Clinical trial NCT02227420: Effects of IL-1 Beta on the HPA-axis in Obese Persons
Official title: Effects of IL-1 Beta on the Hypothalamic-pituitary-adrenal (HPA) Axis in Obese Persons - the CortIL-Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metabolic Syndrome
Hypersecretion; Cortisol
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2014-08-28
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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))
* 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

Primary outcomes:
measure: Morning cortisol levels
timeFrame: 14 days
Secondary outcomes:
measure: effect of anakinra/Kineret® on salivary cortisol, free urinary cortisol, and serum cortisol levels after an overnight dexamethasone suppression test
timeFrame: 14 days
measure: correlation between the percentage of body fat or body mass index, and suppression of cortisol levels after injection of anakinra/Kineret®
timeFrame: 14 days
measure: correlation between inflammatory parameters with cortisol levels
timeFrame: 14 days
measure: 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.
timeFrame: 14 days
measure: comparison of 1mg and 2mg dexamethasone suppression test
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hopsital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Mirjam Christ-Crain, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Urwyler 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.
citation: Urwyler 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.