NCT02227420

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
76

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Oct 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 26, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 28, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

October 1, 2014

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2016

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2016

Completed
Last Updated

August 23, 2016

Status Verified

August 1, 2016

Enrollment Period

1.4 years

First QC Date

August 26, 2014

Last Update Submit

August 22, 2016

Conditions

Metabolic SyndromeHypersecretion; Cortisol

Outcome Measures

Primary Outcomes (1)

  • Morning cortisol levels

    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

    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.

    14 days

  • comparison of 1mg and 2mg dexamethasone suppression test

    4 weeks

Study Arms (1)

Anakinra

EXPERIMENTAL

Anakinra 100mg s.c. x 5

Drug: Anakinra

Interventions

AnakinraDRUG

Anakinra 100mg s.c. x 5

Anakinra

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Medication with glucocorticosteroids
  • Known Cushing Syndrome
  • Pregnancy or breast feeding
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hopsital Basel

Basel, Switzerland

Location

Related Publications (3)

  • 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.

    PMID: 32275191DERIVED

  • 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.

    PMID: 28962047DERIVED

  • 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.

    PMID: 28324042DERIVED

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Insulin ResistanceHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

CytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Study Officials

  • Mirjam Christ-Crain, MD, Prof.

    University Hospital, Basel, Switzerland

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NA
Masking
NONE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 26, 2014

First Posted

August 28, 2014

Study Start

October 1, 2014

Primary Completion

March 1, 2016

Study Completion

July 1, 2016

Last Updated

August 23, 2016

Record last verified: 2016-08

Locations

CH(1)