Clinical trial NCT06556277: Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake
Official title: Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake: a Double-blind, Randomized, Placebo-controlled, Cross-over Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Glucocorticoids
Overweight and Obesity
Overeating
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2024-08-16
Enrollment: 23
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
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: OTHER

Brief summary: 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.

Detailed 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)

Eligibility criteria: 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

Primary outcomes:
measure: Total body fat
timeFrame: Two 7-day intervention periods
Secondary outcomes:
measure: Total lean mass
timeFrame: Two 7-day intervention periods
measure: Insulin sensitivity
timeFrame: Two 7-day intervention periods
measure: Glucose
timeFrame: Two 7-day intervention periods
measure: Insulin
timeFrame: Two 7-day intervention periods
measure: C-peptide
timeFrame: Two 7-day intervention periods
measure: Energy expenditure
timeFrame: Two 7-day intervention periods
measure: Substrate utilization
timeFrame: Two 7-day intervention periods
measure: Systolic and diastolic blood pressure
timeFrame: Two 7-day intervention periods
measure: Weight
timeFrame: Two 7-day intervention periods
measure: Lipids (mmol/l) ((total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides)
timeFrame: Two 7-day intervention periods
measure: Immune cells (peripheral blood mononuclear cells)
timeFrame: Two 7-day intervention periods
measure: Satiation
timeFrame: Two 7-day intervention periods
measure: Satiety
timeFrame: Two 7-day intervention periods
measure: Motivation
timeFrame: Two 7-day intervention periods
measure: IL-6 (Inflammatory markers)
timeFrame: Two 7-day intervention periods
measure: IL-1RA (Inflammatory markers)
timeFrame: Two 7-day intervention periods
measure: IL-8 (Inflammatory markers)
timeFrame: Two 7-day intervention periods
measure: CRP (Inflammatory markers)
timeFrame: Two 7-day intervention periods
measure: Thyroid hormones
timeFrame: Two 7-day intervention periods
measure: Growth hormone
timeFrame: Two 7-day intervention periods
measure: IGF1
timeFrame: Two 7-day intervention periods
measure: Catecholamines
timeFrame: Two 7-day intervention periods
measure: GLP-1
timeFrame: Two 7-day intervention periods
measure: GIP
timeFrame: Two 7-day intervention periods
measure: Glucagon
timeFrame: Two 7-day intervention periods
measure: PYY
timeFrame: Two 7-day intervention periods
measure: CCK
timeFrame: Two 7-day intervention periods
measure: FGF21
timeFrame: Two 7-day intervention periods
measure: Leptin
timeFrame: Two 7-day intervention periods
measure: Ghrelin
timeFrame: Two 7-day intervention periods
measure: GDF15
timeFrame: Two 7-day intervention periods
measure: Cortisol
timeFrame: Two 7-day intervention periods
measure: Aldosterone
timeFrame: Two 7-day intervention periods
measure: Renin
timeFrame: Two 7-day intervention periods
measure: ACTH
timeFrame: Two 7-day intervention periods
measure: Pregnenolone
timeFrame: Two 7-day intervention periods
measure: Progesterone
timeFrame: Two 7-day intervention periods
measure: 11-deoxycorticosterone
timeFrame: Two 7-day intervention periods
measure: Corticosterone
timeFrame: Two 7-day intervention periods
measure: 18-hydroxycorticosterone
timeFrame: Two 7-day intervention periods
measure: 17-hydroxypregnenolone
timeFrame: Two 7-day intervention periods
measure: 17-hydroxyprogesterone
timeFrame: Two 7-day intervention periods
measure: 11-deoxycortisol
timeFrame: Two 7-day intervention periods
measure: Oxytocin
timeFrame: Two 7-day intervention periods
Other outcomes:
measure: Untargeted metabolomics of blood
timeFrame: Two 7-day intervention periods
measure: Untargeted metabolomics of adipose tissue
timeFrame: Two 7-day intervention periods
measure: Untargeted metabolomics of muscle
timeFrame: Two 7-day intervention periods
measure: Gene expression analysis of adipose tissue
timeFrame: Two 7-day intervention periods
measure: Gene expressions analysis of muscle tissue
timeFrame: Two 7-day intervention periods
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt
Study officials:
affiliation: Sponsor and principal investigator
name: Eleonora Seelig, PD Dr.med.
role: PRINCIPAL_INVESTIGATOR
References: