<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/NCT01688349</url>
  </required_header>
  <id_info>
    <org_study_id>P110906</org_study_id>
    <secondary_id>CRC11001</secondary_id>
    <nct_id>NCT01688349</nct_id>
  </id_info>
  <brief_title>Pattern of Gene Expression in Adipose Tissue From Patients With Cushing Syndrome</brief_title>
  <acronym>LIPOCUSH</acronym>
  <official_title>Comparative Study of Subcutaneous and Visceral Adipose Tissue in Patients Affected by Cushing Syndrome Versus 2 Controls Population</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this trial is to investigate the impact of cortisol on adipose tissue&#xD;
      functions, distribution and morphology. Patient with endogenous blood cortisol excess exhibit&#xD;
      changes in adipose tissue, with fat gain in the upper trunk, face and neck leading to&#xD;
      visceral obesity and features of the metabolic syndrome. The aims of this study will be&#xD;
&#xD;
        -  to compare the pattern of gene expression between visceral and subcutaneous adipose&#xD;
           tissue in Cushing patients requiring an adrenalectomy as cortisol adenoma treatment;&#xD;
&#xD;
        -  to compare these patterns of gene expression with those of two control populations:1/&#xD;
           healthy metabolic subjects having a partial nephrectomy, 2/obese patients with similar&#xD;
           degree of insulin resistance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cushing's syndrome is a rare disease resulting from chronic exposure to glucocorticoids&#xD;
      (endogenous or iatrogenic) with abnormal fat distribution (lipodystrophy). Glucocorticoids&#xD;
      regulate the functions of adipose tissue (AT) targeting adipocyte differentiation as well as&#xD;
      anabolic, catabolic and secretory pathways of the adipocyte. However, the mechanisms by which&#xD;
      glucocorticoids differentially disrupt the development or metabolism of AT between deep and&#xD;
      superficial deposits remain unknown. Among the main effectors of the glucocorticoid signaling&#xD;
      pathway, 11 beta-hydroxysteroid deshydrogenase (11beta-HSD1) , that regenerate cortisol from&#xD;
      cortisone, is likely a key step in the biological effect of glucocorticoids in AT.&#xD;
      Identifying these mechanisms of action of glucocorticoids on different fat depots requires&#xD;
      the comparison with fatty deposits derived from two types of control populations: 1/ normal&#xD;
      weight individuals without inflammatory or metabolic disorder (controls1); 2/individuals&#xD;
      obese matched for the level of insulin resistance (controls2).&#xD;
&#xD;
      Hypothesis: Excess glucocorticoids cause abnormal fat distribution via a direct effect on the&#xD;
      various deposits of AT, leading secondarily to insulin resistance.&#xD;
&#xD;
      Primary endpoint: To compare gene expression of glucocorticoid signaling between the visceral&#xD;
      AT (VAT) of Cushing patients with that of controls1 (matched for age and sex).&#xD;
&#xD;
      Secondary endpoints:&#xD;
&#xD;
        1. For patients with Cushing and controls1, to compare their respective subcutaneous AT&#xD;
           (SCAT) and VAT for:&#xD;
&#xD;
             -  The expression of genes involved in differentiation and inflammation of the AT,&#xD;
&#xD;
             -  Morphological aspects: adipocyte size, fibrosis, inflammation,&#xD;
                immunohistochemistry.&#xD;
&#xD;
        2. Same parameters for Cushing patients and controls2 (matched for sex, age + / -5, HOMA-R&#xD;
           + / -1), to differentiate the specific effects of glucocorticoid from the effects of&#xD;
           insulin resistance,&#xD;
&#xD;
        3. To compare these parameters between SCAT and VAT from Cushing patients. Methodology and&#xD;
           experimental design: non-randomized comparative multicenter study with constitution of a&#xD;
           biological collection.&#xD;
&#xD;
      Patients will be recruited in endocrinology before adrenalectomy and controls1 in urology.&#xD;
      They will have a preoperative assessment and sampling of perirenal AT and SCAT at surgery.&#xD;
      Controls2 are already included in the CRC2007-P050318 and will be drawn for matching.&#xD;
&#xD;
      Number of patients needed: We assume the relative gene expression of 11β-HSD1 in the VAT not&#xD;
      exposed to glucocorticoids = 0.81 ± 0.121. Our recruitment potential of Cushing patients is&#xD;
      30 patients. With 30 patients per group, we will be able to detect a difference in 11β-HSD1&#xD;
      gene expression in the VAT of Cushing patients at least 15% higher compared to controls1.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">September 16, 2016</completion_date>
  <primary_completion_date type="Actual">September 16, 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison between visceral adipose tissue of Cushing patients and that of normal weight controls.</measure>
    <time_frame>1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)</time_frame>
    <description>Comparison of glucocorticoid pathway genes expression between visceral adipose tissue of Cushing patients and that of normal weight controls matched on sex and age.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of the respective SCAT and VAT between Cushing patients and normal weight controls.</measure>
    <time_frame>1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)</time_frame>
    <description>For patients with Cushing and controls1, to compare their respective SCAT and VAT for:&#xD;
The expression of genes involved in differentiation and inflammation of the AT,&#xD;
Morphological aspects: adipocyte size, fibrosis, inflammation, immunohistochemistry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the respective SCAT and VAT between Cushing patients and obese controls.</measure>
    <time_frame>1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)</time_frame>
    <description>Comparison of these same parameters(secondary outcome n°1) between Cushing patients and controls2 (matched for sex, age + / -5, HOMA-R + / -1), to differentiate the specific effects of glucocorticoid from the effects of insulin resistance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>comparison between SCAT and VAT from Cushing patients</measure>
    <time_frame>1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)</time_frame>
    <description>To compare these parameters between SCAT and VAT from Cushing patients</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Cushing Syndrome Related to Cortisolic Adenoma</condition>
  <arm_group>
    <arm_group_label>Cushing group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AT biopsy during partial nephrectomy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls1</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>normal weight metabolic healthy patients having partial nephrectomy with small AT Biopsy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls2</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>obese individuals already included and having biopsies of VAT and SCAT stocked.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>analyze the role of glucocorticoid in AT distribution.</intervention_name>
    <description>The purpose of this trial is to investigate the impact of cortisol on adipose tissue functions, distribution and morphology. Patient with endogenous blood cortisol excess exhibit changes in adipose tissue, with fat gain in the upper trunk, face and neck leading to visceral obesity and features of the metabolic syndrome. The aims of this study will be&#xD;
to compare the pattern of gene expression between visceral and subcutaneous adipose tissue in Cushing patients requiring an adrenalectomy as cortisol adenoma treatment;&#xD;
to compare these patterns of gene expression with those of two control populations:1/ healthy metabolic subjects having a partial nephrectomy, 2/obese patients with similar degree of insulin resistance.</description>
    <arm_group_label>Controls1</arm_group_label>
    <arm_group_label>Controls2</arm_group_label>
    <arm_group_label>Cushing group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cases: Adults with Cushing's syndrome secondary to adrenal adenoma.&#xD;
&#xD;
          -  Controls1: Adults with normal weight: BMI &lt;25, having partial nephrectomy&#xD;
&#xD;
          -  Controls2 adults with common obesity treated by bariatric surgery, BMI&gt; 35kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diabetes, renal or hepatic impairment, pregnancy, menopause, HIV or HCV, Cushing's&#xD;
             syndrome due to other causes than cortisol adenoma&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruno Feve, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Saint-Antoine, service d'Endocrinologie</name>
      <address>
        <city>Paris</city>
        <zip>75012</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>August 2, 2012</study_first_submitted>
  <study_first_submitted_qc>September 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2012</study_first_posted>
  <last_update_submitted>March 21, 2017</last_update_submitted>
  <last_update_submitted_qc>March 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glucocorticoids</keyword>
  <keyword>adipose tissue</keyword>
  <keyword>Cushing</keyword>
  <keyword>lipodystrophy</keyword>
  <keyword>11 beta-HSD1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenoma</mesh_term>
    <mesh_term>Cushing Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glucocorticoids</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/NCT01688349
org study id: P110906
secondary id: CRC11001
nct id: NCT01688349
lead sponsor: 
has dmc: No
The purpose of this trial is to investigate the impact of cortisol on adipose tissue
      functions, distribution and morphology. Patient with endogenous blood cortisol excess exhibit
      changes in adipose tissue, with fat gain in the upper trunk, face and neck leading to
      visceral obesity and features of the metabolic syndrome. The aims of this study will be

        -  to compare the pattern of gene expression between visceral and subcutaneous adipose
           tissue in Cushing patients requiring an adrenalectomy as cortisol adenoma treatment;

        -  to compare these patterns of gene expression with those of two control populations:1/
           healthy metabolic subjects having a partial nephrectomy, 2/obese patients with similar
           degree of insulin resistance.
Cushing's syndrome is a rare disease resulting from chronic exposure to glucocorticoids
      (endogenous or iatrogenic) with abnormal fat distribution (lipodystrophy). Glucocorticoids
      regulate the functions of adipose tissue (AT) targeting adipocyte differentiation as well as
      anabolic, catabolic and secretory pathways of the adipocyte. However, the mechanisms by which
      glucocorticoids differentially disrupt the development or metabolism of AT between deep and
      superficial deposits remain unknown. Among the main effectors of the glucocorticoid signaling
      pathway, 11 beta-hydroxysteroid deshydrogenase (11beta-HSD1) , that regenerate cortisol from
      cortisone, is likely a key step in the biological effect of glucocorticoids in AT.
      Identifying these mechanisms of action of glucocorticoids on different fat depots requires
      the comparison with fatty deposits derived from two types of control populations: 1/ normal
      weight individuals without inflammatory or metabolic disorder (controls1); 2/individuals
      obese matched for the level of insulin resistance (controls2).

      Hypothesis: Excess glucocorticoids cause abnormal fat distribution via a direct effect on the
      various deposits of AT, leading secondarily to insulin resistance.

      Primary endpoint: To compare gene expression of glucocorticoid signaling between the visceral
      AT (VAT) of Cushing patients with that of controls1 (matched for age and sex).

      Secondary endpoints:

        1. For patients with Cushing and controls1, to compare their respective subcutaneous AT
           (SCAT) and VAT for:

             -  The expression of genes involved in differentiation and inflammation of the AT,

             -  Morphological aspects: adipocyte size, fibrosis, inflammation,
                immunohistochemistry.

        2. Same parameters for Cushing patients and controls2 (matched for sex, age + / -5, HOMA-R
           + / -1), to differentiate the specific effects of glucocorticoid from the effects of
           insulin resistance,

        3. To compare these parameters between SCAT and VAT from Cushing patients. Methodology and
           experimental design: non-randomized comparative multicenter study with constitution of a
           biological collection.

      Patients will be recruited in endocrinology before adrenalectomy and controls1 in urology.
      They will have a preoperative assessment and sampling of perirenal AT and SCAT at surgery.
      Controls2 are already included in the CRC2007-P050318 and will be drawn for matching.

      Number of patients needed: We assume the relative gene expression of 11β-HSD1 in the VAT not
      exposed to glucocorticoids = 0.81 ± 0.121. Our recruitment potential of Cushing patients is
      30 patients. With 30 patients per group, we will be able to detect a difference in 11β-HSD1
      gene expression in the VAT of Cushing patients at least 15% higher compared to controls1.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Outcomes Assessor)
measure: Comparison between visceral adipose tissue of Cushing patients and that of normal weight controls.
time frame: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
description: Comparison of glucocorticoid pathway genes expression between visceral adipose tissue of Cushing patients and that of normal weight controls matched on sex and age.
measure: Comparison of the respective SCAT and VAT between Cushing patients and normal weight controls.
time frame: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
description: For patients with Cushing and controls1, to compare their respective SCAT and VAT for:
The expression of genes involved in differentiation and inflammation of the AT,
Morphological aspects: adipocyte size, fibrosis, inflammation, immunohistochemistry.
measure: Comparison of the respective SCAT and VAT between Cushing patients and obese controls.
time frame: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
description: Comparison of these same parameters(secondary outcome n°1) between Cushing patients and controls2 (matched for sex, age + / -5, HOMA-R + / -1), to differentiate the specific effects of glucocorticoid from the effects of insulin resistance
measure: comparison between SCAT and VAT from Cushing patients
time frame: 1 day (gene expression will be tested on AT withdraw the day of surgical adrenalectomy)
description: To compare these parameters between SCAT and VAT from Cushing patients
arm group label: Cushing group
arm group type: Experimental
description: AT biopsy during partial nephrectomy
arm group label: Controls1
arm group type: Other
description: normal weight metabolic healthy patients having partial nephrectomy with small AT Biopsy.
arm group label: Controls2
arm group type: Other
description: obese individuals already included and having biopsies of VAT and SCAT stocked.
intervention type: Other
intervention name: analyze the role of glucocorticoid in AT distribution.
description: The purpose of this trial is to investigate the impact of cortisol on adipose tissue functions, distribution and morphology. Patient with endogenous blood cortisol excess exhibit changes in adipose tissue, with fat gain in the upper trunk, face and neck leading to visceral obesity and features of the metabolic syndrome. The aims of this study will be
to compare the pattern of gene expression between visceral and subcutaneous adipose tissue in Cushing patients requiring an adrenalectomy as cortisol adenoma treatment;
to compare these patterns of gene expression with those of two control populations:1/ healthy metabolic subjects having a partial nephrectomy, 2/obese patients with similar degree of insulin resistance.
arm group label: Controls1
arm group label: Controls2
arm group label: Cushing group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bruno Feve, PhD
role: Principal Investigator
affiliation: Assistance Publique
facility: 
country: France
responsible party type: Sponsor
mesh term: Adenoma
mesh term: Cushing Syndrome
mesh term: Syndrome
mesh term: Glucocorticoids