<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/NCT01671605</url>
  </required_header>
  <id_info>
    <org_study_id>090846</org_study_id>
    <nct_id>NCT01671605</nct_id>
  </id_info>
  <brief_title>Mechanisms of Chronic Kidney Disease (CKD)-Induced Foam Cell Formation</brief_title>
  <official_title>Mechanisms of CKD-Induced Foam Cell Formation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      There is currently little understanding of macrophage cholesterol homeostasis and foam cell&#xD;
      formation across the spectrum of CKD. We hypothesize that an inverse relationship exist&#xD;
      between the severity of CKD and processes underlying foam cell formation, and that the&#xD;
      relationship becomes independent of serum lipoprotein levels as renal function declines. We&#xD;
      propose to systematically examine scavenger receptors and cholesterol uptake as well as&#xD;
      cholesterol transporters and efflux mechanisms in individuals with normal renal function,&#xD;
      patients with moderate CKD. We further propose to determine if processed contributing to foam&#xD;
      cell formation are related to the plasma lipid profile and if the relationship is modified by&#xD;
      co-morbidities, such as diabetes, obesity, systemic inflammation which are common in this&#xD;
      population and directly influence vascular integrity. These data will be critically important&#xD;
      to understand when the abnormality starts and will provide crucial information.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>In Vitro Lipoprotein Functions</measure>
    <time_frame>Once, at enrollment</time_frame>
    <description>Cholesterol efflux. Baseline and outcome measurements are the same. The cholesterol efflux was measured once using HDL isolated from CKD and control patients. There was no intervention,this assessment was performed once in each group. The measurement of cholesterol efflux is performed by an in vitro assay in cultured cells. Cells are loaded with cholesterol and maintained for 72 hours. The media of the cultured cells is then changed and the new media contains HDL from CKD or control patients. In additional cells, no HDL is added. The cells are maintained for 24 hours, and intracellular cholesterol is assessed. The cholesterol efflux represents the amount of cholesterol that was leached by HDL from each of our study groups. Thus, cells not exposed to any HDL will contain the highest intracellular cholesterol content. The amount of cholesterol in cells exposed to CKD HDL or control HDL reflects the efflux capacity of that HDL. This is expressed as percent of cholesterol removed by HDL.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">103</enrollment>
  <condition>Chronic Kidney Disease</condition>
  <condition>Cardiovascular Disease</condition>
  <arm_group>
    <arm_group_label>CKD not on dialysis</arm_group_label>
    <description>Patients with CKD not on dialysis (CKD III-IV)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Controls with normal kidney function (Control)</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with CKD not on dialysis (CKD III-IV)&#xD;
&#xD;
        Controls with normal kidney function (Control)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients with moderate degree of CKD, or patients with advanced CKD or control subjects&#xD;
        with intact kidney function&#xD;
&#xD;
        Male or female&#xD;
&#xD;
        All ethnic groups&#xD;
&#xD;
        ≥ 18 years and have signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Pregnancy and current smoking&#xD;
&#xD;
        BMI &gt; 45&#xD;
&#xD;
        Rheumatoid arthritis and systemic lupus erythematosus&#xD;
&#xD;
        History of active or chronic hepatitis B, history of active or chronic hepatitis C, human&#xD;
        immunodeficiency virus (HIV)&#xD;
&#xD;
        For moderate CKD subjects: nephrotic syndrome&#xD;
&#xD;
        For control subjects: nephrotic syndrome, patients with estimated GFR &lt; 60 mL/min/1.73 m^2,&#xD;
        or proteinuria&#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>Valentina Kon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt Outpatient Dialysis Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>August 20, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 23, 2012</study_first_posted>
  <results_first_submitted>November 22, 2016</results_first_submitted>
  <results_first_submitted_qc>March 10, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 21, 2017</results_first_posted>
  <last_update_submitted>March 10, 2017</last_update_submitted>
  <last_update_submitted_qc>March 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University</investigator_affiliation>
    <investigator_full_name>Valentina Kon</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>CKD Not on Dialysis</title>
          <description>Patients with CKD not on dialysis (CKD III-IV)</description>
        </group>
        <group group_id="P2">
          <title>Controls</title>
          <description>Controls with normal kidney function (Control)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="72"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="72"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>With or without Chronic Kidney Disease</population>
      <group_list>
        <group group_id="B1">
          <title>CKD Not on Dialysis</title>
          <description>Patients with CKD not on dialysis (CKD III-IV)</description>
        </group>
        <group group_id="B2">
          <title>Controls</title>
          <description>Controls with normal kidney function (Control)</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="72"/>
            <count group_id="B2" value="31"/>
            <count group_id="B3" value="103"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.9" spread="13.5"/>
                    <measurement group_id="B2" value="49.9" spread="10.6"/>
                    <measurement group_id="B3" value="55.9" spread="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="85"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="72"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HDL Function</title>
          <units>Percentage</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20.8" lower_limit="16.1" upper_limit="23.7"/>
                    <measurement group_id="B2" value="26.5" lower_limit="19.6" upper_limit="28.5"/>
                    <measurement group_id="B3" value="23.65" lower_limit="16.1" upper_limit="28.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>In Vitro Lipoprotein Functions</title>
        <description>Cholesterol efflux. Baseline and outcome measurements are the same. The cholesterol efflux was measured once using HDL isolated from CKD and control patients. There was no intervention,this assessment was performed once in each group. The measurement of cholesterol efflux is performed by an in vitro assay in cultured cells. Cells are loaded with cholesterol and maintained for 72 hours. The media of the cultured cells is then changed and the new media contains HDL from CKD or control patients. In additional cells, no HDL is added. The cells are maintained for 24 hours, and intracellular cholesterol is assessed. The cholesterol efflux represents the amount of cholesterol that was leached by HDL from each of our study groups. Thus, cells not exposed to any HDL will contain the highest intracellular cholesterol content. The amount of cholesterol in cells exposed to CKD HDL or control HDL reflects the efflux capacity of that HDL. This is expressed as percent of cholesterol removed by HDL.</description>
        <time_frame>Once, at enrollment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CKD Not on Dialysis</title>
            <description>Patients with CKD not on dialysis (CKD III-IV)</description>
          </group>
          <group group_id="O2">
            <title>Controls</title>
            <description>Controls with normal kidney function (Control)</description>
          </group>
        </group_list>
        <measure>
          <title>In Vitro Lipoprotein Functions</title>
          <description>Cholesterol efflux. Baseline and outcome measurements are the same. The cholesterol efflux was measured once using HDL isolated from CKD and control patients. There was no intervention,this assessment was performed once in each group. The measurement of cholesterol efflux is performed by an in vitro assay in cultured cells. Cells are loaded with cholesterol and maintained for 72 hours. The media of the cultured cells is then changed and the new media contains HDL from CKD or control patients. In additional cells, no HDL is added. The cells are maintained for 24 hours, and intracellular cholesterol is assessed. The cholesterol efflux represents the amount of cholesterol that was leached by HDL from each of our study groups. Thus, cells not exposed to any HDL will contain the highest intracellular cholesterol content. The amount of cholesterol in cells exposed to CKD HDL or control HDL reflects the efflux capacity of that HDL. This is expressed as percent of cholesterol removed by HDL.</description>
          <units>Percentage of cholesterol content</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.8" lower_limit="16.1" upper_limit="23.7"/>
                    <measurement group_id="O2" value="26.5" lower_limit="19.6" upper_limit="28.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>CKD Not on Dialysis</title>
          <description>Patients with CKD not on dialysis (CKD III-IV)</description>
        </group>
        <group group_id="E2">
          <title>Controls</title>
          <description>Controls with normal kidney function (Control)</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="72"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Valentina Kon</name_or_title>
      <organization>Vanderbilt University Medical Center</organization>
      <phone>6153224883</phone>
      <email>valentina.kon@vanderbilt.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01671605
org study id: 090846
nct id: NCT01671605
lead sponsor: 
collaborator: 
has dmc: Yes
There is currently little understanding of macrophage cholesterol homeostasis and foam cell
      formation across the spectrum of CKD. We hypothesize that an inverse relationship exist
      between the severity of CKD and processes underlying foam cell formation, and that the
      relationship becomes independent of serum lipoprotein levels as renal function declines. We
      propose to systematically examine scavenger receptors and cholesterol uptake as well as
      cholesterol transporters and efflux mechanisms in individuals with normal renal function,
      patients with moderate CKD. We further propose to determine if processed contributing to foam
      cell formation are related to the plasma lipid profile and if the relationship is modified by
      co-morbidities, such as diabetes, obesity, systemic inflammation which are common in this
      population and directly influence vascular integrity. These data will be critically important
      to understand when the abnormality starts and will provide crucial information.
observational model: Case-Only
time perspective: Retrospective
measure: In Vitro Lipoprotein Functions
time frame: Once, at enrollment
description: Cholesterol efflux. Baseline and outcome measurements are the same. The cholesterol efflux was measured once using HDL isolated from CKD and control patients. There was no intervention,this assessment was performed once in each group. The measurement of cholesterol efflux is performed by an in vitro assay in cultured cells. Cells are loaded with cholesterol and maintained for 72 hours. The media of the cultured cells is then changed and the new media contains HDL from CKD or control patients. In additional cells, no HDL is added. The cells are maintained for 24 hours, and intracellular cholesterol is assessed. The cholesterol efflux represents the amount of cholesterol that was leached by HDL from each of our study groups. Thus, cells not exposed to any HDL will contain the highest intracellular cholesterol content. The amount of cholesterol in cells exposed to CKD HDL or control HDL reflects the efflux capacity of that HDL. This is expressed as percent of cholesterol removed by HDL.
arm group label: CKD not on dialysis
description: Patients with CKD not on dialysis (CKD III-IV)
arm group label: Controls
description: Controls with normal kidney function (Control)
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Valentina Kon, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University
investigator full name: Valentina Kon
investigator title: Principal Investigator
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Cardiovascular Diseases
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 