Clinical trial NCT05919992: The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation (Gluco-Starve)
Official title: The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Glucocorticoid Effect
Keywords: cortisol
glucocorticoids
starvation
caloric restriction
fasting
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2023-06-27
Enrollment: 24
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 fasting periods with each treatment. With the block and replace therapy, fasting-induced GC peak will be suppressed. Metabolic and autonomic parameters will be compared to reveal whether GCs mediate the physiological adaptions to caloric restriction.

Understanding acute effects of GCs upon caloric restriction is critical, since repetitive disruptions of GC secretion may become harmful in chronic conditions.

Detailed description: Obesity is one of the major causes of morbidity and mortality worldwide. Achieving long-term weight loss is challenging, as the body counteracts weight loss to preserve energy by increasing appetite and lowering energy expenditure. These physiological defense mechanisms are the main obstacle to successful weight reduction in obese people.

Therefore, identifying the signals that defend body weight during caloric restriction is essential for developing new antiobesity drugs. Corticosteroids mediate the physiological defense to starvation in rodents. Whether cortisol has the same impact on humans is unknown.

Therefore, we investigate whether cortisol regulates the physiological adaptions to caloric restriction in humans.

The general objective of this project is to investigate whether cortisol mediates physiological adaptions to caloric restriction.

The primary objective is to test whether cortisol mediates the increased appetite during caloric restriction.

Secondary objectives are to test whether the cortisol response to caloric restriction affects satiation, satiety, energy expenditure, substrate utilization, blood pressure, weight, body composition, secretion of neuroendocrine hormones, lipids, glucose, ketone bodies, sympathetic nervous system activity, immune cells, and inflammatory markers.

This is a double-blind, randomized, placebo-controlled crossover study.

After screening, subjects will be randomized to two crossover 7-day study periods with a wash-out 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 capsules per os (starting with a dose of 500 mg/d on day 1 to 3000mg/d on day 5, and then will be kept constant until day 7).

B) Participants will receive a placebo (0,9% NaCl solution) subcutaneously via a pump in a pulsed fashion and identical-looking placebo capsules per os with the same regimen as for metyrapone.

During both study periods, participants will undergo two days of caloric restriction.

Eligibility criteria: Inclusion Criteria:

* BMI 18.5 - 27 kg/m2
* Weight stability for 6 months prior to the trial (+/- 2kg)

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 trial within the past two months
* Intake of any drugs (prescribed, over the counter or recreational), within 48 hours of the study initiation
* Intake of any steroids (including topical or inhaler) six month prior to the study
* Known allergy to metyrapone or hydrocortisone
* Inability or unwillingness to provide informed consent

Primary outcomes:
measure: Satiation
timeFrame: Two 7-day intervention periods
Secondary outcomes:
measure: Satiety
timeFrame: Two 7-day intervention periods
measure: Food preference
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: Blood pressure
timeFrame: Two 7-day intervention periods
measure: Weight
timeFrame: Two 7-day intervention periods
measure: Body composition
timeFrame: Two 7-day intervention periods
measure: Neuroendocrine hormones
timeFrame: Two 7-day intervention periods
measure: Lipids
timeFrame: Two 7-day intervention periods
measure: Glucose
timeFrame: Two 7-day intervention periods
measure: Insulin sensitivity
timeFrame: Two 7-day intervention periods
measure: Ketone bodies
timeFrame: Two 7-day intervention periods
measure: Sympathetic nervous system activity
timeFrame: Two 7-day intervention periods
measure: Immune cells
timeFrame: Two 7-day intervention periods
measure: Inflammatory markers
timeFrame: Two 7-day intervention periods
measure: Motivation to eat
timeFrame: Two 7-day intervention periods
measure: Pleasure from eating
timeFrame: Two 7-day intervention periods
measure: Measure of behavioural approach and behavioural inhibition system
timeFrame: Two 7-day intervention periods
measure: Eating behaviour type
timeFrame: Two 7-day intervention periods
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel-Stadt
Study officials:
References: