<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/NCT03817840</url>
  </required_header>
  <id_info>
    <org_study_id>AAAR7901</org_study_id>
    <nct_id>NCT03817840</nct_id>
  </id_info>
  <brief_title>Novel Mediators of the Lipodystrophy and Metabolic Consequences of Cushing's Disease</brief_title>
  <official_title>Novel Mediators of the Lipodystrophy and Metabolic Consequences of Cushing's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>New York Obesity and Nutrition Research Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This proposal will evaluate the glucocorticoid mediated changes in body fat distribution and&#xD;
      metabolism that occur in patients with Cushing's disease. The objective is to identify the&#xD;
      mechanisms that influence both the accumulation of lipodystrophic fat and also the changes in&#xD;
      energy expenditure and metabolism that accompany them. The study is designed to determine if&#xD;
      the high cortisol and AgRP levels in the blood of people living with Cushing's syndrome,&#xD;
      either from taking steroid medications or from tumors, impact body fat and metabolism by&#xD;
      turning off brown fat, which is a type of fat that increases one's metabolism.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cushing's disease (CD) is a disorder of chronic glucocorticoid (GC) excess that gives rise to&#xD;
      a constellation of metabolic comorbidities and to a distinct lipodystrophic body habitus&#xD;
      characterized by central adiposity, extremity wasting, and the accumulation of&#xD;
      supraclavicular (SC) and dorsocervical (DC) fat in the region where human brown and beige&#xD;
      adipose tissue is known to be concentrated. In spite of the recognized thermogenic capacity&#xD;
      of select cervical adipocytes, the potential impact of lipomatous alterations in this depot&#xD;
      on energy balance and metabolism in CD is unknown. To our knowledge, the &quot;buffalo hump&quot; and&#xD;
      the supraclavicular fat pads - which are a sensitive physical finding for CD, have never been&#xD;
      phenotypically characterized and the mechanisms underlying the GC mediated development of fat&#xD;
      in these depots and the associated metabolic complications have not been explored in humans.&#xD;
      The proposed research will advance our understanding of Cushing's lipodystrophy and its&#xD;
      metabolic complications. Furthermore, it may lead to the identification of novel mediators&#xD;
      and targetable pathways to attenuate the adverse effects of hypercortisolism on body&#xD;
      composition and metabolism in CD, as well as in the significant population of patients&#xD;
      treated with chronic GCs for an array of other clinical conditions. These findings may have&#xD;
      important implications not only for those with Cushing's disease, but for the millions of&#xD;
      Americans who are treated with chronic glucocorticoids for an array of clinical conditions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 16, 2018</start_date>
  <completion_date type="Actual">July 1, 2021</completion_date>
  <primary_completion_date type="Actual">July 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Energy Expenditure</measure>
    <time_frame>Change from baseline REE at 3 months post-treatment</time_frame>
    <description>Resting energy expenditure (REE) will be measured by whole room indirect calorimetry prior to and following cure of Cushing's Disease (CD).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total body adipose tissue volume</measure>
    <time_frame>Change in total body adipose tissue volume from baseline at 3 months post-treatment</time_frame>
    <description>Whole body MRI will be utilized to measure total body adipose tissue volume</description>
  </secondary_outcome>
  <enrollment type="Actual">8</enrollment>
  <condition>Cushing's Syndrome</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Treatment of Cushing's</intervention_name>
    <description>Surgical resection of ACTH-secreting tumor to achieve cure of hypercortisolism</description>
    <other_name>Medical treatment of hypercortisolism</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Subjects will undergo 4mm punch biopsies of the SC, DC, and subcutaneous abdominal fat pads&#xD;
      under local anesthesia (lidocaine). Biopsies will be performed by an interventional&#xD;
      radiologist or surgeon. Specimens will be prepared for histologic analysis and for&#xD;
      immunohistochemical analysis for brown and white adipose tissue markers.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with ACTH-dependent Cushing's syndrome&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged 18-70 yrs&#xD;
&#xD;
          2. Body mass index (BMI) &lt;35 kg/m2&#xD;
&#xD;
          3. Urine free cortisol (UFC) ≥150ug/d&#xD;
&#xD;
          4. Pituitary tumor &gt;6mm on MRI or an inferior petrosal sinus sampling with central to&#xD;
             peripheral plasma adrenocorticotropic hormone (ACTH) gradient&#xD;
&#xD;
          5. Normal renal and thyroid function&#xD;
&#xD;
          6. HbA1c ≤8.0.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Smoking&#xD;
&#xD;
          2. Alcohol &gt;2 drinks/day&#xD;
&#xD;
          3. Uncontrolled hypertension&#xD;
&#xD;
          4. HIV given potential for lipodystrophic confounding&#xD;
&#xD;
          5. Pregnancy and nursing&#xD;
&#xD;
          6. Use of beta-blockers, β-adrenergic or diabetes medications other than insulin&#xD;
&#xD;
          7. History of claustrophobia or difficulty lying flat&#xD;
&#xD;
          8. In-dwelling metal hardware.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gabrielle Page-Wilson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Neuroendocrine Unit</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>July 12, 2021</last_update_submitted>
  <last_update_submitted_qc>July 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Gabrielle Page-Wilson</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Glucocorticoids</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>ACTH-Secreting Pituitary Adenoma</mesh_term>
    <mesh_term>Pituitary ACTH Hypersecretion</mesh_term>
    <mesh_term>Lipodystrophy</mesh_term>
    <mesh_term>Cushing Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03817840
org study id: AAAR7901
nct id: NCT03817840
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This proposal will evaluate the glucocorticoid mediated changes in body fat distribution and
      metabolism that occur in patients with Cushing's disease. The objective is to identify the
      mechanisms that influence both the accumulation of lipodystrophic fat and also the changes in
      energy expenditure and metabolism that accompany them. The study is designed to determine if
      the high cortisol and AgRP levels in the blood of people living with Cushing's syndrome,
      either from taking steroid medications or from tumors, impact body fat and metabolism by
      turning off brown fat, which is a type of fat that increases one's metabolism.
Cushing's disease (CD) is a disorder of chronic glucocorticoid (GC) excess that gives rise to
      a constellation of metabolic comorbidities and to a distinct lipodystrophic body habitus
      characterized by central adiposity, extremity wasting, and the accumulation of
      supraclavicular (SC) and dorsocervical (DC) fat in the region where human brown and beige
      adipose tissue is known to be concentrated. In spite of the recognized thermogenic capacity
      of select cervical adipocytes, the potential impact of lipomatous alterations in this depot
      on energy balance and metabolism in CD is unknown. To our knowledge, the "buffalo hump" and
      the supraclavicular fat pads - which are a sensitive physical finding for CD, have never been
      phenotypically characterized and the mechanisms underlying the GC mediated development of fat
      in these depots and the associated metabolic complications have not been explored in humans.
      The proposed research will advance our understanding of Cushing's lipodystrophy and its
      metabolic complications. Furthermore, it may lead to the identification of novel mediators
      and targetable pathways to attenuate the adverse effects of hypercortisolism on body
      composition and metabolism in CD, as well as in the significant population of patients
      treated with chronic GCs for an array of other clinical conditions. These findings may have
      important implications not only for those with Cushing's disease, but for the millions of
      Americans who are treated with chronic glucocorticoids for an array of clinical conditions.
observational model: Cohort
time perspective: Prospective
measure: Energy Expenditure
time frame: Change from baseline REE at 3 months post-treatment
description: Resting energy expenditure (REE) will be measured by whole room indirect calorimetry prior to and following cure of Cushing's Disease (CD).
measure: Total body adipose tissue volume
time frame: Change in total body adipose tissue volume from baseline at 3 months post-treatment
description: Whole body MRI will be utilized to measure total body adipose tissue volume
intervention type: Procedure
intervention name: Treatment of Cushing's
description: Surgical resection of ACTH-secreting tumor to achieve cure of hypercortisolism
other name: Medical treatment of hypercortisolism
Subjects will undergo 4mm punch biopsies of the SC, DC, and subcutaneous abdominal fat pads
      under local anesthesia (lidocaine). Biopsies will be performed by an interventional
      radiologist or surgeon. Specimens will be prepared for histologic analysis and for
      immunohistochemical analysis for brown and white adipose tissue markers.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Gabrielle Page-Wilson, MD
role: Principal Investigator
affiliation: Columbia University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Columbia University
investigator full name: Gabrielle Page-Wilson
investigator title: Assistant Professor of Medicine
mesh term: ACTH-Secreting Pituitary Adenoma
mesh term: Pituitary ACTH Hypersecretion
mesh term: Lipodystrophy
mesh term: Cushing Syndrome
sharing ipd: No