Effects of IL-1 Beta on the HPA-axis in Obese Persons

Study Overview
=================
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.

Official Title
-----------------
Effects of IL-1 Beta on the Hypothalamic-pituitary-adrenal (HPA) Axis in Obese Persons - the CortIL-Study

Conditions
-----------------
Metabolic Syndrome, Hypersecretion; Cortisol

Intervention / Treatment
-----------------
* Drug: Anakinra


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anakinra<br>Anakinra 100mg s.c. x 5 | Drug: Anakinra<br>* Anakinra 100mg s.c. x 5<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morning cortisol levels |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect of anakinra/Kineret® on salivary cortisol, free urinary cortisol, and serum cortisol levels after an overnight dexamethasone suppression test |  | 14 days | 
| correlation between the percentage of body fat or body mass index, and suppression of cortisol levels after injection of anakinra/Kineret® |  | 14 days | 
| correlation between inflammatory parameters with cortisol levels |  | 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. | 14 days | 
| comparison of 1mg and 2mg dexamethasone suppression test |  | 4 weeks |