Glucocorticoid EffectEarly Phase 1Gluco-FeedNCT05167084
Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals
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 overfeeding 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
- 20 participants
- Where
- 1 siteSwitzerland
- Study dates
- 8 Feb 2022to 8 Jun 2023
- 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 - 25 kg/m2
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 10Show fewer
- Participation in an investigational drug trail within the past two months
- Intake of any drugs (prescribed, over the counter or recreational) including topical steroids and inhalers, within 48 hours of the study initiation
- Known allergy to metyrapone
- 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: Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals - A Double-blind, Randomized, Placebo-controlled Cross-over Study
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 overfeeding periods with each treatment. With the block and replace therapy, food-induced GC peak will be suppressed. Metabolic and autonomic parameters will be compared to reveal, whether GCs mediate the physiological adaptions to excessive food intake.
Understanding acute effects of GCs upon food intake is critical, since repetitive disruptions of GC secretion may become harmful in chronic conditions.
Read the detailed description
Obesity is one of the most serious health problems of the 21st century. To understand how we regulate our body weight is crucial for developing new treatment targets. Even though body mass index of populations is increasing, the body weight of adults is usually kept stable over time. Indeed, acute excessive food intake triggers a set of adaptions in order to prevent weight gain. The signal that triggers these beneficial adaptions is still unknown. Glucocorticoid (GC) secretion increases with acute food intake and many physiological adaptions to overfeeding coincide with classical glucocorticoid actions. The investigators therefore hypothesize that GCs are the signal that prevents weight gain during acute overfeeding.
The objective of this project is to test whether food-induced GCs represent the physiological signal that defends against weight gain.
The primary objective is to investigate whether reduction in insulin sensitivity is abolished with the block and replace therapy.
Secondary objectives are to investigate whether suppression of GC secretion during excessive food intake impairs the activation of sympathetic nervous system, satiety, satiation, energy expenditure, substrate utilization, blood pressure, secretion of neuroendocrine hormones, lipids and immune cells.
This is a double-blind, randomized, placebo-controlled cross-over study. After screening, subjects will be randomized to two crossover 8-day study periods with a washout 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 per os (starting with a dose of 500 mg/d on day 1 to 2500mg/d on day 4, and then will be kept constant until day 8)
- Participants will receive placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion and placebo pills per os (starting with a dose of 500 mg/d on day 1 to 2500mg/d on day 4, and then will be kept constant until day 8)
- Conditions
- Glucocorticoid Effect
- Being tested
- Metyrapone 250 mg Oral Tablets, Placebo 250 mg Tablets, Hydrocortisone 19,9mg s.c., pulsatile with a flow rate of 10μl/s, Placebo (0,9% NaCl solution)
- Keywords
- cortisol, overfeeding, glucocorticoids, insulin sensitivity
- Medical subject headings
- Insulin Resistance
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 full stomach: Day 1 0-1-1, day 2 1-2-2, day 3 2-2-3 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-3-4 day 8 3-0-0
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 2-2-3 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-3-4 day 8 3-0-0
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 8 in a total daily dose of 19.9mg
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 8
| 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 2500mg/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.
Insulin sensitivity
Change in insulin sensitivity assessed with a mixed meal tolerance test
Measured: Two 8-day intervention periods
Secondary outcomes (27)
Cortisol (nmol/l) total and free
Blood sample
Measured: Two 8-day intervention periods
Renin
Blood Sample
Measured: Two 8-day intervention periods
Aldosterone (Adrenal Steroid Hormones)
Blood Sample
Measured: Two 8-day intervention periods
Pregnenolon (Adrenal Steroid Hormones)
Blood Sample
Measured: Two 8-day intervention periods
Progesteron (Adrenal Steroid Hormones)
Blood Sample
Measured: Two 8-day intervention periods
11-Deoxycorticosteron (Adrenal Steroid Hormones)
Blood Sample
Measured: Two 8-day intervention periods
Corticosteron (Adrenal Steroid Hormones)
Blood Sample
Measured: Two 8-day intervention periods
18-Hydroxycorticosteron (Adrenal Steroid Hormones)
Blood Sample
Measured: Two 8-day intervention periods
17-Hydroxypregnenolon (Adrenal Steroid Hormones)
Blood Sample
Measured: Two 8-day intervention periods
17-Hydroxyprogesteron (Adrenal Steroid Hormones)
Blood Sample
Measured: Two 8-day intervention periods
11-Deoxycortisol (Adrenal Steroid Hormones)
Blood Sample
Measured: Two 8-day intervention periods
GLP-1 (nmol/l)
Blood sample
Measured: Two 8-day intervention periods
GIP (nmol/l)
Blood Sample
Measured: Two 8-day intervention periods
PYY (pg/ml)
Blood Sample
Measured: Two 8-day intervention periods
T3 (nmol/l)
Blood Sample
Measured: Two 8-day intervention periods
T4 (nmol/l)
Blood Sample
Measured: Two 8-day intervention periods
TSH (mIU/l)
Blood Sample
Measured: Two 8-day intervention periods
HGH (mIU/l)
Blood Sample
Measured: Two 8-day intervention periods
Lipids (mmol/l) ((total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides)
Blood Sample
Measured: Two 8-day intervention periods
GDF-15 (pg/mL)
Blood Sample
Measured: Two 8-day intervention periods
Sympathetic nervous system activity
Heart rate variability analysis
Measured: Two 8-day intervention periods
Systolic and diastolic blood pressure
Assessment of blood pressure with a standard blood pressure monitor.
Measured: Two 8-day intervention periods
Weight
Measurement of weight with a standard scale
Measured: Two 8-day intervention periods
Energy expenditure
Basal metabolic rate measured with indirect calorimetry
Measured: Two 8-day intervention periods
Substrate utilisation
Respiratory quotient assessed with indirect calorimetry
Measured: Two 8-day intervention periods
Satiety
Appetite rating with visual analogue scale (VAS) from 0mm-100mm (0mm=not at all and 100mm=extreme)
Measured: Two 8-day intervention periods
Satiation
Amount of food intake with ad libitum buffet
Measured: Two 8-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 posted22 Dec 2021
- Study start8 Feb 2022
- Primary completion8 Jun 2023
- Study completion8 Jun 2023
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
- 20 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
- NCT05167084
- Sponsor's protocol ID
- EKNZ 2021-01507
- Acronym
- Gluco-Feed
- Status last verified
- Aug 2023
- First submitted
- 8 Dec 2021
- Last updated
- 23 Aug 2023
- 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 23 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals - A Double-blind, Randomized, Placebo-controlled Cross-over Study
- ClinicalTrials.gov ID
- NCT05167084
- Acronym / sponsor ID
- Gluco-Feed / EKNZ 2021-01507
- Conditions
- Glucocorticoid Effect
- Keywords
- cortisol, overfeeding, glucocorticoids, insulin sensitivity
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Eleonora SeeligUniversity, hospital or other
- Study start
- 8 Feb 2022 (actual)
- Primary completion
- 8 Jun 2023 (actual)
- Study completion
- 8 Jun 2023 (actual)
- First posted
- 22 Dec 2021 (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 overfeeding periods with each treatment. With the block and replace therapy, food-induced GC peak will be suppressed. Metabolic and autonomic parameters will be compared to reveal, whether GCs mediate the physiological adaptions to excessive food intake.
Understanding acute effects of GCs upon food intake is critical, since repetitive disruptions of GC secretion may become harmful in chronic conditions.
Detailed description
Obesity is one of the most serious health problems of the 21st century. To understand how we regulate our body weight is crucial for developing new treatment targets. Even though body mass index of populations is increasing, the body weight of adults is usually kept stable over time. Indeed, acute excessive food intake triggers a set of adaptions in order to prevent weight gain. The signal that triggers these beneficial adaptions is still unknown. Glucocorticoid (GC) secretion increases with acute food intake and many physiological adaptions to overfeeding coincide with classical glucocorticoid actions. The investigators therefore hypothesize that GCs are the signal that prevents weight gain during acute overfeeding.
The objective of this project is to test whether food-induced GCs represent the physiological signal that defends against weight gain.
The primary objective is to investigate whether reduction in insulin sensitivity is abolished with the block and replace therapy.
Secondary objectives are to investigate whether suppression of GC secretion during excessive food intake impairs the activation of sympathetic nervous system, satiety, satiation, energy expenditure, substrate utilization, blood pressure, secretion of neuroendocrine hormones, lipids and immune cells.
This is a double-blind, randomized, placebo-controlled cross-over study. After screening, subjects will be randomized to two crossover 8-day study periods with a washout 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 per os (starting with a dose of 500 mg/d on day 1 to 2500mg/d on day 4, and then will be kept constant until day 8)
- Participants will receive placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion and placebo pills per os (starting with a dose of 500 mg/d on day 1 to 2500mg/d on day 4, and then will be kept constant until day 8)
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 2500mg/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 (1 listed)
- BMI 18.5 - 25 kg/m2
Key exclusion criteria (10 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 full stomach: Day 1 0-1-1, day 2 1-2-2, day 3 2-2-3 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-3-4 day 8 3-0-0 | 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 2-2-3 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-3-4 day 8 3-0-0 | Drug | Placebo |
| 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 8 in a total daily dose of 19.9mg | Drug | Metyrapone And Hydrocortisone |
| 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 8 | Drug | Placebo |
Primary outcome
Insulin sensitivity
Time frame: Two 8-day intervention periods
Change in insulin sensitivity assessed with a mixed meal tolerance test
27 secondary outcomes
Cortisol (nmol/l) total and free
Time frame: Two 8-day intervention periods
Renin
Time frame: Two 8-day intervention periods
Aldosterone (Adrenal Steroid Hormones)
Time frame: Two 8-day intervention periods
Pregnenolon (Adrenal Steroid Hormones)
Time frame: Two 8-day intervention periods
Progesteron (Adrenal Steroid Hormones)
Time frame: Two 8-day intervention periods
11-Deoxycorticosteron (Adrenal Steroid Hormones)
Time frame: Two 8-day intervention periods
Corticosteron (Adrenal Steroid Hormones)
Time frame: Two 8-day intervention periods
18-Hydroxycorticosteron (Adrenal Steroid Hormones)
Time frame: Two 8-day intervention periods
17-Hydroxypregnenolon (Adrenal Steroid Hormones)
Time frame: Two 8-day intervention periods
17-Hydroxyprogesteron (Adrenal Steroid Hormones)
Time frame: Two 8-day intervention periods
11-Deoxycortisol (Adrenal Steroid Hormones)
Time frame: Two 8-day intervention periods
GLP-1 (nmol/l)
Time frame: Two 8-day intervention periods
GIP (nmol/l)
Time frame: Two 8-day intervention periods
PYY (pg/ml)
Time frame: Two 8-day intervention periods
T3 (nmol/l)
Time frame: Two 8-day intervention periods
T4 (nmol/l)
Time frame: Two 8-day intervention periods
TSH (mIU/l)
Time frame: Two 8-day intervention periods
HGH (mIU/l)
Time frame: Two 8-day intervention periods
Lipids (mmol/l) ((total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides)
Time frame: Two 8-day intervention periods
GDF-15 (pg/mL)
Time frame: Two 8-day intervention periods
Sympathetic nervous system activity
Time frame: Two 8-day intervention periods
Systolic and diastolic blood pressure
Time frame: Two 8-day intervention periods
Weight
Time frame: Two 8-day intervention periods
Energy expenditure
Time frame: Two 8-day intervention periods
Substrate utilisation
Time frame: Two 8-day intervention periods
Satiety
Time frame: Two 8-day intervention periods
Satiation
Time frame: Two 8-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 23 Aug 2023.
- 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 1 inclusion and 10 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 23 Aug 2023. 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?
Insulin sensitivity (time frame: Two 8-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 23 Aug 2023.