xml: <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/NCT06003270</url>
    </required_header>
    <id_info>
      <org_study_id>20190727</org_study_id>
      <nct_id>NCT06003270</nct_id>
    </id_info>
    <brief_title>Biological Effects of Quercetin in COPD Phase II</brief_title>
    <acronym>polyphenols</acronym>
    <official_title>Effects of Quercetin on the Oxidative Stress and Inflammatory Markers in COPD Phase II</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Temple University</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>Temple University</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>
        This study determines whether quercetin supplementation reduces the inflammation and&#xD;
        oxidative stress markers in patients with chronic obstructive pulmonary disease. It is small&#xD;
        study with 8 subjects receiving quercetin 1000 mg/day, 8 patients receiving 500 mg/day and 4&#xD;
        subjects receive placebo.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder and affects&#xD;
        millions of people globally. Although the exact mechanisms of pathogenesis of this disease&#xD;
        are not well-understood, the general consensus is that oxidative stress and inflammation&#xD;
        induced by exposure to cigarette smoke or other environmental or occupational hazards are&#xD;
        responsible for development of COPD. Therefore, therapies aimed at decreasing oxidative&#xD;
        stress and inflammation constitutes an important component of treating COPD.&#xD;
  &#xD;
        The current pharmacological therapies may provide temporary symptom relief, reduce acute&#xD;
        exacerbations and hospitalizations, but are associated with side effects. Therefore&#xD;
        complementary method of treatment with potentially fewer side effects and relatively&#xD;
        well-tolerated provide promising alternative. One such compound is quercetin, which is plant&#xD;
        polyphenol and is present in variety of foods that we consume. Quercetin has potent&#xD;
        antioxidant and anti-inflammatory properties and reduces oxidative stress and inflammation in&#xD;
        a preclinical model of COPD. Quercetin exerts it antioxidant properties not only by&#xD;
        neutralizing free radical species, but also by enhancing the expression of antioxidant&#xD;
        enzymes. Similarly, quercetin inhibits various protein and lipid kinases by competing for&#xD;
        adenosine triphosphate (ATP) binding sites thus reducing the inflammatory pathways.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">July 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">February 15, 2025</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Double blinded placebo controlled study</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Randomization codes will be generated by a study statistician at the begnnining of the study and is provided to research pharmacist who will be dispensing the study drugs. The study drug bottles will be numbered with no information about the study drug. The randomization codes will not be revealed until all the data is collected and analyzed. Both placebo and quercetin will be similarly packaged and will have similar color, taste and texture.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Oxidative stress markers</measure>
      <time_frame>six months</time_frame>
      <description>8-isoprostane</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Inflammatory markers</measure>
      <time_frame>six months</time_frame>
      <description>Interleukin (IL)-1beta, IL-8, in bronchoalveolar lavage and C-reactive protein (CRP) and surfactant protein (SP)-D in serum</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Quercetin</measure>
      <time_frame>six months</time_frame>
      <description>Levels of quercetin in blood and lung</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Chronic Obstructive Pulmonary Disease</condition>
    <arm_group>
      <arm_group_label>Quercetin 1000 mg/day</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Quercetin 1000 mg/day Quercetin is provided as caplet and each caplet will have 500 mg of quercetin Quercetin will be administered orally twice daily, one half dose (1 caplet) in the morning after breakfast and one half dose (1 caplet) in the evening after dinner for six months.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Quercetin 500mg/day</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Quercetin 500 mg/day Quercetin is provided as caplet and each caplet will have 500 mg of quercetin Quercetin will be administered orally once daily, (1 caplet) in the morning after breakfast and matching placebo in the evening after dinner for six months.&#xD;
  The placebo is added to match the number of caplets with 1000 mg/day arm</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo is also provided as caplets that is similar to quercetin in color, taste and texture and will contain all the stabilizers and the inactive ingredients that is present in the quercetin chews.&#xD;
  Placebo will be administered orally twice daily, one half dose (1caplet) in the morning after breakfast and one half dose (1 caplet) in the evening after dinner for six months.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Quercetin</intervention_name>
      <description>Placebo</description>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_label>Quercetin 1000 mg/day</arm_group_label>
      <arm_group_label>Quercetin 500mg/day</arm_group_label>
      <other_name>Placebo</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Subjects with COPD, 40 - 80 yrs of age&#xD;
  &#xD;
            -  Post-bronchodilator forced expiratory volume (FEV)1/forced vital capacity (FVC) ratio&#xD;
               0.7, FEV1% predicted between 40 to 70&#xD;
  &#xD;
            -  Both active and ex-smokers with at least 10 pack-years history of smoking&#xD;
  &#xD;
            -  COPD patients taking H2 antagonists, loperamide or loratadine and willing to stop&#xD;
               during the study period&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Known allergy/sensitivity to quercetin&#xD;
  &#xD;
            -  Subjects with primary current 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 for any reasons&#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 warfarin or cyclosporine (Neoral, Sandimmune)&#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;
            -  Subjects with no detectable levels of inflammatory CRP or SP-D in blood and/or IL-&#xD;
  &#xD;
               1β or 8-isoprostane in the exhaled breath condensate&#xD;
  &#xD;
            -  Women of child-bearing age and unwilling to take pregnancy test&#xD;
  &#xD;
            -  Child-bearing age, who are unwilling to use adequate contraception or abstain during&#xD;
               the course of the study.&#xD;
  &#xD;
            -  Pregnant or lactating mothers&#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>Nathaniel Marchetti</last_name>
      <role>Principal Investigator</role>
      <affiliation>Temple University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Umadevi Sajjan</last_name>
      <phone>2157077139</phone>
      <email>uma.sajjan@temple.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Nathaniel Marchetti</name>
        <address>
          <city>Philadelphia</city>
          <state>Pennsylvania</state>
          <zip>19140</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>NATHANIEL MARCHETTI, D.O.</last_name>
        <phone>215-707-9929</phone>
        <email>nathaniel.marchetti@tuhs.temple.edu</email>
      </contact>
      <contact_backup>
        <last_name>Umadevi Sajjan, Ph.D</last_name>
        <phone>2157077139</phone>
        <email>uma.sajjan@temple.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Nathaniel Marchetti, D.O</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Umadevi Sajjan, Ph.D.</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>http://clinicaltrials.gov/ct2/show/NCT01708278</url>
      <description>Phase I clinical trials to determine the safety of quercetin supplementation in COPD</description>
    </link>
    <link>
      <url>http://clinicaltrials.gov/ct2/show/NCT03989271</url>
      <description>Biological Effects of Quercetin in COPD</description>
    </link>
    <results_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>
    </results_reference>
    <results_reference>
      <citation>Farazuddin M, Mishra R, Jing Y, Srivastava V, Comstock AT, Sajjan US. Quercetin prevents rhinovirus-induced progression of lung disease in mice with COPD phenotype. PLoS One. 2018 Jul 5;13(7):e0199612. doi: 10.1371/journal.pone.0199612. eCollection 2018.</citation>
      <PMID>29975735</PMID>
    </results_reference>
    <results_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>
    </results_reference>
    <results_reference>
      <citation>Han MK, Barreto TA, Martinez FJ, Comstock AT, Sajjan US. Randomised clinical trial to determine the safety of quercetin supplementation in patients with chronic obstructive pulmonary disease. BMJ Open Respir Res. 2020 Feb;7(1):e000392. doi: 10.1136/bmjresp-2018-000392.</citation>
      <PMID>32071149</PMID>
    </results_reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Temple University</investigator_affiliation>
      <investigator_full_name>Umadevi Sajjan</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <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>Quercetin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06003270
  org study id: 20190727
  nct id: NCT06003270
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This study determines whether quercetin supplementation reduces the inflammation and
        oxidative stress markers in patients with chronic obstructive pulmonary disease. It is small
        study with 8 subjects receiving quercetin 1000 mg/day, 8 patients receiving 500 mg/day and 4
        subjects receive placebo.
  Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder and affects
        millions of people globally. Although the exact mechanisms of pathogenesis of this disease
        are not well-understood, the general consensus is that oxidative stress and inflammation
        induced by exposure to cigarette smoke or other environmental or occupational hazards are
        responsible for development of COPD. Therefore, therapies aimed at decreasing oxidative
        stress and inflammation constitutes an important component of treating COPD.
  
        The current pharmacological therapies may provide temporary symptom relief, reduce acute
        exacerbations and hospitalizations, but are associated with side effects. Therefore
        complementary method of treatment with potentially fewer side effects and relatively
        well-tolerated provide promising alternative. One such compound is quercetin, which is plant
        polyphenol and is present in variety of foods that we consume. Quercetin has potent
        antioxidant and anti-inflammatory properties and reduces oxidative stress and inflammation in
        a preclinical model of COPD. Quercetin exerts it antioxidant properties not only by
        neutralizing free radical species, but also by enhancing the expression of antioxidant
        enzymes. Similarly, quercetin inhibits various protein and lipid kinases by competing for
        adenosine triphosphate (ATP) binding sites thus reducing the inflammatory pathways.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Double blinded placebo controlled study
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Randomization codes will be generated by a study statistician at the begnnining of the study and is provided to research pharmacist who will be dispensing the study drugs. The study drug bottles will be numbered with no information about the study drug. The randomization codes will not be revealed until all the data is collected and analyzed. Both placebo and quercetin will be similarly packaged and will have similar color, taste and texture.
  measure: Oxidative stress markers
  time frame: six months
  description: 8-isoprostane
  measure: Inflammatory markers
  time frame: six months
  description: Interleukin (IL)-1beta, IL-8, in bronchoalveolar lavage and C-reactive protein (CRP) and surfactant protein (SP)-D in serum
  measure: Quercetin
  time frame: six months
  description: Levels of quercetin in blood and lung
  arm group label: Quercetin 1000 mg/day
  arm group type: Active Comparator
  description: Quercetin 1000 mg/day Quercetin is provided as caplet and each caplet will have 500 mg of quercetin Quercetin will be administered orally twice daily, one half dose (1 caplet) in the morning after breakfast and one half dose (1 caplet) in the evening after dinner for six months.
  arm group label: Quercetin 500mg/day
  arm group type: Active Comparator
  description: Quercetin 500 mg/day Quercetin is provided as caplet and each caplet will have 500 mg of quercetin Quercetin will be administered orally once daily, (1 caplet) in the morning after breakfast and matching placebo in the evening after dinner for six months.
  The placebo is added to match the number of caplets with 1000 mg/day arm
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Placebo is also provided as caplets that is similar to quercetin in color, taste and texture and will contain all the stabilizers and the inactive ingredients that is present in the quercetin chews.
  Placebo will be administered orally twice daily, one half dose (1caplet) in the morning after breakfast and one half dose (1 caplet) in the evening after dinner for six months.
  intervention type: Drug
  intervention name: Quercetin
  description: Placebo
  arm group label: Placebo
  arm group label: Quercetin 1000 mg/day
  arm group label: Quercetin 500mg/day
  other name: Placebo
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Nathaniel Marchetti
  role: Principal Investigator
  affiliation: Temple University
  last name: Umadevi Sajjan
  phone: 2157077139
  email: uma.sajjan@temple.edu
  facility: 
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  country: United States
  url: http://clinicaltrials.gov/ct2/show/NCT01708278
  description: Phase I clinical trials to determine the safety of quercetin supplementation in COPD
  url: http://clinicaltrials.gov/ct2/show/NCT03989271
  description: Biological Effects of Quercetin in COPD
  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: Farazuddin M, Mishra R, Jing Y, Srivastava V, Comstock AT, Sajjan US. Quercetin prevents rhinovirus-induced progression of lung disease in mice with COPD phenotype. PLoS One. 2018 Jul 5;13(7):e0199612. doi: 10.1371/journal.pone.0199612. eCollection 2018.
  PMID: 29975735
  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: Han MK, Barreto TA, Martinez FJ, Comstock AT, Sajjan US. Randomised clinical trial to determine the safety of quercetin supplementation in patients with chronic obstructive pulmonary disease. BMJ Open Respir Res. 2020 Feb;7(1):e000392. doi: 10.1136/bmjresp-2018-000392.
  PMID: 32071149
  responsible party type: Principal Investigator
  investigator affiliation: Temple University
  investigator full name: Umadevi Sajjan
  investigator title: Associate Professor
  mesh term: Lung Diseases, Obstructive
  mesh term: Pulmonary Disease, Chronic Obstructive
  mesh term: Quercetin
  sharing ipd: No