<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/NCT01733953</url>
  </required_header>
  <id_info>
    <org_study_id>1207M17202</org_study_id>
    <nct_id>NCT01733953</nct_id>
  </id_info>
  <brief_title>Statin Therapy in Young Adult Survivors of Childhood Cancer</brief_title>
  <official_title>Pilot Study of Statin Therapy in Young Adult Survivors of Childhood Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Adult survivors of childhood cancer are at high risk of developing cardiovascular disease.&#xD;
      Therapies used to treat many cancers, such as chemotherapy and radiation, likely cause damage&#xD;
      to the surface of the artery wall called the endothelial layer, leading to the induction of&#xD;
      atherosclerosis and eventual cardiovascular disease. HMG coenzyme A reductase inhibitors, or&#xD;
      statins, improve endothelial function independent of cholesterol-lowering. In addition,&#xD;
      statins have been shown to reduce arterial stiffness and slow arterial thickening. Despite&#xD;
      strong evidence supporting the vascular benefits of statins in many different patient&#xD;
      populations, these medications have never been studied in cancer survivors. Therefore, the&#xD;
      overall objective of this study is to evaluate the effects of statin therapy on vascular&#xD;
      health in young adult survivors of childhood cancer.&#xD;
&#xD;
      Twenty-four young adult (age 18-39 years old) survivors of childhood acute lymphoblastic&#xD;
      leukemia (ALL) or non-Hodgkin's lymphoma (NHL) will be enrolled in a six-month randomized,&#xD;
      double-blind (participants and investigators), placebo-controlled pilot clinical trial&#xD;
      comparing the effects of atorvastatin versus placebo on endothelial function and other&#xD;
      measures of vascular health.&#xD;
&#xD;
      Our primary objective is to evaluate the effects of 6-months of statin therapy on conduit&#xD;
      artery endothelial function in young adult survivors of childhood cancer. The investigators&#xD;
      hypothesize that, compared to placebo, atorvastatin will significantly increase brachial&#xD;
      artery flow-mediated dilation in survivors of childhood acute lymphoblastic leukemia and&#xD;
      non-Hodgkin's lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Adult survivors of childhood cancer are at seven times the risk of dying from cardiovascular&#xD;
      disease compared to the general population. The increased risk is thought to be the result of&#xD;
      the therapies used to treat the cancer such as chemotherapy and radiation. These therapies&#xD;
      likely cause damage to the endothelial cells, which line the arterial wall and, when function&#xD;
      properly, offer protection from atherosclerosis. Young adult survivors of childhood ALL have&#xD;
      reduced endothelial function, or endothelial dysfunction, compared to healthy controls.&#xD;
      Endothelial dysfunction is considered an early manifestation of atherosclerosis and therefore&#xD;
      is an ideal target of therapy in order to reduce the risk of cardiovascular disease.&#xD;
      Interventions that improve endothelial function in young adult survivors of childhood cancer&#xD;
      may be beneficial in terms of mitigating the medium- and long-term risk of developing this&#xD;
      chronic disease.&#xD;
&#xD;
      HMG coenzyme A reductase inhibitors, or statins, are widely used for cardiovascular disease&#xD;
      risk reduction. These medications are primarily used to reduce levels of total- and&#xD;
      low-density lipoprotein (LDL) -cholesterol. Meta-analyses have consistently demonstrated that&#xD;
      statin therapy improves endothelial function in a wide array of patient populations. Beyond&#xD;
      their well-described vascular benefits, statins are an attractive therapeutic option for&#xD;
      cardiovascular disease risk reduction due to their strong safety profile.&#xD;
&#xD;
      Despite the clear potential for endothelial function improvement and cardiovascular risk&#xD;
      reduction, statin therapy has never been evaluated in survivors of childhood cancer. Although&#xD;
      statins have been well-studied in other patient populations at risk for cardiovascular&#xD;
      disease, there is strong justification for evaluation in cancer survivors since the&#xD;
      mechanisms responsible for the vascular problems in these individuals (treatment-induced&#xD;
      vascular toxicity) differ from traditional atherosclerosis. Therefore, the objective of the&#xD;
      current study is to assess the ability of statin therapy to improve endothelial function,&#xD;
      arterial stiffness, and arterial thickening in young adult survivors of childhood cancer. The&#xD;
      focus of the study will be on survivors of hematologic malignancies, acute lymphoblastic&#xD;
      leukemia (ALL) and non-Hodgkin's lymphoma (NHL), since the former has been shown to be&#xD;
      associated with endothelial impairments and both cancers share common treatment exposures&#xD;
      (chemotherapy and radiation), which is likely the primary factor responsible for endothelial&#xD;
      dysfunction in these individuals.&#xD;
&#xD;
      Twenty-four young adult (age 18-39 years old) survivors of childhood acute lymphoblastic&#xD;
      leukemia (ALL) and non-Hodgkin's lymphoma (NHL)will be enrolled in a six-month randomized,&#xD;
      double-blind (participants and investigators), placebo-controlled pilot clinical trial&#xD;
      comparing the effects of atorvastatin versus placebo on endothelial function and other&#xD;
      measures of vascular health. Following baseline testing, subjects will be randomly assigned&#xD;
      (1:1) to either atorvastatin or placebo. Participants will return at 1-month and 3-months for&#xD;
      assessment of safety (blood draw and adverse event assessment) and medication compliance and&#xD;
      at 6-months for assessment of safety, medication compliance, and reassessment of baseline&#xD;
      variables.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">November 2015</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Brachial Artery Flow-Mediated Dilation at 6-months</measure>
    <time_frame>Baseline and 6-Months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Carotid Artery Compliance at 6-Months</measure>
    <time_frame>Baseline and 6-Months</time_frame>
    <description>Carotid Artery Compliance is a measure of arterial stiffness. Higher arterial stiffness places persons at higher risk for CVD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Carotid Artery Distensibility at 6-Months</measure>
    <time_frame>Baseline and 6-Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pulse Wave Velocity at 6-Months</measure>
    <time_frame>Baseline and 6-Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Augmentation Index at 6-Months</measure>
    <time_frame>Baseline and 6-Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Carotid Intima-Media Thickness at 6-Months</measure>
    <time_frame>Baseline and 6-Months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Cardiovascular Disease</condition>
  <condition>Childhood ALL</condition>
  <condition>Childhood NHL</condition>
  <arm_group>
    <arm_group_label>Atorvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6-Months Atorvastatin Therapy; 40mg oral, once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar Pill (Placebo)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>6-Months Placebo (sugar pill); oral, once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin</intervention_name>
    <description>6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.</description>
    <arm_group_label>Atorvastatin</arm_group_label>
    <other_name>Lipitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sugar Pill (Placebo)</intervention_name>
    <description>6-Months of placebo (sugar) pill; oral, once daily</description>
    <arm_group_label>Sugar Pill (Placebo)</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Survivor of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkins's lymphoma&#xD;
             (NHL) (treated for ALL or NHL before the age of 21 years old and ≥5 years&#xD;
             post-treatment)&#xD;
&#xD;
          -  18-39 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 1 or 2 diabetes mellitus&#xD;
&#xD;
          -  Prior treatment with hematopoietic stem cell transplant&#xD;
&#xD;
          -  Low-density lipoprotein (LDL) -cholesterol ≥130 mg/dL (individuals with elevated&#xD;
             LDL-cholesterol will be referred for clinical management of dyslipidemia)&#xD;
&#xD;
          -  Alanine transaminase (ALT), Aspartate transaminase (AST), or Creatine kinase (CK)&#xD;
             greater than 2 times the upper limit of normal&#xD;
&#xD;
          -  Current or recent (within 6-months) use of lipid-lowering medication&#xD;
&#xD;
          -  Recent initiation (within 6-months) of anti-hypertensive medication (individuals on&#xD;
             stable therapy may be enrolled)&#xD;
&#xD;
          -  Current or recent (within 6-months) use of fibric acid derivatives, lipid-modifying&#xD;
             doses of niacin, cyclosporine or strong CYP3A4 inhibitors (i.e. clarithromycin, HIV&#xD;
             protease inhibitors, and itraconazole)&#xD;
&#xD;
          -  Pregnant, lactating or planning to become pregnant&#xD;
&#xD;
          -  Liver/renal dysfunction&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>39 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aaron S Kelly, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <results_first_submitted>April 11, 2016</results_first_submitted>
  <results_first_submitted_qc>August 19, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 14, 2016</results_first_posted>
  <last_update_submitted>October 28, 2016</last_update_submitted>
  <last_update_submitted_qc>October 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cardiovascular Disease</keyword>
  <keyword>Childhood ALL</keyword>
  <keyword>Childhood NHL</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atorvastatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>At this time we have no plan to share the IPD.</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Atorvastatin</title>
          <description>6-Months Atorvastatin Therapy; 40mg oral, once daily&#xD;
Atorvastatin: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.</description>
        </group>
        <group group_id="P2">
          <title>Sugar Pill (Placebo)</title>
          <description>6-Months Placebo (sugar pill); oral, once daily&#xD;
Sugar Pill (Placebo): 6-Months of placebo (sugar) pill; oral, once daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Atorvastatin</title>
          <description>6-Months Atorvastatin Therapy; 40mg oral, once daily&#xD;
Atorvastatin: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.</description>
        </group>
        <group group_id="B2">
          <title>Sugar Pill (Placebo)</title>
          <description>6-Months Placebo (sugar pill); oral, once daily&#xD;
Sugar Pill (Placebo): 6-Months of placebo (sugar) pill; oral, once daily</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="14"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="27"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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>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="26.6" spread="5.7"/>
                    <measurement group_id="B2" value="26.9" spread="6.9"/>
                    <measurement group_id="B3" value="26.8" spread="6.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="8"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="14"/>
                  </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="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Brachial Artery Flow-Mediated Dilation at 6-months</title>
        <time_frame>Baseline and 6-Months</time_frame>
        <population>Physician withdrawals, loss to follow-up, drug compliance &lt;70%, unrelated injury, and self-withdrawal reduced number analyzed. Also, participant movement during FMD assessment and/or poor ultrasound image quality due to difficult brachial artery anatomy or poor circulation led to some unusable data and thus lowered the analyzable sample size.</population>
        <group_list>
          <group group_id="O1">
            <title>Atorvastatin</title>
            <description>6-Months Atorvastatin Therapy; 40mg oral, once daily&#xD;
Atorvastatin: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill (Placebo)</title>
            <description>6-Months Placebo (sugar pill); oral, once daily&#xD;
Sugar Pill (Placebo): 6-Months of placebo (sugar) pill; oral, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Brachial Artery Flow-Mediated Dilation at 6-months</title>
          <population>Physician withdrawals, loss to follow-up, drug compliance &lt;70%, unrelated injury, and self-withdrawal reduced number analyzed. Also, participant movement during FMD assessment and/or poor ultrasound image quality due to difficult brachial artery anatomy or poor circulation led to some unusable data and thus lowered the analyzable sample size.</population>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" lower_limit="-2.9" upper_limit="1.9"/>
                    <measurement group_id="O2" value="-3.4" lower_limit="-7.3" upper_limit="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Carotid Artery Compliance at 6-Months</title>
        <description>Carotid Artery Compliance is a measure of arterial stiffness. Higher arterial stiffness places persons at higher risk for CVD.</description>
        <time_frame>Baseline and 6-Months</time_frame>
        <population>Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>Atorvastatin</title>
            <description>6-Months Atorvastatin Therapy; 40mg oral, once daily&#xD;
Atorvastatin: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill (Placebo)</title>
            <description>6-Months Placebo (sugar pill); oral, once daily&#xD;
Sugar Pill (Placebo): 6-Months of placebo (sugar) pill; oral, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Carotid Artery Compliance at 6-Months</title>
          <description>Carotid Artery Compliance is a measure of arterial stiffness. Higher arterial stiffness places persons at higher risk for CVD.</description>
          <population>Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.</population>
          <units>mm/mmHg x 10^-3</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.34" lower_limit="-1.4" upper_limit="0.7"/>
                    <measurement group_id="O2" value="0.57" lower_limit="-.8" upper_limit="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Carotid Artery Distensibility at 6-Months</title>
        <time_frame>Baseline and 6-Months</time_frame>
        <population>Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>Atorvastatin</title>
            <description>6-Months Atorvastatin Therapy; 40mg oral, once daily&#xD;
Atorvastatin: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill (Placebo)</title>
            <description>6-Months Placebo (sugar pill); oral, once daily&#xD;
Sugar Pill (Placebo): 6-Months of placebo (sugar) pill; oral, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Carotid Artery Distensibility at 6-Months</title>
          <population>Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.</population>
          <units>% distensibility</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.31" lower_limit="-1.28" upper_limit="1.9"/>
                    <measurement group_id="O2" value="0.33" lower_limit="-1.81" upper_limit="2.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Pulse Wave Velocity at 6-Months</title>
        <time_frame>Baseline and 6-Months</time_frame>
        <population>Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>Atorvastatin</title>
            <description>6-Months Atorvastatin Therapy; 40mg oral, once daily&#xD;
Atorvastatin: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill (Placebo)</title>
            <description>6-Months Placebo (sugar pill); oral, once daily&#xD;
Sugar Pill (Placebo): 6-Months of placebo (sugar) pill; oral, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Pulse Wave Velocity at 6-Months</title>
          <population>Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.</population>
          <units>m/s</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.52" lower_limit="-2.06" upper_limit="1.02"/>
                    <measurement group_id="O2" value="-0.3" lower_limit="-2.36" upper_limit="1.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Augmentation Index at 6-Months</title>
        <time_frame>Baseline and 6-Months</time_frame>
        <population>Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>Atorvastatin</title>
            <description>6-Months Atorvastatin Therapy; 40mg oral, once daily&#xD;
Atorvastatin: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill (Placebo)</title>
            <description>6-Months Placebo (sugar pill); oral, once daily&#xD;
Sugar Pill (Placebo): 6-Months of placebo (sugar) pill; oral, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Augmentation Index at 6-Months</title>
          <population>Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.</population>
          <units>P2/P1</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.66" lower_limit="-15.38" upper_limit="14.06"/>
                    <measurement group_id="O2" value="-6.01" lower_limit="-24.16" upper_limit="12.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Carotid Intima-Media Thickness at 6-Months</title>
        <time_frame>Baseline and 6-Months</time_frame>
        <population>Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.</population>
        <group_list>
          <group group_id="O1">
            <title>Atorvastatin</title>
            <description>6-Months Atorvastatin Therapy; 40mg oral, once daily&#xD;
Atorvastatin: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill (Placebo)</title>
            <description>6-Months Placebo (sugar pill); oral, once daily&#xD;
Sugar Pill (Placebo): 6-Months of placebo (sugar) pill; oral, once daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Carotid Intima-Media Thickness at 6-Months</title>
          <population>Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.01" lower_limit="-.03" upper_limit="0.01"/>
                    <measurement group_id="O2" value="0.01" lower_limit="-0.02" upper_limit="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Atorvastatin</title>
          <description>6-Months Atorvastatin Therapy; 40mg oral, once daily&#xD;
Atorvastatin: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.</description>
        </group>
        <group group_id="E2">
          <title>Sugar Pill (Placebo)</title>
          <description>6-Months Placebo (sugar pill); oral, once daily&#xD;
Sugar Pill (Placebo): 6-Months of placebo (sugar) pill; oral, once daily</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="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </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="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </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>Cameron Naughton</name_or_title>
      <organization>University of Minnesota</organization>
      <phone>612-625-3623</phone>
      <email>naug0009@umn.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/NCT01733953
org study id: 1207M17202
nct id: NCT01733953
lead sponsor: 
has dmc: Yes
Adult survivors of childhood cancer are at high risk of developing cardiovascular disease.
      Therapies used to treat many cancers, such as chemotherapy and radiation, likely cause damage
      to the surface of the artery wall called the endothelial layer, leading to the induction of
      atherosclerosis and eventual cardiovascular disease. HMG coenzyme A reductase inhibitors, or
      statins, improve endothelial function independent of cholesterol-lowering. In addition,
      statins have been shown to reduce arterial stiffness and slow arterial thickening. Despite
      strong evidence supporting the vascular benefits of statins in many different patient
      populations, these medications have never been studied in cancer survivors. Therefore, the
      overall objective of this study is to evaluate the effects of statin therapy on vascular
      health in young adult survivors of childhood cancer.

      Twenty-four young adult (age 18-39 years old) survivors of childhood acute lymphoblastic
      leukemia (ALL) or non-Hodgkin's lymphoma (NHL) will be enrolled in a six-month randomized,
      double-blind (participants and investigators), placebo-controlled pilot clinical trial
      comparing the effects of atorvastatin versus placebo on endothelial function and other
      measures of vascular health.

      Our primary objective is to evaluate the effects of 6-months of statin therapy on conduit
      artery endothelial function in young adult survivors of childhood cancer. The investigators
      hypothesize that, compared to placebo, atorvastatin will significantly increase brachial
      artery flow-mediated dilation in survivors of childhood acute lymphoblastic leukemia and
      non-Hodgkin's lymphoma.
Adult survivors of childhood cancer are at seven times the risk of dying from cardiovascular
      disease compared to the general population. The increased risk is thought to be the result of
      the therapies used to treat the cancer such as chemotherapy and radiation. These therapies
      likely cause damage to the endothelial cells, which line the arterial wall and, when function
      properly, offer protection from atherosclerosis. Young adult survivors of childhood ALL have
      reduced endothelial function, or endothelial dysfunction, compared to healthy controls.
      Endothelial dysfunction is considered an early manifestation of atherosclerosis and therefore
      is an ideal target of therapy in order to reduce the risk of cardiovascular disease.
      Interventions that improve endothelial function in young adult survivors of childhood cancer
      may be beneficial in terms of mitigating the medium- and long-term risk of developing this
      chronic disease.

      HMG coenzyme A reductase inhibitors, or statins, are widely used for cardiovascular disease
      risk reduction. These medications are primarily used to reduce levels of total- and
      low-density lipoprotein (LDL) -cholesterol. Meta-analyses have consistently demonstrated that
      statin therapy improves endothelial function in a wide array of patient populations. Beyond
      their well-described vascular benefits, statins are an attractive therapeutic option for
      cardiovascular disease risk reduction due to their strong safety profile.

      Despite the clear potential for endothelial function improvement and cardiovascular risk
      reduction, statin therapy has never been evaluated in survivors of childhood cancer. Although
      statins have been well-studied in other patient populations at risk for cardiovascular
      disease, there is strong justification for evaluation in cancer survivors since the
      mechanisms responsible for the vascular problems in these individuals (treatment-induced
      vascular toxicity) differ from traditional atherosclerosis. Therefore, the objective of the
      current study is to assess the ability of statin therapy to improve endothelial function,
      arterial stiffness, and arterial thickening in young adult survivors of childhood cancer. The
      focus of the study will be on survivors of hematologic malignancies, acute lymphoblastic
      leukemia (ALL) and non-Hodgkin's lymphoma (NHL), since the former has been shown to be
      associated with endothelial impairments and both cancers share common treatment exposures
      (chemotherapy and radiation), which is likely the primary factor responsible for endothelial
      dysfunction in these individuals.

      Twenty-four young adult (age 18-39 years old) survivors of childhood acute lymphoblastic
      leukemia (ALL) and non-Hodgkin's lymphoma (NHL)will be enrolled in a six-month randomized,
      double-blind (participants and investigators), placebo-controlled pilot clinical trial
      comparing the effects of atorvastatin versus placebo on endothelial function and other
      measures of vascular health. Following baseline testing, subjects will be randomly assigned
      (1:1) to either atorvastatin or placebo. Participants will return at 1-month and 3-months for
      assessment of safety (blood draw and adverse event assessment) and medication compliance and
      at 6-months for assessment of safety, medication compliance, and reassessment of baseline
      variables.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Brachial Artery Flow-Mediated Dilation at 6-months
time frame: Baseline and 6-Months
measure: Change From Baseline in Carotid Artery Compliance at 6-Months
time frame: Baseline and 6-Months
description: Carotid Artery Compliance is a measure of arterial stiffness. Higher arterial stiffness places persons at higher risk for CVD.
measure: Change From Baseline in Carotid Artery Distensibility at 6-Months
time frame: Baseline and 6-Months
measure: Change From Baseline in Pulse Wave Velocity at 6-Months
time frame: Baseline and 6-Months
measure: Change From Baseline in Augmentation Index at 6-Months
time frame: Baseline and 6-Months
measure: Change From Baseline in Carotid Intima-Media Thickness at 6-Months
time frame: Baseline and 6-Months
arm group label: Atorvastatin
arm group type: Experimental
description: 6-Months Atorvastatin Therapy; 40mg oral, once daily
arm group label: Sugar Pill (Placebo)
arm group type: Placebo Comparator
description: 6-Months Placebo (sugar pill); oral, once daily
intervention type: Drug
intervention name: Atorvastatin
description: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.
arm group label: Atorvastatin
other name: Lipitor
intervention type: Drug
intervention name: Sugar Pill (Placebo)
description: 6-Months of placebo (sugar) pill; oral, once daily
arm group label: Sugar Pill (Placebo)
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 39 Years
healthy volunteers: No
last name: Aaron S Kelly, Ph.D.
role: Principal Investigator
affiliation: University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Cardiovascular Diseases
mesh term: Atorvastatin
sharing ipd: No
ipd description: At this time we have no plan to share the IPD.
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 