<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/NCT01722669</url>
  </required_header>
  <id_info>
    <org_study_id>2012P000022</org_study_id>
    <nct_id>NCT01722669</nct_id>
  </id_info>
  <brief_title>Quercetin PK/PD Study in Healthy Adults and Patients With Hypercoagulable States</brief_title>
  <acronym>PK/PD</acronym>
  <official_title>Pharmacokinetic and Pharmacodynamic Study of Oral Quercetin and Isoquercetin in Healthy Adults and Patients With Hypercoagulable States.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beth Israel Deaconess Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beth Israel Deaconess Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study is to evaluate how much quercetin or isoquercetin is absorbed after a&#xD;
      single dose and evaluate for pharmacokinetic inhibition of protein disulfide isomerase.&#xD;
      Pharmacodynamic studies will also be performed in an additional cohort of 10 patients with&#xD;
      evidence of antiphospholipid antibodies&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To compare the absorption and activity of quercetin or isoquercetin with or without ascorbic&#xD;
      acid in healthy adults. Oral chews containing quercetin (500mg) or isoquercetin(500 mg total)&#xD;
      with or without ascorbic acid will be given. Pharmacokinetic parameters (AUC, Cmax, Tmax,&#xD;
      elimination half-life) will be determined over 24 hours (8 time points). Pharmacodynamic&#xD;
      inhibition of protein disulfide isomerase activity will also be assessed.&#xD;
&#xD;
      In addition to healthy subjects, a cohort of 10 individuals with antiphospholipid antibodies&#xD;
      will participate. These participants will receive isoquercetin 1000 mg and have&#xD;
      pharmacodynamics studies performed at time 0 and 4 hours.&#xD;
&#xD;
      All study drugs will be provided by Quercegen Pharma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2012</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC</measure>
    <time_frame>24 hours</time_frame>
    <description>AUC 0-24 hours of measured plasma quercetin aglycone for Arms A1, B1, A2, B2, C Collected at timepoints: baseline and 1, 2, 4, 6, 8, and 24 hours after dose. PK and PDI samples were not measured for Arm D (anti-phospholipid antibody cohort)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reductase Activity of PDI Using Dieosin Glutathione Disulfide</measure>
    <time_frame>2 hours. Not measured in D</time_frame>
    <description>Measurement of protein disulfide inhibition in plasma using a fluorescent PDI substrate (dieosin glutathione disulfide)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet-induced Thrombin Generation (U/mL)</measure>
    <time_frame>4 hours</time_frame>
    <description>Thrombin induced thrombin generation measured in patient plasma</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Quercetin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of quercetin with or without ascorbic acid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Isoquercetin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Single dose of isoquercetin with or without ascorbic acid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>isoquercetin or quercetin</intervention_name>
    <description>Single dose PK/PD study</description>
    <arm_group_label>Isoquercetin</arm_group_label>
    <arm_group_label>Quercetin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Subject is willing to participate and provide informed consent&#xD;
&#xD;
          -  Subject is considered reliable and capable of adhering to the protocol per the&#xD;
             judgment of the Investigator&#xD;
&#xD;
          -  Subjects in group D must exhibit good organ reserves (within prior 4 weeks) defined&#xD;
             as:&#xD;
&#xD;
               1. Estimated GFR &gt;35 (formula),&#xD;
&#xD;
               2. Platelet count &gt;65 K/uL,&#xD;
&#xD;
               3. Hemoglobin &gt;10.5 grams/dL&#xD;
&#xD;
               4. Total bilirubin &lt;2.0 mg/dL&#xD;
&#xD;
          -  Minimum age 18 years old&#xD;
&#xD;
          -  Body mass index (BMI) between 18 and 35 kg/m2&#xD;
&#xD;
          -  For cohort D (antiphospholipid antibodies) a. Subjects in group D must have at least&#xD;
             one positive antiphospholipid antibody within the last 8 weeks and/or previous&#xD;
             confirmed antibodies (2 or more occasions at least 12 weeks apart) : i. Positive lupus&#xD;
             anticoagulant ii. anticardiolipin antibody IgM or IgG (&gt;40U GPL) iii. anti-β2&#xD;
             Glycoprotein1 antibody titer (&gt;35 units)&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Pregnant. If female of child-bearing age, negative urinary pregnancy test prior to&#xD;
             dosing of quercetin or isoquercetin&#xD;
&#xD;
          -  No history of malabsorptive gastrointestinal disorder&#xD;
&#xD;
          -  Currently taking aspirin, NSAIDS, warfarin, low-molecular weight heparin or other&#xD;
             anticoagulants (such as direct thrombin inhibitors or factor X inhibitors)&#xD;
&#xD;
             a. Note: Study subjects taking aspirin or NSAIDS, if treating physician concurs, are&#xD;
             permitted to enroll if plan to hold for aspirin 10 days or NSAIDS 24 hours prior to&#xD;
             dosing of quercetin/isoquercetin&#xD;
&#xD;
          -  Prescribed niacin for hyperlipidemia&#xD;
&#xD;
          -  Known HIV&#xD;
&#xD;
          -  History of sensitivity or intolerance to flavonoids, niacin or ascorbic acid&#xD;
&#xD;
          -  May not have uncontrolled intercurrent illness including, but not limited to ongoing&#xD;
             or active infection, hepatitis, symptomatic congestive heart failure, unstable angina&#xD;
             pectoris or cardiac arrhythmia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey Zwicker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beth Israel Deaconess Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>May 10, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 7, 2012</study_first_posted>
  <results_first_submitted>April 6, 2020</results_first_submitted>
  <results_first_submitted_qc>October 9, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 12, 2020</results_first_posted>
  <last_update_submitted>October 9, 2020</last_update_submitted>
  <last_update_submitted_qc>October 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beth Israel Deaconess Medical Center</investigator_affiliation>
    <investigator_full_name>Jeff Zwicker</investigator_full_name>
    <investigator_title>Associate Professor, Harvard Medical School</investigator_title>
  </responsible_party>
  <keyword>quercetin</keyword>
  <keyword>isoquercetin</keyword>
  <keyword>pharmacokinetic</keyword>
  <keyword>pharmacodynamic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombophilia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Quercetin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Contact PI</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>3 years</ipd_time_frame>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 26, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT01722669/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Quercetin 500mg (ARM A1)</title>
          <description>Single dose PK/PD analyses of quercetin 500 mg</description>
        </group>
        <group group_id="P2">
          <title>Isoquercetin 500mg (ARM B1)</title>
          <description>Single dose PK/PD of isoquercetin 500 mg</description>
        </group>
        <group group_id="P3">
          <title>Quercetin 500 mg + Ascorbic Acid (ARM A2)</title>
          <description>Single dose quercetin with 500 mg + ascorbic acid pk/pd analyses</description>
        </group>
        <group group_id="P4">
          <title>Isoquercetin 500 mg + Ascorbic Acid (ARM B2)</title>
          <description>Single dose isoquercetin 500 mg + ascorbic acid pk/pd analyses</description>
        </group>
        <group group_id="P5">
          <title>Isoquercetin 1000 mg + Ascorbic Acid (ARM C)</title>
          <description>Single dose isoquercetin + 1000 mg ascorbic acid</description>
        </group>
        <group group_id="P6">
          <title>Antiphospholipid Antibody Cohort (ARM D)</title>
          <description>Single dose isoquercetin 1000 mg + 1000 mg ascorbic acid in patients with antiphospholipid antibodies</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="8">Antiphospholipid Antibody (ARM D): 6 evaluable and 2 withdrew consent without any data collected</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" 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="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Measure Analysis Population Description: Antiphospholipid Antibody (ARM D): 2 withdrew consent without any data collected</population>
      <group_list>
        <group group_id="B1">
          <title>Quercetin 500 mg (ARM A1)</title>
          <description>Single dose of quercetin PK/PD analysis</description>
        </group>
        <group group_id="B2">
          <title>Isoquercetin 500 mg (ARM B1)</title>
          <description>Single dose of isoquercetin PK/PD analysis</description>
        </group>
        <group group_id="B3">
          <title>Quercetin 500 mg + Ascorbic Acid (ARM A2)</title>
          <description>Single dose of quercetin + ascorbic acid PK/PD analysis</description>
        </group>
        <group group_id="B4">
          <title>Isoquercetin 500 mg + Ascorbic Acid (ARM B2)</title>
          <description>Single dose of isqouercetin +ascorbic acid PK/PD analysis</description>
        </group>
        <group group_id="B5">
          <title>Isoquercetin 1000 mg + Ascorbic Acid (ARM C)</title>
          <description>single dose isoquercetin + ascorbic acid PK/PD analyses</description>
        </group>
        <group group_id="B6">
          <title>Antiphospholipid Antibody (ARM D)</title>
          <description>single dose isoquercetin +ascorbic acid in patients with antiphospholipid antibodies</description>
        </group>
        <group group_id="B7">
          <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="5"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="5"/>
            <count group_id="B5" value="10"/>
            <count group_id="B6" value="6"/>
            <count group_id="B7" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>Antiphospholipid Antibody (ARM D): 2 withdrew consent without data collected</population>
          <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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="4"/>
                    <measurement group_id="B7" value="34"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>Antiphospholipid Antibody (ARM D): 2 withdrew consent without data collected</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <population>Antiphospholipid Antibody (ARM D): 2 withdrew consent without data collected</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>Antiphospholipid Antibody (ARM D): 2 withdrew consent without data collected</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="5"/>
                    <measurement group_id="B7" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AUC</title>
        <description>AUC 0-24 hours of measured plasma quercetin aglycone for Arms A1, B1, A2, B2, C Collected at timepoints: baseline and 1, 2, 4, 6, 8, and 24 hours after dose. PK and PDI samples were not measured for Arm D (anti-phospholipid antibody cohort)</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Quercetin 500 mg (ARM A1)</title>
            <description>Single dose, measurement of plasma quercetin aglycone</description>
          </group>
          <group group_id="O2">
            <title>Isoquercetin 500 mg (ARM B1)</title>
            <description>Single dose, measurement of plasma quercetin aglycone</description>
          </group>
          <group group_id="O3">
            <title>Quercetin 500 mg + Ascorbic Acid (ARM A2)</title>
            <description>Single dose, measurement of plasma quercetin aglycone</description>
          </group>
          <group group_id="O4">
            <title>Isoquercetin 500 mg + Ascorbic Acid (ARM B2)</title>
            <description>Single dose, measurement of plasma quercetin aglycone</description>
          </group>
          <group group_id="O5">
            <title>Isoquercetin 1000 mg + Ascorbic Acid (ARM C)</title>
            <description>Single dose, measurement of plasma quercetin aglycone</description>
          </group>
        </group_list>
        <measure>
          <title>AUC</title>
          <description>AUC 0-24 hours of measured plasma quercetin aglycone for Arms A1, B1, A2, B2, C Collected at timepoints: baseline and 1, 2, 4, 6, 8, and 24 hours after dose. PK and PDI samples were not measured for Arm D (anti-phospholipid antibody cohort)</description>
          <units>uM hr/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="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.78" spread="1.67"/>
                    <measurement group_id="O2" value="15.00" spread="8.94"/>
                    <measurement group_id="O3" value="5.41" spread="2.13"/>
                    <measurement group_id="O4" value="16.34" spread="10.08"/>
                    <measurement group_id="O5" value="40.3" spread="17.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Reductase Activity of PDI Using Dieosin Glutathione Disulfide</title>
        <description>Measurement of protein disulfide inhibition in plasma using a fluorescent PDI substrate (dieosin glutathione disulfide)</description>
        <time_frame>2 hours. Not measured in D</time_frame>
        <population>2 hours after oral ingestion</population>
        <group_list>
          <group group_id="O1">
            <title>Quercetin 500 mg (ARM A1)</title>
            <description>PDI activity measured by DiESSG assay at 0 and 2 hours</description>
          </group>
          <group group_id="O2">
            <title>Isoquercetin 500 mg (ARM B1)</title>
            <description>PDI activity measured by DiESSG assay at 0 and 2 hours</description>
          </group>
          <group group_id="O3">
            <title>Quercetin 500 mg + Ascorbic Acid (ARM A2)</title>
            <description>PDI activity measured by DiESSG assay at 0 and 2 hours</description>
          </group>
          <group group_id="O4">
            <title>Isoquercetin 500 mg + Ascorbic Acid (ARM B2)</title>
            <description>PDI activity measured by DiESSG assay at 0 and 2 hours</description>
          </group>
          <group group_id="O5">
            <title>Isoquercetin 1000 mg + Ascorbic Acid (ARM C)</title>
            <description>PDI activity measured by DiESSG assay at 0 and 2 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Reductase Activity of PDI Using Dieosin Glutathione Disulfide</title>
          <description>Measurement of protein disulfide inhibition in plasma using a fluorescent PDI substrate (dieosin glutathione disulfide)</description>
          <population>2 hours after oral ingestion</population>
          <units>Percent inhibition</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.9" spread="24.14"/>
                    <measurement group_id="O2" value="63.2" spread="25.3"/>
                    <measurement group_id="O3" value="16" spread="31.8"/>
                    <measurement group_id="O4" value="8.3" spread="15.03"/>
                    <measurement group_id="O5" value="38" spread="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Platelet-induced Thrombin Generation (U/mL)</title>
        <description>Thrombin induced thrombin generation measured in patient plasma</description>
        <time_frame>4 hours</time_frame>
        <population>4 hours after single dose only measured in Arm C and Arm D</population>
        <group_list>
          <group group_id="O1">
            <title>Isoquercetin 1000 mg + Ascorbic Acid (ARM C)</title>
            <description>Thrombin induced thrombin generation measured before and after isoquercetin + Ascorbic acid at time 0 and 4 hours</description>
          </group>
          <group group_id="O2">
            <title>Antiphospholipid Antibody (ARM D)</title>
            <description>Thrombin induced thrombin generation measured at time 0 and 4 hours following isoquercetin 1000 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Platelet-induced Thrombin Generation (U/mL)</title>
          <description>Thrombin induced thrombin generation measured in patient plasma</description>
          <population>4 hours after single dose only measured in Arm C and Arm D</population>
          <units>U/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="10"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.30" spread=".28"/>
                    <measurement group_id="O2" value="1.40" spread="2.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Assessed during visit 1, up to 24 hours</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Quercetin 500 mg (ARM A1)</title>
          <description>Toxicity over 24 hours following single dose</description>
        </group>
        <group group_id="E2">
          <title>Isoquercetin 500 mg (ARM B1)</title>
          <description>Toxicity over 24 hours following single dose</description>
        </group>
        <group group_id="E3">
          <title>Quercetin 500 mg + Ascorbic Acid (ARM A2)</title>
          <description>Toxicity over 24 hours following single dose of combined quercetin and ascorbic acid</description>
        </group>
        <group group_id="E4">
          <title>Isoquercetin 500 mg + Ascorbic Acid (ARM B2)</title>
          <description>Toxicity over 24 hours following single dose of combined isoquercetin and ascorbic acid</description>
        </group>
        <group group_id="E5">
          <title>Isoquercetin 1000 mg + Ascorbic Acid (ARM C)</title>
          <description>Toxicity over 24 hours following single dose of isoquercetin</description>
        </group>
        <group group_id="E6">
          <title>Antiphospholipid Antibody (ARM D)</title>
          <description>Toxicity over 24 hours following single dose of isoquercetin</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
              </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="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="6"/>
              </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>Jeffrey Zwicker, Division of Thrombosis and Haemostasis, Division of Hematology and Oncology</name_or_title>
      <organization>Beth Israel Deaconess Medical Center, Harvard Medical School</organization>
      <phone>617-667-9299</phone>
      <email>jzwicker@bidmc.harvard.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/NCT01722669
org study id: 2012P000022
nct id: NCT01722669
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The goal of this study is to evaluate how much quercetin or isoquercetin is absorbed after a
      single dose and evaluate for pharmacokinetic inhibition of protein disulfide isomerase.
      Pharmacodynamic studies will also be performed in an additional cohort of 10 patients with
      evidence of antiphospholipid antibodies
To compare the absorption and activity of quercetin or isoquercetin with or without ascorbic
      acid in healthy adults. Oral chews containing quercetin (500mg) or isoquercetin(500 mg total)
      with or without ascorbic acid will be given. Pharmacokinetic parameters (AUC, Cmax, Tmax,
      elimination half-life) will be determined over 24 hours (8 time points). Pharmacodynamic
      inhibition of protein disulfide isomerase activity will also be assessed.

      In addition to healthy subjects, a cohort of 10 individuals with antiphospholipid antibodies
      will participate. These participants will receive isoquercetin 1000 mg and have
      pharmacodynamics studies performed at time 0 and 4 hours.

      All study drugs will be provided by Quercegen Pharma.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: AUC
time frame: 24 hours
description: AUC 0-24 hours of measured plasma quercetin aglycone for Arms A1, B1, A2, B2, C Collected at timepoints: baseline and 1, 2, 4, 6, 8, and 24 hours after dose. PK and PDI samples were not measured for Arm D (anti-phospholipid antibody cohort)
measure: Reductase Activity of PDI Using Dieosin Glutathione Disulfide
time frame: 2 hours. Not measured in D
description: Measurement of protein disulfide inhibition in plasma using a fluorescent PDI substrate (dieosin glutathione disulfide)
measure: Platelet-induced Thrombin Generation (U/mL)
time frame: 4 hours
description: Thrombin induced thrombin generation measured in patient plasma
arm group label: Quercetin
arm group type: Experimental
description: Single dose of quercetin with or without ascorbic acid
arm group label: Isoquercetin
arm group type: Active Comparator
description: Single dose of isoquercetin with or without ascorbic acid
intervention type: Drug
intervention name: isoquercetin or quercetin
description: Single dose PK/PD study
arm group label: Isoquercetin
arm group label: Quercetin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jeffrey Zwicker, MD
role: Principal Investigator
affiliation: Beth Israel Deaconess Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Beth Israel Deaconess Medical Center
investigator full name: Jeff Zwicker
investigator title: Associate Professor, Harvard Medical School
mesh term: Thrombophilia
mesh term: Quercetin
sharing ipd: Yes
ipd description: Contact PI
ipd info type: Study Protocol
ipd time frame: 3 years
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 