Glucocorticoid EffectEarly Phase 1NCT05919992
The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation (Gluco-Starve)
A Early Phase 1 study testing Metyrapone 250 mg Oral Tablets and Hydrocortisone 19.9mg s.c., pulsatile with a flow rate of 10μl/s in people with Glucocorticoid Effect, run by Eleonora Seelig at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Glucocorticoid Effect
- What is being tested?
- Metyrapone 250 mg Oral Tablets and Hydrocortisone 19.9mg s.c., pulsatile with a flow rate of 10μl/s
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteSwitzerland
- Study dates
- 15 May 2023to 25 Jul 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- BMI 18.5 - 27 kg/m2
- Weight stability for 6 months prior to the trial (+/- 2kg)
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Basel
Basel, Canton of Basel-City, 4031
About this study
Official title: The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation
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.
Read the 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:
- 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).
- 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.
- Conditions
- Glucocorticoid Effect
- Being tested
- 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)
- Keywords
- cortisol, glucocorticoids, starvation, caloric restriction, fasting
- Medical subject headings
- Starvation, Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metyrapone 250 mg Oral TabletsDrug
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
Hydrocortisone 19.9mg s.c., pulsatile with a flow rate of 10μl/sDrug
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
Placebo 250 mg TabletsDrug
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
Placebo (0,9% NaCl solution)Drug
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
| Study group | Role | What they receive |
|---|---|---|
| Metyrapone And Hydrocortisone | Experimental | 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). Receives: Drug: Metyrapone 250 mg Oral Tablets; Drug: Hydrocortisone 19.9mg s.c., pulsatile with a flow rate of 10μl/s |
| Placebo | Placebo comparator | 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 Receives: Drug: Placebo 250 mg Tablets; Drug: Placebo (0,9% NaCl solution) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Satiation
Amount of food intake with ad libitum buffet
Measured: Two 7-day intervention periods
Secondary outcomes (19)
Satiety
Appetite rating by visual analog scale, minimum value 0, maximum value 100
Measured: Two 7-day intervention periods
Food preference
Amount of fat/ protein/carbohydrates consumed during ad libitum buffet
Measured: Two 7-day intervention periods
Energy expenditure
Basal metabolic rate, diet-induced thermogenesis
Measured: Two 7-day intervention periods
Substrate utilization
Respiratory quotient
Measured: Two 7-day intervention periods
Blood pressure
Blood pressure
Measured: Two 7-day intervention periods
Weight
Body weight
Measured: Two 7-day intervention periods
Body composition
measured with DEXA-Scans and body impedance analysis
Measured: Two 7-day intervention periods
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
Measured: Two 7-day intervention periods
Lipids
Total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides
Measured: Two 7-day intervention periods
Glucose
measured via blood sample
Measured: Two 7-day intervention periods
Insulin sensitivity
measured via blood sample
Measured: Two 7-day intervention periods
Ketone bodies
measured via blood sample
Measured: Two 7-day intervention periods
Sympathetic nervous system activity
measured via ECG: Heart rate, interbeat interval, high-frequency activity, low-frequency activity, root mean square of successive differences
Measured: Two 7-day intervention periods
Immune cells
Peripheral blood mononuclear cells (PBMCs)
Measured: Two 7-day intervention periods
Inflammatory markers
IL-6, IL-1RA, IL-8, CRP
Measured: Two 7-day intervention periods
Motivation to eat
clicking speed computer test
Measured: Two 7-day intervention periods
Pleasure from eating
Fonts rating test
Measured: Two 7-day intervention periods
Measure of behavioural approach and behavioural inhibition system
Questionnaire
Measured: Two 7-day intervention periods
Eating behaviour type
Questionnaire
Measured: Two 7-day intervention periods
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2023
- Study start15 May 2023
- Primary completion25 Jul 2024
- Study completion25 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glucocorticoid EffectStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind, randomized, placebo-controlled cross-over study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eleonora Seelig
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Eleonora Seelig, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05919992
- Sponsor's protocol ID
- EKNZ 2022-01837
- Status last verified
- Aug 2024
- First submitted
- 3 Mar 2023
- Last updated
- 14 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation
- ClinicalTrials.gov ID
- NCT05919992
- Acronym / sponsor ID
- EKNZ 2022-01837
- Conditions
- Glucocorticoid Effect
- Keywords
- cortisol, glucocorticoids, starvation, caloric restriction, fasting
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Eleonora SeeligUniversity, hospital or other
- Study start
- 15 May 2023 (actual)
- Primary completion
- 25 Jul 2024 (actual)
- Study completion
- 25 Jul 2024 (actual)
- First posted
- 27 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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).
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double-blind, randomized, placebo-controlled cross-over study
| Arm | Type | Receives |
|---|---|---|
| Metyrapone And Hydrocortisone | Experimental | Drug: Metyrapone 250 mg Oral Tablets, Drug: Hydrocortisone 19.9mg s.c., pulsatile with a flow rate of 10μl/sDuring 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). |
| Placebo | Placebo comparator | Drug: Placebo 250 mg Tablets, Drug: Placebo (0,9% NaCl solution)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 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- BMI 18.5 - 27 kg/m2
- Weight stability for 6 months prior to the trial (+/- 2kg)
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metyrapone 250 mg Oral TabletsDuring 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 | Drug | Metyrapone And Hydrocortisone |
| Hydrocortisone 19.9mg s.c., pulsatile with a flow rate of 10μl/sHydrocortisone 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 | Drug | Metyrapone And Hydrocortisone |
| Placebo 250 mg TabletsDuring 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 | Drug | Placebo |
| Placebo (0,9% NaCl solution)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 | Drug | Placebo |
Primary outcome
Satiation
Time frame: Two 7-day intervention periods
Amount of food intake with ad libitum buffet
19 secondary outcomes
Satiety
Time frame: Two 7-day intervention periods
Food preference
Time frame: Two 7-day intervention periods
Energy expenditure
Time frame: Two 7-day intervention periods
Substrate utilization
Time frame: Two 7-day intervention periods
Blood pressure
Time frame: Two 7-day intervention periods
Weight
Time frame: Two 7-day intervention periods
Body composition
Time frame: Two 7-day intervention periods
Neuroendocrine hormones
Time frame: Two 7-day intervention periods
Lipids
Time frame: Two 7-day intervention periods
Glucose
Time frame: Two 7-day intervention periods
Insulin sensitivity
Time frame: Two 7-day intervention periods
Ketone bodies
Time frame: Two 7-day intervention periods
Sympathetic nervous system activity
Time frame: Two 7-day intervention periods
Immune cells
Time frame: Two 7-day intervention periods
Inflammatory markers
Time frame: Two 7-day intervention periods
Motivation to eat
Time frame: Two 7-day intervention periods
Pleasure from eating
Time frame: Two 7-day intervention periods
Measure of behavioural approach and behavioural inhibition system
Time frame: Two 7-day intervention periods
Eating behaviour type
Time frame: Two 7-day intervention periods
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Metyrapone 250 mg Oral Tablets and Hydrocortisone 19.9mg s.c., pulsatile with a flow rate of 10μl/s in people with Glucocorticoid Effect, run by Eleonora Seelig at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Satiation (time frame: Two 7-day intervention periods). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2024.