<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/NCT01702246</url>
  </required_header>
  <id_info>
    <org_study_id>DDCF-ICRA-2011</org_study_id>
    <nct_id>NCT01702246</nct_id>
  </id_info>
  <brief_title>Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease</brief_title>
  <official_title>Phase 2 Study of Simvastatin Treatment Effects on Vaso-occlusive Pain in Sickle Cell Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UCSF Benioff Children's Hospital Oakland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>UCSF Benioff Children's Hospital Oakland</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether simvastatin is effective in reducing the&#xD;
      frequency and intensity of vaso-occlusive pain episodes in patients with sickle cell disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive episodes and a chronic&#xD;
      inflammatory state leading to progressive multi-organ injury. The pathophysiology of SCD is&#xD;
      related to endothelial dysfunction driven largely by impaired nitric oxide (NO) homeostasis&#xD;
      and chronic inflammation. Through multiple mechanisms, including upregulation of NO, statins&#xD;
      have been shown to confer protection from endothelial injury, independent of their&#xD;
      cholesterol-lowering properties.&#xD;
&#xD;
      By inhibiting inflammation and several common pathways leading to vascular damage,simvastatin&#xD;
      may help prevent the acute and chronic complications of SCD. The objective of this study is&#xD;
      to determine whether our preliminary results showing simvastatin-associated reductions in&#xD;
      plasma markers of vascular injury will translate into a reduction in vaso-occlusive pain&#xD;
      episodes in patients with SCD. A web-based, smartphone-accessible electronic pain diary will&#xD;
      be used to monitor frequency and intensity of vaso-occlusive pain in SCD patients treated&#xD;
      with a single daily dose of simvastatin.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2012</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin</measure>
    <time_frame>Baseline and 3 months</time_frame>
    <description>The effect of simvastatin treatment will be assessed by measuring the difference from baseline in the mean frequency (and intensity) of vaso-occlusive pain events, after treatment with simvastatin. Pain rate (proportion of pain days) was defined as the number of days reported with sickle cell disease-related pain divided by the number of daily pain diaries completed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma High Sensitivity C-reactive Protein</measure>
    <time_frame>Baseline and 3 months</time_frame>
    <description>Mean difference in plasma high sensitivity C-reactive protein level, before and after treatment with simvastatin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin</measure>
    <time_frame>Baseline and 3 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Sickle Cell Disease</condition>
  <arm_group>
    <arm_group_label>simvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Simvastatin</intervention_name>
    <description>40 mg, orally, once daily for 3 months</description>
    <arm_group_label>simvastatin</arm_group_label>
    <other_name>Zocor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Sickle cell disease (HbSS or S/β0 thalassemia)&#xD;
&#xD;
          -  ≥ 3 vaso-occlusive pain episodes in the year prior to enrollment&#xD;
&#xD;
          -  Age ≥ 10 years&#xD;
&#xD;
          -  Weight &gt; 30 kg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Creatine kinase (CK) &gt; UNL&#xD;
&#xD;
          -  Total cholesterol &lt; 90 mg/dL, or triglycerides &lt;30mg/dL&#xD;
&#xD;
          -  Renal dysfunction (Creatinine &gt; 1.5-fold UNL)&#xD;
&#xD;
          -  Hepatic dysfunction (ALT &gt; 2-fold UNL)&#xD;
&#xD;
          -  Treatment with drugs having known metabolic interactions with statins within the past&#xD;
             30 days&#xD;
&#xD;
          -  Vaso-occlusive pain requiring hospitalization within past 30 days&#xD;
&#xD;
          -  Red blood cell transfusion within the past 30 days&#xD;
&#xD;
          -  Pregnancy/lactation&#xD;
&#xD;
          -  Musculoskeletal disorder associated with an elevated CK level&#xD;
&#xD;
          -  Past or present history of substance abuse (alcohol, cocaine, amphetamines, heroin)&#xD;
&#xD;
          -  Chronic pain caused by avascular necrosis of the bone (AVN) or leg ulcers, and pain&#xD;
             due to trauma or causes other than SCD.&#xD;
&#xD;
          -  Major cognitive or neurological impairments that may hamper the ability to use the&#xD;
             smartphone or complete the electronic pain diary in this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carolyn Hoppe, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UCSF Benioff Children's Hospital Oakland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital and Research Center Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Hoppe C, Kuypers F, Larkin S, Hagar W, Vichinsky E, Styles L. A pilot study of the short-term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction. Br J Haematol. 2011 Jun;153(5):655-63. doi: 10.1111/j.1365-2141.2010.08480.x. Epub 2011 Apr 8.</citation>
    <PMID>21477202</PMID>
  </reference>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <results_first_submitted>January 15, 2016</results_first_submitted>
  <results_first_submitted_qc>October 26, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 19, 2016</results_first_posted>
  <last_update_submitted>October 26, 2016</last_update_submitted>
  <last_update_submitted_qc>October 26, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>UCSF Benioff Children's Hospital Oakland</investigator_affiliation>
    <investigator_full_name>Carolyn Hoppe</investigator_full_name>
    <investigator_title>Associate Hematologist-Oncologist</investigator_title>
  </responsible_party>
  <keyword>sickle cell disease</keyword>
  <keyword>statins</keyword>
  <keyword>vaso-occlusive pain</keyword>
  <keyword>inflammation</keyword>
  <keyword>biomarkers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Simvastatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>publication</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Simvastatin</title>
          <description>Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months&#xD;
Simvastatin: 40 mg, orally, once daily for 3 months</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Simvastatin</title>
          <description>Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months&#xD;
Simvastatin: 40 mg, orally, once daily for 3 months</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
          </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="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" 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="18.5" spread="6.8"/>
                  </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="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Receiving hydroxyurea (HU) therapy</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin</title>
        <description>The effect of simvastatin treatment will be assessed by measuring the difference from baseline in the mean frequency (and intensity) of vaso-occlusive pain events, after treatment with simvastatin. Pain rate (proportion of pain days) was defined as the number of days reported with sickle cell disease-related pain divided by the number of daily pain diaries completed.</description>
        <time_frame>Baseline and 3 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Baseline</title>
            <description>prior to treatment with simvastatin</description>
          </group>
          <group group_id="O2">
            <title>Simvastatin</title>
            <description>after treatment with simvastatin: 40 mg, orally, once daily for 3 months</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin</title>
          <description>The effect of simvastatin treatment will be assessed by measuring the difference from baseline in the mean frequency (and intensity) of vaso-occlusive pain events, after treatment with simvastatin. Pain rate (proportion of pain days) was defined as the number of days reported with sickle cell disease-related pain divided by the number of daily pain diaries completed.</description>
          <units>proportion of pain days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2365" spread="0.21"/>
                    <measurement group_id="O2" value="0.1311" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.005</p_value>
            <p_value_desc>Wilcoxon matched pairs signed rank test</p_value_desc>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Plasma High Sensitivity C-reactive Protein</title>
        <description>Mean difference in plasma high sensitivity C-reactive protein level, before and after treatment with simvastatin</description>
        <time_frame>Baseline and 3 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Baseline</title>
            <description>prior to treatment with simvastatin</description>
          </group>
          <group group_id="O2">
            <title>Simvastatin</title>
            <description>after treatment with simvastatin: 40 mg, orally, once daily for 3 months</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Plasma High Sensitivity C-reactive Protein</title>
          <description>Mean difference in plasma high sensitivity C-reactive protein level, before and after treatment with simvastatin</description>
          <units>mg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.2" spread="11"/>
                    <measurement group_id="O2" value="2.989" spread="4.169"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.003</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin</title>
        <time_frame>Baseline and 3 months</time_frame>
        <population>change in baseline cholesterol level from baseline, after treatment with simvastatin</population>
        <group_list>
          <group group_id="O1">
            <title>Baseline Cholesterol</title>
            <description>mean cholesterol level (mmol/L) prior to treatment with simvastatin</description>
          </group>
          <group group_id="O2">
            <title>Simvastatin Treatment</title>
            <description>after treatment with simvastatin: 40 mg, orally, once daily for 3 months</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin</title>
          <population>change in baseline cholesterol level from baseline, after treatment with simvastatin</population>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="124" spread="27"/>
                    <measurement group_id="O2" value="101" spread="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Safety data were collected on each participant during the treatment period (3 months) and at 1 month follow up</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Simvastatin</title>
          <description>Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months&#xD;
Simvastatin: 40 mg, orally, once daily for 3 months</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>sickle cell vaso-occlusive pain crisis</sub_title>
                <description>Four participants were hospitalized for sickle cell related vaso-occlusive pain crisis (expected SAE)</description>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>hyperhemolysis</sub_title>
                <description>One participant was hospitalized for sickle cell related hyperhemolytic event (unrelated to study drug)</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>facial rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </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. Carolyn Hoppe</name_or_title>
      <organization>UCSF Benioff Children's Hospital Oakland</organization>
      <phone>(510)428-3193</phone>
      <email>choppe@mail.cho.org</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/NCT01702246
org study id: DDCF-ICRA-2011
nct id: NCT01702246
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine whether simvastatin is effective in reducing the
      frequency and intensity of vaso-occlusive pain episodes in patients with sickle cell disease.
Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive episodes and a chronic
      inflammatory state leading to progressive multi-organ injury. The pathophysiology of SCD is
      related to endothelial dysfunction driven largely by impaired nitric oxide (NO) homeostasis
      and chronic inflammation. Through multiple mechanisms, including upregulation of NO, statins
      have been shown to confer protection from endothelial injury, independent of their
      cholesterol-lowering properties.

      By inhibiting inflammation and several common pathways leading to vascular damage,simvastatin
      may help prevent the acute and chronic complications of SCD. The objective of this study is
      to determine whether our preliminary results showing simvastatin-associated reductions in
      plasma markers of vascular injury will translate into a reduction in vaso-occlusive pain
      episodes in patients with SCD. A web-based, smartphone-accessible electronic pain diary will
      be used to monitor frequency and intensity of vaso-occlusive pain in SCD patients treated
      with a single daily dose of simvastatin.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Frequency of Vaso-occlusive Pain Events, Before and After Treatment With Simvastatin
time frame: Baseline and 3 months
description: The effect of simvastatin treatment will be assessed by measuring the difference from baseline in the mean frequency (and intensity) of vaso-occlusive pain events, after treatment with simvastatin. Pain rate (proportion of pain days) was defined as the number of days reported with sickle cell disease-related pain divided by the number of daily pain diaries completed.
measure: Change in Plasma High Sensitivity C-reactive Protein
time frame: Baseline and 3 months
description: Mean difference in plasma high sensitivity C-reactive protein level, before and after treatment with simvastatin
measure: Change From Baseline in Total Cholesterol Level After Treatment With Simvastatin
time frame: Baseline and 3 months
arm group label: simvastatin
arm group type: Experimental
description: Simvastatin (Zocor), 40mg tablet, 40mg orally once daily, for 3 months
intervention type: Drug
intervention name: Simvastatin
description: 40 mg, orally, once daily for 3 months
arm group label: simvastatin
other name: Zocor
criteria: 
gender: All
minimum age: 10 Years
maximum age: N/A
healthy volunteers: No
last name: Carolyn Hoppe, MD
role: Principal Investigator
affiliation: UCSF Benioff Children's Hospital Oakland
facility: 
country: United States
citation: Hoppe C, Kuypers F, Larkin S, Hagar W, Vichinsky E, Styles L. A pilot study of the short-term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction. Br J Haematol. 2011 Jun;153(5):655-63. doi: 10.1111/j.1365-2141.2010.08480.x. Epub 2011 Apr 8.
PMID: 21477202
responsible party type: Principal Investigator
investigator affiliation: UCSF Benioff Children's Hospital Oakland
investigator full name: Carolyn Hoppe
investigator title: Associate Hematologist-Oncologist
mesh term: Anemia, Sickle Cell
mesh term: Simvastatin
sharing ipd: No
ipd description: publication
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 