<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/NCT01663103</url>
  </required_header>
  <id_info>
    <org_study_id>12-0586</org_study_id>
    <nct_id>NCT01663103</nct_id>
  </id_info>
  <brief_title>Interleukin-1 Trap to Treat Vascular Dysfunction in Chronic Kidney Disease (CKD)</brief_title>
  <official_title>Interleukin-1 Trap to Treat Vascular Dysfunction in Chronic Kidney Disease (CKD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Risk of cardiovascular diseases (CVD) is significantly elevated in patients with chronic&#xD;
      kidney disease (CKD); however, this increased risk is only partially explained by traditional&#xD;
      cardiovascular risk factors. Patients with CKD exhibit chronic inflammation, a key mechanism&#xD;
      contributing to vascular dysfunction (i.e., large elastic artery stiffening and endothelial&#xD;
      dysfunction). Inhibiting inflammation improves vascular dysfunction in other populations&#xD;
      characterized by chronic inflammation. However, it is currently unknown if reducing&#xD;
      inflammation with an interleukin-1 (IL-1) blocker enhances vascular function in CKD patients.&#xD;
      Aim 1 will assess the efficacy of IL-1 blocking with rilonacept for treating vascular&#xD;
      dysfunction in patients with stage III or IV CKD (estimated glomerular filtration rate 15-60&#xD;
      mL/min/1.73 m2). Aim 2 will determine if blocking IL-1 with rilonacept also reduces&#xD;
      inflammation and oxidative stress. These studies could shift clinical practice guidelines by&#xD;
      establishing a novel therapy for reducing CVD risk in CKD patients not requiring chronic&#xD;
      hemodialysis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Flow-mediated Dilation (FMD)</measure>
    <time_frame>3 months after start of treatment</time_frame>
    <description>Change in FMD after 3 months of treatment with rilonacept will be compared to change in the placebo group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Aortic Pulse-wave Velocity (aPWV)</measure>
    <time_frame>3 months after start of treatment</time_frame>
    <description>Change in aPWV after 3 months of treatment with rilonacept will be compared to change in the placebo group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Contribution of Oxidative Stress to FMD</measure>
    <time_frame>3 months after start of treatment</time_frame>
    <description>FMD will be assessed following acute infusion of ascorbic acid compared to saline. The improvement in FMD with ascorbic acid reflects the degree of oxidative stress contributing to impairment in FMD.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in High-sensitivity C-reactive Protein (hsCRP)</measure>
    <time_frame>3 months after start of treatment</time_frame>
    <description>Change in high-sensitivity C-reactive protein (hsCRP) after 3 months of rilonacept vs. placebo will be assessed as a circulating marker of inflammation.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Vascular Endothelial NADPH Oxidase Expression</measure>
    <time_frame>3 months after start of treatment</time_frame>
    <description>Vascular endothelial cells will be collected and assessed for changes in protein expression of NADPH oxidase after 3 months of treatment with rilonacept vs. placebo. Protein expression is calculated as a ratio of intensity of staining in the patient cells relative to human umbilical vein endothelial cell (HUVEC) control cells. The absolute change in this ratio between baseline and week 12 is reported below.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Renal Insufficiency, Chronic</condition>
  <arm_group>
    <arm_group_label>Rilonacept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>12 weeks of treatment with rilonacept</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Twelve weeks of treatment with placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rilonacept</intervention_name>
    <description>12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)</description>
    <arm_group_label>Rilonacept</arm_group_label>
    <other_name>Arcalyst</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-80 years&#xD;
&#xD;
          -  CKD stage III or IV (eGFR with the 4-variable Modified Diet Renal Disease (MDRD)&#xD;
             prediction equation: 15-60 mL/min/1.73m2; stable renal function in the past 3 months)&#xD;
&#xD;
          -  An elevated high sensitivity C-reactive protein (hs-CRP) of &gt; 2.0 mg/L and &lt;30 mg/L on&#xD;
             at least 2 consecutive weekly determinations&#xD;
&#xD;
          -  Urine protein excretion &lt; 5.0 g/24h estimated by a spot urine protein/creatinine ratio&#xD;
&#xD;
          -  Ability to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with advanced CKD requiring chronic dialysis&#xD;
&#xD;
          -  Active infection (chronic or acute (within 3 months) or antibiotic therapy (w/in 1&#xD;
             mo); history of recurrent infection&#xD;
&#xD;
          -  Significant co-morbid conditions that lead the investigator to conclude that life&#xD;
             expectancy is less than 1 year&#xD;
&#xD;
          -  Expected to undergo living related transplant in next 6 months&#xD;
&#xD;
          -  History of severe congestive heart failure (i.e., EF &lt; 35%)&#xD;
&#xD;
          -  Hospitalization in the past month&#xD;
&#xD;
          -  Severe arthritis, lupus, inflammatory bowel disease, asthma or other disease(s) or&#xD;
             medical condition(s) that, in the opinion of the investigator, could interfere with&#xD;
             hsCRP or immune function&#xD;
&#xD;
          -  Immunosuppressant agents such as cyclosporine, tacrolimus, azathioprine, etanercept,&#xD;
             infliximab, adalimumab, anakinra or long-term oral glucocorticoids taken in past 12&#xD;
             months&#xD;
&#xD;
          -  Known malignancy&#xD;
&#xD;
          -  HIV, active, chronic hepatitis B as evidenced by HBsAg positive and HBsAb negative, or&#xD;
             hepatitis C positive&#xD;
&#xD;
          -  Woman who are pregnant, nursing or planning to become pregnant&#xD;
&#xD;
          -  Body mass index (BMI) &gt;40 kg/m2&#xD;
&#xD;
          -  Warfarin use (or other cytochrome P (CYP)450 substrates with a narrow therapeutic&#xD;
             index) [ok if do not participate in endothelial cell collection]&#xD;
&#xD;
          -  Taking medication(s) that interact with agents administered during experimental&#xD;
             sessions (e.g., sildenafil interacts with nitroglycerin)&#xD;
&#xD;
          -  Currently receiving or planning to receive live or inactivated vaccines&#xD;
&#xD;
          -  Alcohol dependence or abuse&#xD;
&#xD;
          -  Subjects at risk for tuberculosis (TB). Specifically, subjects with:&#xD;
&#xD;
          -  Current clinical, radiographic or laboratory evidence of active TB at screening or&#xD;
             latent TB that has not been previously treated&#xD;
&#xD;
          -  A history of active TB within the last 3 years even if it was treated.&#xD;
&#xD;
          -  A history of active TB greater than 3 years ago unless there is documentation that the&#xD;
             prior anti-TB treatment was appropriate in duration and type.&#xD;
&#xD;
          -  Therapy for latent TB which has not been completed as per local guidelines.&#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>Kristen L Jablonski Nowak, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado Denver Anschutz Medical Campus</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado Clinical and Translational Research Center (CTRC) Outpatient Clinic</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical 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>June 2016</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <results_first_submitted>April 6, 2016</results_first_submitted>
  <results_first_submitted_qc>August 2, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 12, 2016</results_first_posted>
  <last_update_submitted>August 2, 2016</last_update_submitted>
  <last_update_submitted_qc>August 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 12, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Interleukin-1</keyword>
  <keyword>Endothelium, Vascular</keyword>
  <keyword>Vascular Stiffness</keyword>
  <keyword>Oxidative Stress</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Endothelial cells</keyword>
  <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>Renal Insufficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rilonacept</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Rilonacept</title>
          <description>12 weeks of treatment with rilonacept&#xD;
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Twelve weeks of treatment with placebo&#xD;
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>dog bite</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Rilonacept</title>
          <description>12 weeks of treatment with rilonacept&#xD;
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Twelve weeks of treatment with placebo&#xD;
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)</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="21"/>
            <count group_id="B2" value="21"/>
            <count group_id="B3" value="42"/>
          </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" spread="11"/>
                    <measurement group_id="B2" value="65" spread="11"/>
                    <measurement group_id="B3" value="63" spread="11"/>
                  </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="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Etiology of CKD</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Type II Diabetes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Type I DIabetes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Autosomal Dominant Polycystic Kidney Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Renal Cell Carcinoma</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Focal Segmental Glomerulosclerosis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Estimated glomerular filtration rate</title>
          <units>mL/min/1.73m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38" spread="14"/>
                    <measurement group_id="B2" value="38" spread="12"/>
                    <measurement group_id="B3" value="38" spread="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Flow-mediated Dilation (FMD)</title>
        <description>Change in FMD after 3 months of treatment with rilonacept will be compared to change in the placebo group.</description>
        <time_frame>3 months after start of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rilonacept</title>
            <description>12 weeks of treatment with rilonacept&#xD;
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Twelve weeks of treatment with placebo&#xD;
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Flow-mediated Dilation (FMD)</title>
          <description>Change in FMD after 3 months of treatment with rilonacept will be compared to change in the placebo group.</description>
          <units>change in percent flow-mediated dilation</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="3.2"/>
                    <measurement group_id="O2" value="-0.9" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Aortic Pulse-wave Velocity (aPWV)</title>
        <description>Change in aPWV after 3 months of treatment with rilonacept will be compared to change in the placebo group.</description>
        <time_frame>3 months after start of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rilonacept</title>
            <description>12 weeks of treatment with rilonacept&#xD;
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Twelve weeks of treatment with placebo&#xD;
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Aortic Pulse-wave Velocity (aPWV)</title>
          <description>Change in aPWV after 3 months of treatment with rilonacept will be compared to change in the placebo group.</description>
          <units>change in pulse-wave velocity (cm/sec)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12" spread="65"/>
                    <measurement group_id="O2" value="2" spread="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Contribution of Oxidative Stress to FMD</title>
        <description>FMD will be assessed following acute infusion of ascorbic acid compared to saline. The improvement in FMD with ascorbic acid reflects the degree of oxidative stress contributing to impairment in FMD.</description>
        <time_frame>3 months after start of treatment</time_frame>
        <population>sub-group from Denver site</population>
        <group_list>
          <group group_id="O1">
            <title>Rilonacept: Baseline</title>
            <description>Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the rilonacept group at baseline.</description>
          </group>
          <group group_id="O2">
            <title>Rilonacept: End of Study</title>
            <description>Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the rilonacept group at 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Placebo: Baseline</title>
            <description>Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline</description>
          </group>
          <group group_id="O4">
            <title>Placebo: End of Study</title>
            <description>Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Contribution of Oxidative Stress to FMD</title>
          <description>FMD will be assessed following acute infusion of ascorbic acid compared to saline. The improvement in FMD with ascorbic acid reflects the degree of oxidative stress contributing to impairment in FMD.</description>
          <population>sub-group from Denver site</population>
          <units>change in percent flow-mediated dilation</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="13"/>
                <count group_id="O4" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.16" spread="2.52"/>
                    <measurement group_id="O2" value="0.51" spread="2.24"/>
                    <measurement group_id="O3" value="-0.04" spread="1.96"/>
                    <measurement group_id="O4" value="0.69" spread="1.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in High-sensitivity C-reactive Protein (hsCRP)</title>
        <description>Change in high-sensitivity C-reactive protein (hsCRP) after 3 months of rilonacept vs. placebo will be assessed as a circulating marker of inflammation.</description>
        <time_frame>3 months after start of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rilonacept</title>
            <description>12 weeks of treatment with rilonacept&#xD;
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Twelve weeks of treatment with placebo&#xD;
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in High-sensitivity C-reactive Protein (hsCRP)</title>
          <description>Change in high-sensitivity C-reactive protein (hsCRP) after 3 months of rilonacept vs. placebo will be assessed as a circulating marker of inflammation.</description>
          <units>change in c-reactive protein (mg/L)</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="16"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.02" lower_limit="-2.9" upper_limit="1.3"/>
                    <measurement group_id="O2" value="0.16" lower_limit="-0.82" upper_limit="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Vascular Endothelial NADPH Oxidase Expression</title>
        <description>Vascular endothelial cells will be collected and assessed for changes in protein expression of NADPH oxidase after 3 months of treatment with rilonacept vs. placebo. Protein expression is calculated as a ratio of intensity of staining in the patient cells relative to human umbilical vein endothelial cell (HUVEC) control cells. The absolute change in this ratio between baseline and week 12 is reported below.</description>
        <time_frame>3 months after start of treatment</time_frame>
        <population>sub-group from Denver site</population>
        <group_list>
          <group group_id="O1">
            <title>Rilonacept</title>
            <description>12 weeks of treatment with rilonacept&#xD;
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Twelve weeks of treatment with placebo&#xD;
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Vascular Endothelial NADPH Oxidase Expression</title>
          <description>Vascular endothelial cells will be collected and assessed for changes in protein expression of NADPH oxidase after 3 months of treatment with rilonacept vs. placebo. Protein expression is calculated as a ratio of intensity of staining in the patient cells relative to human umbilical vein endothelial cell (HUVEC) control cells. The absolute change in this ratio between baseline and week 12 is reported below.</description>
          <population>sub-group from Denver site</population>
          <units>absolute change in ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="0.03"/>
                    <measurement group_id="O2" value="0.01" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Rilonacept</title>
          <description>12 weeks of treatment with rilonacept&#xD;
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Twelve weeks of treatment with placebo&#xD;
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</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="5" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Neck abscess/pyomyositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
              </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>Dr. Kristen Nowak</name_or_title>
      <organization>University of Colorado Anschutz Medical Campus</organization>
      <phone>303-724-4842</phone>
      <email>Kristen.Nowak@ucdenver.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/NCT01663103
org study id: 12-0586
nct id: NCT01663103
lead sponsor: 
has dmc: Yes
Risk of cardiovascular diseases (CVD) is significantly elevated in patients with chronic
      kidney disease (CKD); however, this increased risk is only partially explained by traditional
      cardiovascular risk factors. Patients with CKD exhibit chronic inflammation, a key mechanism
      contributing to vascular dysfunction (i.e., large elastic artery stiffening and endothelial
      dysfunction). Inhibiting inflammation improves vascular dysfunction in other populations
      characterized by chronic inflammation. However, it is currently unknown if reducing
      inflammation with an interleukin-1 (IL-1) blocker enhances vascular function in CKD patients.
      Aim 1 will assess the efficacy of IL-1 blocking with rilonacept for treating vascular
      dysfunction in patients with stage III or IV CKD (estimated glomerular filtration rate 15-60
      mL/min/1.73 m2). Aim 2 will determine if blocking IL-1 with rilonacept also reduces
      inflammation and oxidative stress. These studies could shift clinical practice guidelines by
      establishing a novel therapy for reducing CVD risk in CKD patients not requiring chronic
      hemodialysis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in Flow-mediated Dilation (FMD)
time frame: 3 months after start of treatment
description: Change in FMD after 3 months of treatment with rilonacept will be compared to change in the placebo group.
measure: Change in Aortic Pulse-wave Velocity (aPWV)
time frame: 3 months after start of treatment
description: Change in aPWV after 3 months of treatment with rilonacept will be compared to change in the placebo group.
measure: Change in Contribution of Oxidative Stress to FMD
time frame: 3 months after start of treatment
description: FMD will be assessed following acute infusion of ascorbic acid compared to saline. The improvement in FMD with ascorbic acid reflects the degree of oxidative stress contributing to impairment in FMD.
measure: Change in High-sensitivity C-reactive Protein (hsCRP)
time frame: 3 months after start of treatment
description: Change in high-sensitivity C-reactive protein (hsCRP) after 3 months of rilonacept vs. placebo will be assessed as a circulating marker of inflammation.
measure: Change in Vascular Endothelial NADPH Oxidase Expression
time frame: 3 months after start of treatment
description: Vascular endothelial cells will be collected and assessed for changes in protein expression of NADPH oxidase after 3 months of treatment with rilonacept vs. placebo. Protein expression is calculated as a ratio of intensity of staining in the patient cells relative to human umbilical vein endothelial cell (HUVEC) control cells. The absolute change in this ratio between baseline and week 12 is reported below.
arm group label: Rilonacept
arm group type: Experimental
description: 12 weeks of treatment with rilonacept
arm group label: Placebo
arm group type: Placebo Comparator
description: Twelve weeks of treatment with placebo
intervention type: Drug
intervention name: Rilonacept
description: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
arm group label: Rilonacept
other name: Arcalyst
intervention type: Drug
intervention name: Placebo
description: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
arm group label: Placebo
other name: normal saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Kristen L Jablonski Nowak, Ph.D.
role: Principal Investigator
affiliation: University of Colorado Denver Anschutz Medical Campus
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Renal Insufficiency
mesh term: Rilonacept
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 