Metabolic SyndromePhase 3CortILNCT02227420
Effects of IL-1 Beta on the HPA-axis in Obese Persons
A Phase 3 study testing Anakinra in people with Metabolic Syndrome and Hypersecretion; Cortisol, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
In obese individuals cortisol production and secretion is increased but the underlying mechanism is not known. Obesity leads to a pathological activation of the innate immune system partly driven by tissue production of IL-1β. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Metabolic Syndrome, Hypersecretion; Cortisol
- What is being tested?
- Anakinra
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 1 siteSwitzerland
- Study dates
- Oct 2014to Jul 2016
- Phase
- Phase 3
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-80 years
- BMI >30kg/m2 and at least 1 manifestations of the metabolic syndrome (i.e. diabetes/ prediabetes, hypertension, dyslipidemia)
- Willingness to use contraceptive measures adequate to prevent becoming pregnant
Who cannot join
- Medication with glucocorticosteroids
- Known Cushing Syndrome
- Pregnancy or breast feeding
- Clinical signs of infection in the week before inclusion or history of a severe infection during the last 2 months
- Hematologic disease (leukocyte count < 1.5x109/l, hemoglobin <11 g/dl, platelets <100 x 103/ul)
- Kidney disease (creatinine-clearance < 30ml/min))
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- Liver disease (transaminases >4x upper normal range)
- Active carcinoma
- History of tuberculosis
- Alcohol consumption >40g/d for men, >30g/d for women
- Known allergy towards anakinra
- Subject refusing or unable to give written informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of IL-1 Beta on the Hypothalamic-pituitary-adrenal (HPA) Axis in Obese Persons - the CortIL-Study
In obese individuals cortisol production and secretion is increased but the underlying mechanism is not known. Obesity leads to a pathological activation of the innate immune system partly driven by tissue production of IL-1β. Furthermore, IL-1β is also known to stimulate the release of adrenocorticotropin hormone (ACTH). Therefore, the investigators hypothesise that in obese individuals tissue inflammation stimulates ACTH via IL-1β, thereby explaining the observed hypercortisolism.
- Conditions
- Metabolic Syndrome, Hypersecretion; Cortisol
- Being tested
- Anakinra
- Medical subject headings
- Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnakinraDrug
Anakinra 100mg s.c. x 5
| Study group | Role | What they receive |
|---|---|---|
| Anakinra | Experimental | Anakinra 100mg s.c. x 5 Receives: Drug: Anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Morning cortisol levels
Measured: 14 days
Secondary outcomes (5)
effect of anakinra/Kineret® on salivary cortisol, free urinary cortisol, and serum cortisol levels after an overnight dexamethasone suppression test
Measured: 14 days
correlation between the percentage of body fat or body mass index, and suppression of cortisol levels after injection of anakinra/Kineret®
Measured: 14 days
correlation between inflammatory parameters with cortisol levels
Measured: 14 days
impact of anakinra/Kineret® on other pituitary and peripheral hormones, such as: ACTH, TSH, fT4, GH, IGF-1, LH, FSH, testosterone copeptin, IL-6, CRP, leukocyte count and body temperature.
impact of anakinra/Kineret® on other pituitary and peripheral hormones such as: ACTH, thyroid-stimulating Hormone (TSH), free thyroxine 4 (fT4), growth Hormone (GH), insulin like growth factor (IGF)-1, luteinizing Hormone (LH), follicle stimulating Hormone (FSH), testosterone copeptin, interleukin (IL)-6, C reactive protein (CRP), leukocyte count and body temperature.
Measured: 14 days
comparison of 1mg and 2mg dexamethasone suppression test
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2014 (estimated)
- Study startOct 2014
- Primary completionMar 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- 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
- Phase 3
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mirjam Christ-Crain, MD, Prof., Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02227420
- Sponsor's protocol ID
- EKNZ 2014-175
- Acronym
- CortIL
- Status last verified
- Aug 2016
- First submitted
- 26 Aug 2014
- Last updated
- 23 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Urwyler SA, Ebrahimi F, Burkard T, Schuetz P, Poglitsch M, Mueller B, Donath MY, Christ-Crain M. IL (Interleukin)-1 Receptor Antagonist Increases Ang (Angiotensin [1-7]) and Decreases Blood Pressure in Obese Individuals. Hypertension. 2020 Jun;75(6):1455-1463. doi: 10.1161/HYPERTENSIONAHA.119.13982. Epub 2020 Apr 10.
PubMed 32275191Urwyler SA, Cupa N, Christ-Crain M. Comparison of 1 mg versus 2 mg Dexamethasone Suppression Test in Patients with Obesity. Horm Metab Res. 2017 Nov;49(11):854-859. doi: 10.1055/s-0043-119128. Epub 2017 Sep 29.
PubMed 28962047Urwyler SA, Schuetz P, Ebrahimi F, Donath MY, Christ-Crain M. Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals. J Clin Endocrinol Metab. 2017 May 1;102(5):1712-1718. doi: 10.1210/jc.2016-3931.
PubMed 28324042
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of IL-1 Beta on the Hypothalamic-pituitary-adrenal (HPA) Axis in Obese Persons - the CortIL-Study
- ClinicalTrials.gov ID
- NCT02227420
- Acronym / sponsor ID
- CortIL / EKNZ 2014-175
- Conditions
- Metabolic Syndrome, Hypersecretion; Cortisol
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Mar 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 28 Aug 2014 (estimated)
- 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 obese individuals cortisol production and secretion is increased but the underlying mechanism is not known. Obesity leads to a pathological activation of the innate immune system partly driven by tissue production of IL-1β. Furthermore, IL-1β is also known to stimulate the release of adrenocorticotropin hormone (ACTH). Therefore, the investigators hypothesise that in obese individuals tissue inflammation stimulates ACTH via IL-1β, thereby explaining the observed hypercortisolism.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anakinra | Experimental | Drug: AnakinraAnakinra 100mg s.c. x 5 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18-80 years
- BMI >30kg/m2 and at least 1 manifestations of the metabolic syndrome (i.e. diabetes/ prediabetes, hypertension, dyslipidemia)
- Willingness to use contraceptive measures adequate to prevent becoming pregnant
Key exclusion criteria (12 listed)
- Medication with glucocorticosteroids
- Known Cushing Syndrome
- Pregnancy or breast feeding
- Clinical signs of infection in the week before inclusion or history of a severe infection during the last 2 months
- Hematologic disease (leukocyte count < 1.5x109/l, hemoglobin <11 g/dl, platelets <100 x 103/ul)
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 |
|---|---|---|
| AnakinraAnakinra 100mg s.c. x 5 | Drug | Anakinra |
Primary outcome
Morning cortisol levels
Time frame: 14 days
5 secondary outcomes
effect of anakinra/Kineret® on salivary cortisol, free urinary cortisol, and serum cortisol levels after an overnight dexamethasone suppression test
Time frame: 14 days
correlation between the percentage of body fat or body mass index, and suppression of cortisol levels after injection of anakinra/Kineret®
Time frame: 14 days
correlation between inflammatory parameters with cortisol levels
Time frame: 14 days
impact of anakinra/Kineret® on other pituitary and peripheral hormones, such as: ACTH, TSH, fT4, GH, IGF-1, LH, FSH, testosterone copeptin, IL-6, CRP, leukocyte count and body temperature.
Time frame: 14 days
comparison of 1mg and 2mg dexamethasone suppression test
Time frame: 4 weeks
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 2016.
- Derived from this study: PubMed 32275191Urwyler SA, Ebrahimi F, Burkard T, Schuetz P, Poglitsch M, Mueller B, Donath MY, Christ-Crain M. IL (Interleukin)-1 Receptor Antagonist Increases Ang (Angiotensin [1-7]) and Decreases Blood Pressure in Obese Individuals. Hypertension. 2020 Jun;75(6):1455-1463. doi: 10.1161/HYPERTENSIONAHA.119.13982. Epub 2020 Apr 10.
- Derived from this study: PubMed 28962047Urwyler SA, Cupa N, Christ-Crain M. Comparison of 1 mg versus 2 mg Dexamethasone Suppression Test in Patients with Obesity. Horm Metab Res. 2017 Nov;49(11):854-859. doi: 10.1055/s-0043-119128. Epub 2017 Sep 29.
- Derived from this study: PubMed 28324042Urwyler SA, Schuetz P, Ebrahimi F, Donath MY, Christ-Crain M. Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals. J Clin Endocrinol Metab. 2017 May 1;102(5):1712-1718. doi: 10.1210/jc.2016-3931.
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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.
Mirjam Christ-Crain, MD, Prof. principal investigator
University Hospital, Basel, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Anakinra in people with Metabolic Syndrome and Hypersecretion; Cortisol, run by University Hospital, Basel, Switzerland 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 3 inclusion and 12 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 2016. 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. 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?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Morning cortisol levels (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02227420, which also lists 3 linked publications.
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 2016.