Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals

Glucocorticoid Effect Clinical Trial

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Official title:

Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals - A Double-blind, Randomized, Placebo-controlled Cross-over Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05167084
• Other study ID #: EKNZ 2021-01507
• Status: Completed
• Phase: Early Phase 1
• Start date: February 8, 2022
• Est. completion date: June 8, 2023

Study information

• Verified date: August 2023
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 8, 2023
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Glucocorticoid Effect

Intervention

Drug:
• 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
• 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
• 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
• 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

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel	Basel-Stadt

Sponsors (1)

Lead Sponsor	Collaborator
Eleonora Seelig

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	IL-6 (Inflammatory markers)	Blood Sample	Two 8-day intervention periods
Other	IL-1RA (Inflammatory markers)	Blood Sample	Two 8-day intervention periods
Other	IL-8 (Inflammatory markers)	Blood Sample	Two 8-day intervention periods
Other	CRP (Inflammatory markers)	Blood Sample	Two 8-day intervention periods
Other	Metabolomics	Metabolomics will be performed in blood plasma	Two 8-day intervention periods
Primary	Insulin sensitivity	Change in insulin sensitivity assessed with a mixed meal tolerance test	Two 8-day intervention periods
Secondary	Cortisol (nmol/l) total and free	Blood sample	Two 8-day intervention periods
Secondary	Renin	Blood Sample	Two 8-day intervention periods
Secondary	Aldosterone (Adrenal Steroid Hormones)	Blood Sample	Two 8-day intervention periods
Secondary	Pregnenolon (Adrenal Steroid Hormones)	Blood Sample	Two 8-day intervention periods
Secondary	Progesteron (Adrenal Steroid Hormones)	Blood Sample	Two 8-day intervention periods
Secondary	11-Deoxycorticosteron (Adrenal Steroid Hormones)	Blood Sample	Two 8-day intervention periods
Secondary	Corticosteron (Adrenal Steroid Hormones)	Blood Sample	Two 8-day intervention periods
Secondary	18-Hydroxycorticosteron (Adrenal Steroid Hormones)	Blood Sample	Two 8-day intervention periods
Secondary	17-Hydroxypregnenolon (Adrenal Steroid Hormones)	Blood Sample	Two 8-day intervention periods
Secondary	17-Hydroxyprogesteron (Adrenal Steroid Hormones)	Blood Sample	Two 8-day intervention periods
Secondary	11-Deoxycortisol (Adrenal Steroid Hormones)	Blood Sample	Two 8-day intervention periods
Secondary	GLP-1 (nmol/l)	Blood sample	Two 8-day intervention periods
Secondary	GIP (nmol/l)	Blood Sample	Two 8-day intervention periods
Secondary	PYY (pg/ml)	Blood Sample	Two 8-day intervention periods
Secondary	T3 (nmol/l)	Blood Sample	Two 8-day intervention periods
Secondary	T4 (nmol/l)	Blood Sample	Two 8-day intervention periods
Secondary	TSH (mIU/l)	Blood Sample	Two 8-day intervention periods
Secondary	HGH (mIU/l)	Blood Sample	Two 8-day intervention periods
Secondary	Lipids (mmol/l) ((total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides)	Blood Sample	Two 8-day intervention periods
Secondary	GDF-15 (pg/mL)	Blood Sample	Two 8-day intervention periods
Secondary	Sympathetic nervous system activity	Heart rate variability analysis	Two 8-day intervention periods
Secondary	Systolic and diastolic blood pressure	Assessment of blood pressure with a standard blood pressure monitor.	Two 8-day intervention periods
Secondary	Weight	Measurement of weight with a standard scale	Two 8-day intervention periods
Secondary	Energy expenditure	Basal metabolic rate measured with indirect calorimetry	Two 8-day intervention periods
Secondary	Substrate utilisation	Respiratory quotient assessed with indirect calorimetry	Two 8-day intervention periods
Secondary	Satiety	Appetite rating with visual analogue scale (VAS) from 0mm-100mm (0mm=not at all and 100mm=extreme)	Two 8-day intervention periods
Secondary	Satiation	Amount of food intake with ad libitum buffet	Two 8-day intervention periods