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The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation (Gluco-Starve)

Primary Purpose

Glucocorticoid Effect

Status
Recruiting
Phase
Early Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Metyrapone 250 mg Oral Tablets
Hydrocortisone 19.9mg s.c., pulsatile with a flow rate of 10μl/s
Placebo 250 mg Tablets
Placebo (0,9% NaCl solution)
Sponsored by
Eleonora Seelig
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Glucocorticoid Effect focused on measuring cortisol, glucocorticoids, starvation, caloric restriction, fasting

Eligibility Criteria

18 Years - 40 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • University Hospital BaselRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Metyrapone And Hydrocortisone

Placebo

Arm Description

During one of the study periods, subjects 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, then the dose will be increased the next days until 3000mg/d is achieved).

During the other study period, subjects receive placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion and the same dose of placebo tablets p.o instead of metyrapone

Outcomes

Primary Outcome Measures

Satiation
Amount of food intake with ad libitum buffet

Secondary Outcome Measures

Satiety
Appetite rating by visual analog scale, minimum value 0, maximum value 100
Food preference
Amount of fat/ protein/carbohydrates consumed during ad libitum buffet
Energy expenditure
Basal metabolic rate, diet-induced thermogenesis
Substrate utilization
Respiratory quotient
Blood pressure
Blood pressure
Weight
Body weight
Body composition
measured with DEXA-Scans and body impedance analysis
Neuroendocrine hormones
Leptin, thyroid hormones, insulin, c-peptide, growth hormone, IGF1, catecholamines, GLP-1, GIP, glucagon, PYY, CCK, ghrelin, GDF-15, cortisol total and free, ACTH, renin, aldosterone, pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, 18-hydroxycorticosterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, oxytocin, FGF-21
Lipids
Total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides
Glucose
measured via blood sample
Insulin sensitivity
measured via blood sample
Ketone bodies
measured via blood sample
Sympathetic nervous system activity
measured via ECG: Heart rate, interbeat interval, high-frequency activity, low-frequency activity, root mean square of successive differences
Immune cells
Peripheral blood mononuclear cells (PBMCs)
Inflammatory markers
IL-6, IL-1RA, IL-8, CRP
Motivation to eat
clicking speed computer test
Pleasure from eating
Fonts rating test
Measure of behavioural approach and behavioural inhibition system
Questionnaire
Eating behaviour type
Questionnaire

Full Information

First Posted
March 3, 2023
Last Updated
June 15, 2023
Sponsor
Eleonora Seelig
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1. Study Identification

Unique Protocol Identification Number
NCT05919992
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 15, 2023 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Eleonora Seelig

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glucocorticoid Effect
Keywords
cortisol, glucocorticoids, starvation, caloric restriction, fasting

7. Study Design

Primary Purpose
Prevention
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Model Description
Double-blind, randomized, placebo-controlled cross-over study
Masking
ParticipantInvestigator
Masking Description
Placebo-controlled
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Metyrapone And Hydrocortisone
Arm Type
Experimental
Arm Description
During one of the study periods, subjects 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, then the dose will be increased the next days until 3000mg/d is achieved).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
During the other study period, subjects receive placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion and the same dose of placebo tablets p.o instead of metyrapone
Intervention Type
Drug
Intervention Name(s)
Metyrapone 250 mg Oral Tablets
Intervention Description
During one phase of the study: Metyrapone (pills of 250mg) on empty stomach: Day 1 0-1-1, day 2 1-2-2, day 3 2-3-3 day 4 3-4-4 day 5 4-4-4 day 6 4-4-4 day 7 4-0-0
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone 19.9mg s.c., pulsatile with a flow rate of 10μl/s
Intervention Description
Hydrocortisone will be delivered subcutaneously via a pump in a pulsed fashion with a flow rate of 10μl/s from day 1 to day 7 in a total daily dose of 19.9mg
Intervention Type
Drug
Intervention Name(s)
Placebo 250 mg Tablets
Intervention Description
During another phase of the study: identical looking placebo pills starting Day 1 0-1-1, day 2 1-2-2, day 3 2-3-3 day 4 3-4-4 day 5 4-4-4 day 6 4-4-4 day 7 4-0-0
Intervention Type
Drug
Intervention Name(s)
Placebo (0,9% NaCl solution)
Intervention Description
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 7
Primary Outcome Measure Information:
Title
Satiation
Description
Amount of food intake with ad libitum buffet
Time Frame
Two 7-day intervention periods
Secondary Outcome Measure Information:
Title
Satiety
Description
Appetite rating by visual analog scale, minimum value 0, maximum value 100
Time Frame
Two 7-day intervention periods
Title
Food preference
Description
Amount of fat/ protein/carbohydrates consumed during ad libitum buffet
Time Frame
Two 7-day intervention periods
Title
Energy expenditure
Description
Basal metabolic rate, diet-induced thermogenesis
Time Frame
Two 7-day intervention periods
Title
Substrate utilization
Description
Respiratory quotient
Time Frame
Two 7-day intervention periods
Title
Blood pressure
Description
Blood pressure
Time Frame
Two 7-day intervention periods
Title
Weight
Description
Body weight
Time Frame
Two 7-day intervention periods
Title
Body composition
Description
measured with DEXA-Scans and body impedance analysis
Time Frame
Two 7-day intervention periods
Title
Neuroendocrine hormones
Description
Leptin, thyroid hormones, insulin, c-peptide, growth hormone, IGF1, catecholamines, GLP-1, GIP, glucagon, PYY, CCK, ghrelin, GDF-15, cortisol total and free, ACTH, renin, aldosterone, pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, 18-hydroxycorticosterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, oxytocin, FGF-21
Time Frame
Two 7-day intervention periods
Title
Lipids
Description
Total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides
Time Frame
Two 7-day intervention periods
Title
Glucose
Description
measured via blood sample
Time Frame
Two 7-day intervention periods
Title
Insulin sensitivity
Description
measured via blood sample
Time Frame
Two 7-day intervention periods
Title
Ketone bodies
Description
measured via blood sample
Time Frame
Two 7-day intervention periods
Title
Sympathetic nervous system activity
Description
measured via ECG: Heart rate, interbeat interval, high-frequency activity, low-frequency activity, root mean square of successive differences
Time Frame
Two 7-day intervention periods
Title
Immune cells
Description
Peripheral blood mononuclear cells (PBMCs)
Time Frame
Two 7-day intervention periods
Title
Inflammatory markers
Description
IL-6, IL-1RA, IL-8, CRP
Time Frame
Two 7-day intervention periods
Title
Motivation to eat
Description
clicking speed computer test
Time Frame
Two 7-day intervention periods
Title
Pleasure from eating
Description
Fonts rating test
Time Frame
Two 7-day intervention periods
Title
Measure of behavioural approach and behavioural inhibition system
Description
Questionnaire
Time Frame
Two 7-day intervention periods
Title
Eating behaviour type
Description
Questionnaire
Time Frame
Two 7-day intervention periods

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eleonora Seelig, MD
Phone
0041 61 328 63 23
Email
eleonora.seelig@usb.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Stéphanie Pfammatter
Phone
0041 61 328 45 79
Email
stephanie.pfammatter@usb.ch
Facility Information:
Facility Name
University Hospital Basel
City
Basel
State/Province
Basel-Stadt
ZIP/Postal Code
4031
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eleonora Seelig, MD
Phone
0041 61 328 63 23
Email
eleonora.seelig@usb.ch
First Name & Middle Initial & Last Name & Degree
Stéphanie Pfammatter
Phone
0041 61 328 45 79
Email
stephanie.pfammatter@usb.ch
First Name & Middle Initial & Last Name & Degree
Eleonora Seelig, MD
First Name & Middle Initial & Last Name & Degree
Stéphanie Pfammatter

12. IPD Sharing Statement

Plan to Share IPD
No

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The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation (Gluco-Starve)

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