day 2 1-2-2, day 3 2-2-3 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-3-4 day 8 3-0-0

Intervention Type: DRUG

Placebo 250 mg Tablets

During another phase of the study: identical looking placebo pills starting Day 1 0-1-1, day 2 1-2-2, day 3 2-2-3 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-3-4 day 8 3-0-0

Intervention Type: DRUG

Hydrocortisone 19,9mg 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 8 in a total daily dose of 19.9mg

Intervention Type: 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 8

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 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

Locations

University Hospital Basel

Basel, Canton of Basel-City, Switzerland

Countries

Switzerland

Other Identifiers

EKNZ 2021-01507

Identifier Type: -

Identifier Source: org_study_id