Clinical trial NCT05167084: Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals
Official title: Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals - A Double-blind, Randomized, Placebo-controlled Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Glucocorticoid Effect
Keywords: cortisol
overfeeding
glucocorticoids
insulin sensitivity
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2021-12-22
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, randomized, placebo-controlled cross-over study
Primary purpose: PREVENTION

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)

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

Primary outcomes:
measure: Insulin sensitivity
timeFrame: Two 8-day intervention periods
Secondary outcomes:
measure: Cortisol (nmol/l) total and free
timeFrame: Two 8-day intervention periods
measure: Renin
timeFrame: Two 8-day intervention periods
measure: Aldosterone (Adrenal Steroid Hormones)
timeFrame: Two 8-day intervention periods
measure: Pregnenolon (Adrenal Steroid Hormones)
timeFrame: Two 8-day intervention periods
measure: Progesteron (Adrenal Steroid Hormones)
timeFrame: Two 8-day intervention periods
measure: 11-Deoxycorticosteron (Adrenal Steroid Hormones)
timeFrame: Two 8-day intervention periods
measure: Corticosteron (Adrenal Steroid Hormones)
timeFrame: Two 8-day intervention periods
measure: 18-Hydroxycorticosteron (Adrenal Steroid Hormones)
timeFrame: Two 8-day intervention periods
measure: 17-Hydroxypregnenolon (Adrenal Steroid Hormones)
timeFrame: Two 8-day intervention periods
measure: 17-Hydroxyprogesteron (Adrenal Steroid Hormones)
timeFrame: Two 8-day intervention periods
measure: 11-Deoxycortisol (Adrenal Steroid Hormones)
timeFrame: Two 8-day intervention periods
measure: GLP-1 (nmol/l)
timeFrame: Two 8-day intervention periods
measure: GIP (nmol/l)
timeFrame: Two 8-day intervention periods
measure: PYY (pg/ml)
timeFrame: Two 8-day intervention periods
measure: T3 (nmol/l)
timeFrame: Two 8-day intervention periods
measure: T4 (nmol/l)
timeFrame: Two 8-day intervention periods
measure: TSH (mIU/l)
timeFrame: Two 8-day intervention periods
measure: HGH (mIU/l)
timeFrame: Two 8-day intervention periods
measure: Lipids (mmol/l) ((total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides)
timeFrame: Two 8-day intervention periods
measure: GDF-15 (pg/mL)
timeFrame: Two 8-day intervention periods
measure: Sympathetic nervous system activity
timeFrame: Two 8-day intervention periods
measure: Systolic and diastolic blood pressure
timeFrame: Two 8-day intervention periods
measure: Weight
timeFrame: Two 8-day intervention periods
measure: Energy expenditure
timeFrame: Two 8-day intervention periods
measure: Substrate utilisation
timeFrame: Two 8-day intervention periods
measure: Satiety
timeFrame: Two 8-day intervention periods
measure: Satiation
timeFrame: Two 8-day intervention periods
Other outcomes:
measure: IL-6 (Inflammatory markers)
timeFrame: Two 8-day intervention periods
measure: IL-1RA (Inflammatory markers)
timeFrame: Two 8-day intervention periods
measure: IL-8 (Inflammatory markers)
timeFrame: Two 8-day intervention periods
measure: CRP (Inflammatory markers)
timeFrame: Two 8-day intervention periods
measure: Metabolomics
timeFrame: Two 8-day intervention periods
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt
Study officials:
References: