<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02227420</url>
  </required_header>
  <id_info>
    <org_study_id>EKNZ 2014-175</org_study_id>
    <nct_id>NCT02227420</nct_id>
  </id_info>
  <brief_title>Effects of IL-1 Beta on the HPA-axis in Obese Persons</brief_title>
  <acronym>CortIL</acronym>
  <official_title>Effects of IL-1 Beta on the Hypothalamic-pituitary-adrenal (HPA) Axis in Obese Persons - the CortIL-Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In obese individuals cortisol production and secretion is increased but the underlying&#xD;
      mechanism is not known. Obesity leads to a pathological activation of the innate immune&#xD;
      system partly driven by tissue production of IL-1β. Furthermore, IL-1β is also known to&#xD;
      stimulate the release of adrenocorticotropin hormone (ACTH). Therefore, the investigators&#xD;
      hypothesise that in obese individuals tissue inflammation stimulates ACTH via IL-1β, thereby&#xD;
      explaining the observed hypercortisolism.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Morning cortisol levels</measure>
    <time_frame>14 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>effect of anakinra/Kineret® on salivary cortisol, free urinary cortisol, and serum cortisol levels after an overnight dexamethasone suppression test</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>correlation between the percentage of body fat or body mass index, and suppression of cortisol levels after injection of anakinra/Kineret®</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>correlation between inflammatory parameters with cortisol levels</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <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.</measure>
    <time_frame>14 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>comparison of 1mg and 2mg dexamethasone suppression test</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">76</enrollment>
  <condition>Metabolic Syndrome</condition>
  <condition>Hypersecretion; Cortisol</condition>
  <arm_group>
    <arm_group_label>Anakinra</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anakinra 100mg s.c. x 5</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anakinra</intervention_name>
    <description>Anakinra 100mg s.c. x 5</description>
    <arm_group_label>Anakinra</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-80 years&#xD;
&#xD;
          -  BMI &gt;30kg/m2 and at least 1 manifestations of the metabolic syndrome (i.e. diabetes/&#xD;
             prediabetes, hypertension, dyslipidemia)&#xD;
&#xD;
          -  Willingness to use contraceptive measures adequate to prevent becoming pregnant&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medication with glucocorticosteroids&#xD;
&#xD;
          -  Known Cushing Syndrome&#xD;
&#xD;
          -  Pregnancy or breast feeding&#xD;
&#xD;
          -  Clinical signs of infection in the week before inclusion or history of a severe&#xD;
             infection during the last 2 months&#xD;
&#xD;
          -  Hematologic disease (leukocyte count &lt; 1.5x109/l, hemoglobin &lt;11 g/dl, platelets &lt;100&#xD;
             x 103/ul)&#xD;
&#xD;
          -  Kidney disease (creatinine-clearance &lt; 30ml/min))&#xD;
&#xD;
          -  Liver disease (transaminases &gt;4x upper normal range)&#xD;
&#xD;
          -  Active carcinoma&#xD;
&#xD;
          -  History of tuberculosis&#xD;
&#xD;
          -  Alcohol consumption &gt;40g/d for men, &gt;30g/d for women&#xD;
&#xD;
          -  Known allergy towards anakinra&#xD;
&#xD;
          -  Subject refusing or unable to give written informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mirjam Christ-Crain, MD, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Basel, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hopsital Basel</name>
      <address>
        <city>Basel</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <last_update_submitted>August 22, 2016</last_update_submitted>
  <last_update_submitted_qc>August 22, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 23, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interleukin 1 Receptor Antagonist Protein</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02227420
org study id: EKNZ 2014-175
nct id: NCT02227420
lead sponsor: 
has dmc: Yes
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.
allocation: N/A
intervention model: Single Group Assignment
masking: None (Open Label)
measure: Morning cortisol levels
time frame: 14 days
measure: effect of anakinra/Kineret® on salivary cortisol, free urinary cortisol, and serum cortisol levels after an overnight dexamethasone suppression test
time frame: 14 days
measure: 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
measure: correlation between inflammatory parameters with cortisol levels
time frame: 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.
time frame: 14 days
description: 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.
measure: comparison of 1mg and 2mg dexamethasone suppression test
time frame: 4 weeks
arm group label: Anakinra
arm group type: Experimental
description: Anakinra 100mg s.c. x 5
intervention type: Drug
intervention name: Anakinra
description: Anakinra 100mg s.c. x 5
arm group label: Anakinra
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Mirjam Christ-Crain, MD, Prof.
role: Principal Investigator
affiliation: University Hospital, Basel, Switzerland
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Metabolic Syndrome
mesh term: Interleukin 1 Receptor Antagonist Protein