<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/NCT01708278</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00061735</org_study_id>
    <secondary_id>R21AT007357</secondary_id>
    <nct_id>NCT01708278</nct_id>
    <nct_alias>NCT02013440</nct_alias>
  </id_info>
  <brief_title>Beneficial Effects of Quercetin in Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <acronym>Quercetin</acronym>
  <official_title>Phase I Study to Determine the Safety of Quercetin in COPD Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Quercegen Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Complementary and Integrative Health (NCCIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chronic obstructive pulmonary disease (COPD) is a progressive disorder of the lung parenchyma&#xD;
      and airways, which is the third-leading cause of death in the USA. Current therapies for COPD&#xD;
      are only partially effective and may also have side effects. Although increasing evidence&#xD;
      indicates that quercetin supplementation may be beneficial in treating COPD, key&#xD;
      methodological issues have not been resolved. The overall objective of this study is to&#xD;
      determine the dosage of quercetin supplementation, bioavailability of quercetin, safety,&#xD;
      dose-response relationship and appropriate biomarkers which reflect clinical outcomes in&#xD;
      patients with COPD that is necessary for conducting large clinical trials in this patient&#xD;
      population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In our preclinical study, we have demonstrated that 4 fold increase in plasma quercetin&#xD;
      levels significantly decreased lung inflammation and prevented progression. Clinical studies&#xD;
      in healthy volunteers 4 fold increase in plasma quercetin levels (0.22 to 1 µM) could be&#xD;
      achieved by supplementing with 500mg of quercetin/day. However, safety of quercetin&#xD;
      supplementation and quercetin dose required to achieve 4 fold increases in plasma quercetin&#xD;
      levels in 'at-high-risk' COPD population is yet to be established. This study involves two&#xD;
      phases; the first phase examines the safety of quercetin supplementation in subjects with&#xD;
      chronic obstructive pulmonary disease (COPD) and the second phase determines the efficacy of&#xD;
      quercetin in COPD patients. In this study, we will enroll COPD patients with mild to moderate&#xD;
      disease between the age group of 40 to 65 years. During the first phase, we will enroll a&#xD;
      total of 9 patients to examine the tolerance and safety of three doses of quercetin (500,&#xD;
      1000 and 2000 mg/day) in a dose escalation manner. First cohort consisting of three subjects&#xD;
      will receive placebo or 500 mg of quercetin per day for one week and the safety of quercetin&#xD;
      supplementation will be assessed by monitoring adverse events and any changes in outcomes of&#xD;
      blood test that include complete blood counts (CBC)and comprehensive metabolic panel prior to&#xD;
      after supplementation. If this dose is safe and tolerated, second cohort of 3 subjects will&#xD;
      receive placebo or 1000 mg of quercetin per day quercetin for one week and again safety will&#xD;
      be assessed. If the dose is safely tolerated, the third cohort will receive either placebo or&#xD;
      2000 mg of quercetin per day for a week and the safety will be assessed.&#xD;
&#xD;
      Having completed Phase I study at University of Michigan, we planned to do the Phase II&#xD;
      efficacy study under separate NCT number. As of 2016 this phase II study has not begun. Based&#xD;
      on the initial study, we plan to choose the highest quercetin dose tolerated with no adverse&#xD;
      events and the dose (500 mg of quercetin per day) that was found to increase plasma quercetin&#xD;
      levels by 4 fold over baseline in healthy volunteers to examine the efficacy of quercetin in&#xD;
      reducing inflammatory and oxidative stress markers and improving lung function in COPD&#xD;
      subjects. In the second phase, we will enroll a total of 75 subjects and randomized into&#xD;
      three arms; placebo (15 subjects) or one of the two doses of quercetin (30 subjects per arm).&#xD;
      All enrolled subjects will be asked to avoid quercetin rich foods throughout the study&#xD;
      period. One week after enrollment (run-in), subjects will be either supplemented with either&#xD;
      placebo or one of the two doses of quercetin for 4 weeks. All participants will be blinded&#xD;
      for study agents. Plasma and sputum quercetin levels, lung function, and markers of oxidative&#xD;
      stress and inflammation will be determined at the start of the study (following run-in&#xD;
      period), at the end of 4 weeks treatment period.&#xD;
&#xD;
      Three of the original outcome measures listed related to this follow up study of 4 weeks&#xD;
      treatment which was never begun. Therefore they have been deleted.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <phase>Phase 1</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Participants Who Experienced Safety Concerns, Where Safety Concerns of Quercetin Supplementation is Indicated by Significant Change From Baseline Measures of Tests Indicated Below in Outcome Measure Description</measure>
    <time_frame>One week in Phase I safety study</time_frame>
    <description>Note: If values for any of the measures indicated here were found, the participant would be indicated as a participant with a safety concern, and values for that particular measure would be posted specifically, but since none of the participants experienced these outlying values, results of all tests are expressed here as a composite function.&#xD;
PULMONARY FUNCTION TEST:&#xD;
FEV1% of predicted: decline by &gt;20% from baseline COMPLETE BLOOD COUNTS: WBC (cells)/mm3 : &lt;2000, Platelets (cells)/mm3: &lt;25,000, Hemoglobin (g/dL): &lt;7.0 COMPREHENSIVE METABOLIC PROFILE (study drug related):Sodium (mmol/L): &lt;125 or &gt;148, Potassium (mmol/L): &lt; 3.0 or &gt; 6.0, Calcium (mmol/L): &lt;7.4 or &gt; 11.5, LIVER FUNCTION TESTS INCREASE BY FACTOR: Enzymes ALT, AST, and Alkaline phosphate, Total bilirubin: for any of these a value &gt;3X upper limit of normal</description>
  </primary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Sugar chew-Cohort 1</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>contains 350 mg of vitamin C and 10 mg niacin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Quercetin 1-Cohort 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Quercetin chew containing 500 mg quercetin, 350 mg vitamin C and 10 mg niacin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Quercetin 2-Cohort 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Quercetin chew containing 1000 mg quercetin, 350 mg vitamin C and 10 mg niacin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Quercetin 3-Cohort 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Quercetin chew containing 2000 mg quercetin, 350 mg vitamin C and 10 mg niacin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar chew-Cohort 2</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>contains 350 mg of vitamin C and 10 mg niacin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar Chew-Cohort 3</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>contains 350 mg of vitamin C and 10 mg niacin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Quercetin</intervention_name>
    <description>COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
    <arm_group_label>Quercetin 1-Cohort 1</arm_group_label>
    <arm_group_label>Quercetin 2-Cohort 2</arm_group_label>
    <arm_group_label>Quercetin 3-Cohort 3</arm_group_label>
    <other_name>QB3C without folic acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo - sugar chew</intervention_name>
    <description>COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
    <arm_group_label>Sugar Chew-Cohort 3</arm_group_label>
    <arm_group_label>Sugar chew-Cohort 1</arm_group_label>
    <arm_group_label>Sugar chew-Cohort 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects diagnosed with mild to moderate COPD (GOLD stage I, II and III)-&#xD;
&#xD;
          -  10 pack-year smoking history or greater and ceased to smoke at least for 2 months&#xD;
             prior to recruitment&#xD;
&#xD;
          -  Subjects taking H2 antagonists, Imodium or loratadine and willing to stop during the&#xD;
             study period&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  COPD subjects with &gt;80% or &lt;35% predicted&#xD;
&#xD;
          -  Current smokers&#xD;
&#xD;
          -  Known allergy/sensitivity to quercetin&#xD;
&#xD;
          -  Subjects with primary diagnosis of asthma&#xD;
&#xD;
          -  Upper respiratory tract infection within two weeks of the screening visit&#xD;
&#xD;
          -  Acute bacterial infection requiring antibiotics within two weeks of screening&#xD;
&#xD;
          -  Emergency treatment or hospitalization within one month of screening&#xD;
&#xD;
          -  Pregnant or lactating mothers&#xD;
&#xD;
          -  Women who don't consent to take pregnancy test&#xD;
&#xD;
          -  Unwillingness to stop flavonoid supplementation&#xD;
&#xD;
          -  Dietary intake exceeding or averaging 150 mg quercetin daily as assessed by&#xD;
             Bioflavonoid Food and Supplement Screener&#xD;
&#xD;
          -  Daily oral steroid treatment, warfarin, cyclosporine (neural, sandimmune), digoxin,&#xD;
             fexofenadine, paclitaxel, diltiazem, saquinavir, selected chemotherapeutic agents&#xD;
             (etoposide, vinblastine, vincristine, vindesine), antifungals (ketoconazole,&#xD;
             itraconazole), protease inhibitors (amprenavir, indinavir, nelfinavir), verapamil,&#xD;
             oral glucocorticoids, erythromycin, quinidine&#xD;
&#xD;
          -  Subjects taking H2 antagonists (cimetidine, ranitidine), loperamide (Imodium) or&#xD;
             loratadine and not willing to stop during study period&#xD;
&#xD;
          -  Lung cancer history or undergoing chemo- or radiation therapy&#xD;
&#xD;
          -  Inflammatory bowel disease&#xD;
&#xD;
          -  Child bearing age, who are unwilling to use adequate contraception or abstain during&#xD;
             the course of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fernando J Martinez, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Ganesan S, Faris AN, Comstock AT, Chattoraj SS, Chattoraj A, Burgess JR, Curtis JL, Martinez FJ, Zick S, Hershenson MB, Sajjan US. Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression. Respir Res. 2010 Sep 28;11(1):131. doi: 10.1186/1465-9921-11-131.</citation>
    <PMID>20920189</PMID>
  </reference>
  <reference>
    <citation>Ganesan S, Faris AN, Comstock AT, Wang Q, Nanua S, Hershenson MB, Sajjan US. Quercetin inhibits rhinovirus replication in vitro and in vivo. Antiviral Res. 2012 Jun;94(3):258-71. doi: 10.1016/j.antiviral.2012.03.005. Epub 2012 Mar 23.</citation>
    <PMID>22465313</PMID>
  </reference>
  <reference>
    <citation>Comstock AT, Ganesan S, Chattoraj A, Faris AN, Margolis BL, Hershenson MB, Sajjan US. Rhinovirus-induced barrier dysfunction in polarized airway epithelial cells is mediated by NADPH oxidase 1. J Virol. 2011 Jul;85(13):6795-808. doi: 10.1128/JVI.02074-10. Epub 2011 Apr 20.</citation>
    <PMID>21507984</PMID>
  </reference>
  <reference>
    <citation>Jin F, Nieman DC, Shanely RA, Knab AM, Austin MD, Sha W. The variable plasma quercetin response to 12-week quercetin supplementation in humans. Eur J Clin Nutr. 2010 Jul;64(7):692-7. doi: 10.1038/ejcn.2010.91. Epub 2010 Jun 2.</citation>
    <PMID>20517329</PMID>
  </reference>
  <reference>
    <citation>Boots AW, Wilms LC, Swennen EL, Kleinjans JC, Bast A, Haenen GR. In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. Nutrition. 2008 Jul-Aug;24(7-8):703-10. doi: 10.1016/j.nut.2008.03.023.</citation>
    <PMID>18549926</PMID>
  </reference>
  <reference>
    <citation>Terao J, Murota K, Kawai Y. Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo. Food Funct. 2011 Jan;2(1):11-7. doi: 10.1039/c0fo00106f. Epub 2010 Nov 17.</citation>
    <PMID>21773581</PMID>
  </reference>
  <reference>
    <citation>Boots AW, Drent M, de Boer VC, Bast A, Haenen GR. Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis. Clin Nutr. 2011 Aug;30(4):506-12. doi: 10.1016/j.clnu.2011.01.010. Epub 2011 Feb 15.</citation>
    <PMID>21324570</PMID>
  </reference>
  <reference>
    <citation>Bischoff SC. Quercetin: potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care. 2008 Nov;11(6):733-40. doi: 10.1097/MCO.0b013e32831394b8.</citation>
    <PMID>18827577</PMID>
  </reference>
  <reference>
    <citation>Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol. 2007 Nov;45(11):2179-205. doi: 10.1016/j.fct.2007.05.015. Epub 2007 Jun 7.</citation>
    <PMID>17698276</PMID>
  </reference>
  <reference>
    <citation>Okamoto T. Safety of quercetin for clinical application (Review). Int J Mol Med. 2005 Aug;16(2):275-8.</citation>
    <PMID>16012761</PMID>
  </reference>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>October 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <results_first_submitted>October 31, 2016</results_first_submitted>
  <results_first_submitted_qc>October 31, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 26, 2016</results_first_posted>
  <last_update_submitted>October 31, 2016</last_update_submitted>
  <last_update_submitted_qc>October 31, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 26, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Umadevi S. Sajjan</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>Emphysema</keyword>
  <keyword>chronic bronchitis</keyword>
  <keyword>Quercetin</keyword>
  <keyword>flavonoids</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Folic Acid</mesh_term>
    <mesh_term>Quercetin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sugar Chew- Cohort 1</title>
          <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
        </group>
        <group group_id="P2">
          <title>Quercetin 1-Cohort 1</title>
          <description>Quercetin chew containing 500 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
        </group>
        <group group_id="P3">
          <title>Quercetin 2-Cohort 2</title>
          <description>Quercetin chew containing 1000 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
        </group>
        <group group_id="P4">
          <title>Quercetin 3-Cohort 3</title>
          <description>Quercetin chew containing 2000 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
        </group>
        <group group_id="P5">
          <title>Sugar Chew-Cohort 2</title>
          <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
        </group>
        <group group_id="P6">
          <title>Sugar Chew-Cohort 3</title>
          <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
              </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="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sugar Chew- Cohort 1</title>
          <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
        </group>
        <group group_id="B2">
          <title>Quercetin 1-Cohort 1</title>
          <description>Quercetin chew containing 500 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
        </group>
        <group group_id="B3">
          <title>Quercetin 2-Cohort 2</title>
          <description>Quercetin chew containing 1000 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
        </group>
        <group group_id="B4">
          <title>Quercetin 3-Cohort 3</title>
          <description>Quercetin chew containing 2000 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
        </group>
        <group group_id="B5">
          <title>Sugar Chew-Cohort 2</title>
          <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
        </group>
        <group group_id="B6">
          <title>Sugar Chew-Cohort 3</title>
          <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</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="1"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="2"/>
            <count group_id="B4" value="2"/>
            <count group_id="B5" value="1"/>
            <count group_id="B6" value="1"/>
            <count group_id="B7" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Age 40 - 80 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="9"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="5"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Lung Function</title>
          <description>Lung Function FEV1 between 35 and 80% predicted</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Participants Who Experienced Safety Concerns, Where Safety Concerns of Quercetin Supplementation is Indicated by Significant Change From Baseline Measures of Tests Indicated Below in Outcome Measure Description</title>
        <description>Note: If values for any of the measures indicated here were found, the participant would be indicated as a participant with a safety concern, and values for that particular measure would be posted specifically, but since none of the participants experienced these outlying values, results of all tests are expressed here as a composite function.&#xD;
PULMONARY FUNCTION TEST:&#xD;
FEV1% of predicted: decline by &gt;20% from baseline COMPLETE BLOOD COUNTS: WBC (cells)/mm3 : &lt;2000, Platelets (cells)/mm3: &lt;25,000, Hemoglobin (g/dL): &lt;7.0 COMPREHENSIVE METABOLIC PROFILE (study drug related):Sodium (mmol/L): &lt;125 or &gt;148, Potassium (mmol/L): &lt; 3.0 or &gt; 6.0, Calcium (mmol/L): &lt;7.4 or &gt; 11.5, LIVER FUNCTION TESTS INCREASE BY FACTOR: Enzymes ALT, AST, and Alkaline phosphate, Total bilirubin: for any of these a value &gt;3X upper limit of normal</description>
        <time_frame>One week in Phase I safety study</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sugar Chew- Cohort 1</title>
            <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
          </group>
          <group group_id="O2">
            <title>Quercetin 1-Cohort 1</title>
            <description>Quercetin chew containing 500 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
          </group>
          <group group_id="O3">
            <title>Quercetin 2-Cohort 2</title>
            <description>Quercetin chew containing 1000 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
          </group>
          <group group_id="O4">
            <title>Quercetin 3-Cohort 3</title>
            <description>Quercetin chew containing 2000 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
          </group>
          <group group_id="O5">
            <title>Sugar Chew-Cohort 2</title>
            <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
          </group>
          <group group_id="O6">
            <title>Sugar Chew-Cohort 3</title>
            <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
          </group>
        </group_list>
        <measure>
          <title>Participants Who Experienced Safety Concerns, Where Safety Concerns of Quercetin Supplementation is Indicated by Significant Change From Baseline Measures of Tests Indicated Below in Outcome Measure Description</title>
          <description>Note: If values for any of the measures indicated here were found, the participant would be indicated as a participant with a safety concern, and values for that particular measure would be posted specifically, but since none of the participants experienced these outlying values, results of all tests are expressed here as a composite function.&#xD;
PULMONARY FUNCTION TEST:&#xD;
FEV1% of predicted: decline by &gt;20% from baseline COMPLETE BLOOD COUNTS: WBC (cells)/mm3 : &lt;2000, Platelets (cells)/mm3: &lt;25,000, Hemoglobin (g/dL): &lt;7.0 COMPREHENSIVE METABOLIC PROFILE (study drug related):Sodium (mmol/L): &lt;125 or &gt;148, Potassium (mmol/L): &lt; 3.0 or &gt; 6.0, Calcium (mmol/L): &lt;7.4 or &gt; 11.5, LIVER FUNCTION TESTS INCREASE BY FACTOR: Enzymes ALT, AST, and Alkaline phosphate, Total bilirubin: for any of these a value &gt;3X upper limit of normal</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="2"/>
                <count group_id="O5" value="1"/>
                <count group_id="O6" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>14 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Sugar Chew-Cohort 1</title>
          <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
        </group>
        <group group_id="E2">
          <title>Quercetin 1-Cohort 1</title>
          <description>Quercetin chew containing 500 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
        </group>
        <group group_id="E3">
          <title>Quercetin 2-Cohort 2</title>
          <description>Quercetin chew containing 1000 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
        </group>
        <group group_id="E4">
          <title>Quercetin 3-Cohort 3</title>
          <description>Quercetin chew containing 2000 mg quercetin, 350 mg vitamin C and 10 mg niacin&#xD;
Quercetin: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week&#xD;
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin&#xD;
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin</description>
        </group>
        <group group_id="E5">
          <title>Sugar Chew-Cohort 2</title>
          <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</description>
        </group>
        <group group_id="E6">
          <title>Sugar Chew-Cohort 3</title>
          <description>contains 350 mg of vitamin C and 10 mg niacin&#xD;
Placebo - sugar chew: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)</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="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
              </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="1"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Heart burn, GERD</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Flu</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>high glucose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>headache/neck pain/low back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Congestion/Breathlessness/chest tightness/cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Fernando Martinez</name_or_title>
      <organization>University of Michigan</organization>
      <phone>(734) 763-2540</phone>
      <email>fmartine@umich.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/NCT01708278
org study id: HUM00061735
secondary id: R21AT007357
nct id: NCT01708278
nct alias: NCT02013440
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Chronic obstructive pulmonary disease (COPD) is a progressive disorder of the lung parenchyma
      and airways, which is the third-leading cause of death in the USA. Current therapies for COPD
      are only partially effective and may also have side effects. Although increasing evidence
      indicates that quercetin supplementation may be beneficial in treating COPD, key
      methodological issues have not been resolved. The overall objective of this study is to
      determine the dosage of quercetin supplementation, bioavailability of quercetin, safety,
      dose-response relationship and appropriate biomarkers which reflect clinical outcomes in
      patients with COPD that is necessary for conducting large clinical trials in this patient
      population.
In our preclinical study, we have demonstrated that 4 fold increase in plasma quercetin
      levels significantly decreased lung inflammation and prevented progression. Clinical studies
      in healthy volunteers 4 fold increase in plasma quercetin levels (0.22 to 1 µM) could be
      achieved by supplementing with 500mg of quercetin/day. However, safety of quercetin
      supplementation and quercetin dose required to achieve 4 fold increases in plasma quercetin
      levels in 'at-high-risk' COPD population is yet to be established. This study involves two
      phases; the first phase examines the safety of quercetin supplementation in subjects with
      chronic obstructive pulmonary disease (COPD) and the second phase determines the efficacy of
      quercetin in COPD patients. In this study, we will enroll COPD patients with mild to moderate
      disease between the age group of 40 to 65 years. During the first phase, we will enroll a
      total of 9 patients to examine the tolerance and safety of three doses of quercetin (500,
      1000 and 2000 mg/day) in a dose escalation manner. First cohort consisting of three subjects
      will receive placebo or 500 mg of quercetin per day for one week and the safety of quercetin
      supplementation will be assessed by monitoring adverse events and any changes in outcomes of
      blood test that include complete blood counts (CBC)and comprehensive metabolic panel prior to
      after supplementation. If this dose is safe and tolerated, second cohort of 3 subjects will
      receive placebo or 1000 mg of quercetin per day quercetin for one week and again safety will
      be assessed. If the dose is safely tolerated, the third cohort will receive either placebo or
      2000 mg of quercetin per day for a week and the safety will be assessed.

      Having completed Phase I study at University of Michigan, we planned to do the Phase II
      efficacy study under separate NCT number. As of 2016 this phase II study has not begun. Based
      on the initial study, we plan to choose the highest quercetin dose tolerated with no adverse
      events and the dose (500 mg of quercetin per day) that was found to increase plasma quercetin
      levels by 4 fold over baseline in healthy volunteers to examine the efficacy of quercetin in
      reducing inflammatory and oxidative stress markers and improving lung function in COPD
      subjects. In the second phase, we will enroll a total of 75 subjects and randomized into
      three arms; placebo (15 subjects) or one of the two doses of quercetin (30 subjects per arm).
      All enrolled subjects will be asked to avoid quercetin rich foods throughout the study
      period. One week after enrollment (run-in), subjects will be either supplemented with either
      placebo or one of the two doses of quercetin for 4 weeks. All participants will be blinded
      for study agents. Plasma and sputum quercetin levels, lung function, and markers of oxidative
      stress and inflammation will be determined at the start of the study (following run-in
      period), at the end of 4 weeks treatment period.

      Three of the original outcome measures listed related to this follow up study of 4 weeks
      treatment which was never begun. Therefore they have been deleted.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Participants Who Experienced Safety Concerns, Where Safety Concerns of Quercetin Supplementation is Indicated by Significant Change From Baseline Measures of Tests Indicated Below in Outcome Measure Description
time frame: One week in Phase I safety study
description: Note: If values for any of the measures indicated here were found, the participant would be indicated as a participant with a safety concern, and values for that particular measure would be posted specifically, but since none of the participants experienced these outlying values, results of all tests are expressed here as a composite function.
PULMONARY FUNCTION TEST:
FEV1% of predicted: decline by >20% from baseline COMPLETE BLOOD COUNTS: WBC (cells)/mm3 : <2000, Platelets (cells)/mm3: <25,000, Hemoglobin (g/dL): <7.0 COMPREHENSIVE METABOLIC PROFILE (study drug related):Sodium (mmol/L): <125 or >148, Potassium (mmol/L): < 3.0 or > 6.0, Calcium (mmol/L): <7.4 or > 11.5, LIVER FUNCTION TESTS INCREASE BY FACTOR: Enzymes ALT, AST, and Alkaline phosphate, Total bilirubin: for any of these a value >3X upper limit of normal
arm group label: Sugar chew-Cohort 1
arm group type: Placebo Comparator
description: contains 350 mg of vitamin C and 10 mg niacin
arm group label: Quercetin 1-Cohort 1
arm group type: Active Comparator
description: Quercetin chew containing 500 mg quercetin, 350 mg vitamin C and 10 mg niacin
arm group label: Quercetin 2-Cohort 2
arm group type: Active Comparator
description: Quercetin chew containing 1000 mg quercetin, 350 mg vitamin C and 10 mg niacin
arm group label: Quercetin 3-Cohort 3
arm group type: Active Comparator
description: Quercetin chew containing 2000 mg quercetin, 350 mg vitamin C and 10 mg niacin
arm group label: Sugar chew-Cohort 2
arm group type: Placebo Comparator
description: contains 350 mg of vitamin C and 10 mg niacin
arm group label: Sugar Chew-Cohort 3
arm group type: Placebo Comparator
description: contains 350 mg of vitamin C and 10 mg niacin
intervention type: Drug
intervention name: Quercetin
description: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week
Quercetin 500 mg/350 mg of vitamin C and 10 mg niacin
Quercetin 1000 mg/350 mg of vitamin C and 10 mg niacin
Quercetin 2000 mg/350 mg of vitamin C and 10 mg niacin
arm group label: Quercetin 1-Cohort 1
arm group label: Quercetin 2-Cohort 2
arm group label: Quercetin 3-Cohort 3
other name: QB3C without folic acid
intervention type: Other
intervention name: Placebo - sugar chew
description: COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo (sugar chew containing 350 mg of vitamin C and 10 mg niacin)
arm group label: Sugar Chew-Cohort 3
arm group label: Sugar chew-Cohort 1
arm group label: Sugar chew-Cohort 2
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Fernando J Martinez, M.D.
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
citation: Ganesan S, Faris AN, Comstock AT, Chattoraj SS, Chattoraj A, Burgess JR, Curtis JL, Martinez FJ, Zick S, Hershenson MB, Sajjan US. Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression. Respir Res. 2010 Sep 28;11(1):131. doi: 10.1186/1465-9921-11-131.
PMID: 20920189
citation: Ganesan S, Faris AN, Comstock AT, Wang Q, Nanua S, Hershenson MB, Sajjan US. Quercetin inhibits rhinovirus replication in vitro and in vivo. Antiviral Res. 2012 Jun;94(3):258-71. doi: 10.1016/j.antiviral.2012.03.005. Epub 2012 Mar 23.
PMID: 22465313
citation: Comstock AT, Ganesan S, Chattoraj A, Faris AN, Margolis BL, Hershenson MB, Sajjan US. Rhinovirus-induced barrier dysfunction in polarized airway epithelial cells is mediated by NADPH oxidase 1. J Virol. 2011 Jul;85(13):6795-808. doi: 10.1128/JVI.02074-10. Epub 2011 Apr 20.
PMID: 21507984
citation: Jin F, Nieman DC, Shanely RA, Knab AM, Austin MD, Sha W. The variable plasma quercetin response to 12-week quercetin supplementation in humans. Eur J Clin Nutr. 2010 Jul;64(7):692-7. doi: 10.1038/ejcn.2010.91. Epub 2010 Jun 2.
PMID: 20517329
citation: Boots AW, Wilms LC, Swennen EL, Kleinjans JC, Bast A, Haenen GR. In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. Nutrition. 2008 Jul-Aug;24(7-8):703-10. doi: 10.1016/j.nut.2008.03.023.
PMID: 18549926
citation: Terao J, Murota K, Kawai Y. Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo. Food Funct. 2011 Jan;2(1):11-7. doi: 10.1039/c0fo00106f. Epub 2010 Nov 17.
PMID: 21773581
citation: Boots AW, Drent M, de Boer VC, Bast A, Haenen GR. Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis. Clin Nutr. 2011 Aug;30(4):506-12. doi: 10.1016/j.clnu.2011.01.010. Epub 2011 Feb 15.
PMID: 21324570
citation: Bischoff SC. Quercetin: potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care. 2008 Nov;11(6):733-40. doi: 10.1097/MCO.0b013e32831394b8.
PMID: 18827577
citation: Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol. 2007 Nov;45(11):2179-205. doi: 10.1016/j.fct.2007.05.015. Epub 2007 Jun 7.
PMID: 17698276
citation: Okamoto T. Safety of quercetin for clinical application (Review). Int J Mol Med. 2005 Aug;16(2):275-8.
PMID: 16012761
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Umadevi S. Sajjan
investigator title: Assistant Professor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Folic Acid
mesh term: Quercetin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 