Acute Consequences of Glucocorticoid Secretion in Overweight and Obese Individuals During Maximum Calorie Intake: a Double-blind, Randomized, Placebo-controlled, Cross-over Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- Total body fat
Study Overview
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)
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Metyrapone And Hydrocortisone
During one of the study periods, subjects receive hydrocortisone 19.9 mg/d day 1 to day 6 and 12 mg/d on day 7 subcutaneously via a pump in a pulsed fashion (eight times/day) and metyrapone per os (starting with a dose of 750 mg/d, then the dose will be increased on day 3, where 2500mg/d is achieved and reduced on day 7 to 750mg).
Intervention: Metyrapone And Hydrocortisone (Drug)
Placebo
During the other study period, subjects receive placebo (0,9% NaCl solution) the same dose of placebo instead of hydrocortisone subcutaneously via a pump in a pulsed fashion and the same dose of placebo tablets p.o instead of metyrapone.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Total body fat
Time Frame: Two 7-day intervention periods
Change in total body fat assessed with a Dual-Energy-X-Ray-Absorptiometry (DXA)
Secondary Outcomes
- Catecholamines(Two 7-day intervention periods)
- GIP(Two 7-day intervention periods)
- CCK(Two 7-day intervention periods)
- FGF21(Two 7-day intervention periods)
- Cortisol(Two 7-day intervention periods)
- Aldosterone(Two 7-day intervention periods)
- Pregnenolone(Two 7-day intervention periods)
- Total lean mass(Two 7-day intervention periods)
- Insulin(Two 7-day intervention periods)
- Energy expenditure(Two 7-day intervention periods)
- Immune cells (peripheral blood mononuclear cells)(Two 7-day intervention periods)
- Satiation(Two 7-day intervention periods)
- IL-6 (Inflammatory markers)(Two 7-day intervention periods)
- Insulin sensitivity(Two 7-day intervention periods)
- Systolic and diastolic blood pressure(Two 7-day intervention periods)
- GLP-1(Two 7-day intervention periods)
- Glucagon(Two 7-day intervention periods)
- Glucose(Two 7-day intervention periods)
- C-peptide(Two 7-day intervention periods)
- Substrate utilization(Two 7-day intervention periods)
- Weight(Two 7-day intervention periods)
- Motivation(Two 7-day intervention periods)
- IL-1RA (Inflammatory markers)(Two 7-day intervention periods)
- CRP (Inflammatory markers)(Two 7-day intervention periods)
- Thyroid hormones(Two 7-day intervention periods)
- Leptin(Two 7-day intervention periods)
- IGF1(Two 7-day intervention periods)
- Lipids (mmol/l) ((total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides)(Two 7-day intervention periods)
- Satiety(Two 7-day intervention periods)
- IL-8 (Inflammatory markers)(Two 7-day intervention periods)
- Growth hormone(Two 7-day intervention periods)
- Ghrelin(Two 7-day intervention periods)
- GDF15(Two 7-day intervention periods)
- PYY(Two 7-day intervention periods)
- Renin(Two 7-day intervention periods)
- ACTH(Two 7-day intervention periods)
- Progesterone(Two 7-day intervention periods)
- 17-hydroxyprogesterone(Two 7-day intervention periods)
- 11-deoxycorticosterone(Two 7-day intervention periods)
- Corticosterone(Two 7-day intervention periods)
- 18-hydroxycorticosterone(Two 7-day intervention periods)
- 17-hydroxypregnenolone(Two 7-day intervention periods)
- 11-deoxycortisol(Two 7-day intervention periods)
- Oxytocin(Two 7-day intervention periods)
Investigators
Eleonora Seelig
Principal Investigator
University Hospital, Basel, Switzerland