<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/NCT01720147</url>
  </required_header>
  <id_info>
    <org_study_id>2011-2049</org_study_id>
    <secondary_id>1R01FD004383-01A1</secondary_id>
    <nct_id>NCT01720147</nct_id>
  </id_info>
  <brief_title>Quercetin in Children With Fanconi Anemia; a Pilot Study</brief_title>
  <official_title>Quercetin in Children With Fanconi Anemia; a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Food and Drug Administration (FDA)</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone&#xD;
      marrow failure (BMF), congenital abnormalities and a predisposition to malignancy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Current therapies for children with Fanconi anemia (FA) and bone marrow failure, i.e.&#xD;
      androgens or bone marrow transplantation, are associated with significant morbidity and&#xD;
      mortality.&#xD;
&#xD;
      This is a pilot study aiming to assess feasibility, toxicity and pharmacokinetics of oral&#xD;
      Quercetin therapy in patients with FA. This is a first step towards a clinical study of the&#xD;
      efficacy of Quercetin therapy in delaying progression of BMF in FA.&#xD;
&#xD;
      Additional correlative studies will include assessment of impact of Quercetin on reduction of&#xD;
      Reactive Oxygen Species (ROS), maintenance or improvement of hematopoietic stem cell (HSC)&#xD;
      reserve, improvement of hematopoiesis (i.e. peripheral counts) and insulin&#xD;
      sensitivity/glucose tolerance.&#xD;
&#xD;
      This study is an open-label single arm study.&#xD;
&#xD;
      Funding Source - FDA OOPD&#xD;
&#xD;
      Accrual closed for the main study. Expansion cohort added to observe additional patients at&#xD;
      the desired dose.&#xD;
&#xD;
      Expansion Cohort:&#xD;
&#xD;
      The second and third cohort of participants completed the study treatment as expected,&#xD;
      tolerating Quercetin well without any DLT. Based on the PK and ROS analyses, the dose was&#xD;
      increased for the fourth cohort (subjects #10-12). To observe additional patients at the&#xD;
      desired dose, an expansion cohort is being added. Up to 20 patients will be enrolled in the&#xD;
      expansion cohort. The purpose of the expansion cohort is to assess the effects of quercetin&#xD;
      supplement at the desired dose on clinical and biological endpoints.&#xD;
&#xD;
      Patients in the expansion cohort will receive quercetin treatment for the first 26 weeks.&#xD;
      Patients will be able to continue quercetin supplement after the completion of the study&#xD;
      period of 26 weeks if they wish. If patients decide to continue quercetin after the first 26&#xD;
      weeks, quercetin will be provided by the investigational pharmacy for up to 1 year. Patients&#xD;
      who continue quercetin supplement after 26 weeks, but discontinue quercetin before 1 year&#xD;
      will be followed through the 1 year visit. Patients who discontinue quercetin supplement any&#xD;
      time after the 1 year visit will be followed through the 2 year visit.&#xD;
&#xD;
      Patients previously enrolled in the initial phase of the study (cohorts 1-4) may be&#xD;
      considered for enrollment on the expansion cohort of the study provided they meet all&#xD;
      inclusion and exclusion criteria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">October 26, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measure the ability to administer twice daily oral quercetin therapy in patients with Fanconi Anemia (FA).</measure>
    <time_frame>4 months (16 weeks)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Measure safety of oral quercetin therapy in patients with FA</measure>
    <time_frame>4 months (16 weeks)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To measure pharmacokinetics (PK) of oral quercetin therapy in patients with FA</measure>
    <time_frame>4 months (16 weeks)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To measure the impact of quercetin therapy on reduction of Reactive Oxygen Species (ROS).</measure>
    <time_frame>4 months (16 weeks) and 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with improved hematopoiesis.</measure>
    <time_frame>4 months (16 weeks) and 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure the preservation of hematopoietic stem cell reserve in patients with FA</measure>
    <time_frame>4 months (16 weeks) and 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure the impact of quercetin therapy on changes in insulin sensitivity/glucose tolerance.</measure>
    <time_frame>4 month (16 weeks) and 1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Fanconi Anemia</condition>
  <arm_group>
    <arm_group_label>Quercetin - Dietary Supplement</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Quercetin will be given orally on a twice a day schedule starting with weight adjusted dose for a maximum total daily dose of 1500 mg/day, for 4 months (16 weeks). Pharmacokinetics (PK) data will be analyzed after each cohort of 3 patients and will be used to optimize the dosing schedule (if required) for subsequent patients.&#xD;
An expansion cohort has been added to the study protocol. Up to 20 patients may be enrolled. The dose utilized will be the same as the max weight adjusted dose that showed biological activity in our last cohort of patients (subjects #10-12 from above).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Quercetin (dietary supplement)</intervention_name>
    <description>Quercetin will be given orally on a twice a day schedule starting with weight adjusted dose for a maximum total daily dose of 1500 mg/day, for 4 months (16 weeks). Pharmacokinetics (PK) data will be analyzed after each cohort of 3 patients and will be used to optimize the dosing schedule (if required)for subsequent patients.&#xD;
An expansion cohort has been added to the study protocol. Up to 20 patients may be enrolled. The dose utilized will be the same as the max weight adjusted dose that showed biological activity in our last cohort of patients (subjects #10-12 from above).</description>
    <arm_group_label>Quercetin - Dietary Supplement</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of FA proven by DEB test or molecular testing&#xD;
&#xD;
          -  Able to take enteral medication&#xD;
&#xD;
          -  All age groups, including adults&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with morphological evidence of myelodysplasia or leukemia&#xD;
&#xD;
          -  Renal failure requiring dialysis&#xD;
&#xD;
          -  Total bilirubin &gt; 3 mg/dl and/or SGPT &gt;200 at time of enrollment&#xD;
&#xD;
          -  Patients who are pregnant or breastfeeding or are at risk of pregnancy and are unable&#xD;
             to use acceptable methods of birth control during the length of the study&#xD;
&#xD;
          -  Patients receiving cyclosporine or digoxin therapy or are unable to discontinue either&#xD;
             treatment due to medical reasons&#xD;
&#xD;
          -  Patients who have received quercetin supplementation or other antioxidants within the&#xD;
             last 30 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Parinda Mehta, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <last_update_submitted>February 3, 2023</last_update_submitted>
  <last_update_submitted_qc>February 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fanconi Anemia</keyword>
  <keyword>FA</keyword>
  <keyword>Quercetin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fanconi Syndrome</mesh_term>
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Fanconi Anemia</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>


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/NCT01720147
org study id: 2011-2049
secondary id: 1R01FD004383-01A1
nct id: NCT01720147
lead sponsor: 
collaborator: 
has dmc: Yes
Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone
      marrow failure (BMF), congenital abnormalities and a predisposition to malignancy.
Current therapies for children with Fanconi anemia (FA) and bone marrow failure, i.e.
      androgens or bone marrow transplantation, are associated with significant morbidity and
      mortality.

      This is a pilot study aiming to assess feasibility, toxicity and pharmacokinetics of oral
      Quercetin therapy in patients with FA. This is a first step towards a clinical study of the
      efficacy of Quercetin therapy in delaying progression of BMF in FA.

      Additional correlative studies will include assessment of impact of Quercetin on reduction of
      Reactive Oxygen Species (ROS), maintenance or improvement of hematopoietic stem cell (HSC)
      reserve, improvement of hematopoiesis (i.e. peripheral counts) and insulin
      sensitivity/glucose tolerance.

      This study is an open-label single arm study.

      Funding Source - FDA OOPD

      Accrual closed for the main study. Expansion cohort added to observe additional patients at
      the desired dose.

      Expansion Cohort:

      The second and third cohort of participants completed the study treatment as expected,
      tolerating Quercetin well without any DLT. Based on the PK and ROS analyses, the dose was
      increased for the fourth cohort (subjects #10-12). To observe additional patients at the
      desired dose, an expansion cohort is being added. Up to 20 patients will be enrolled in the
      expansion cohort. The purpose of the expansion cohort is to assess the effects of quercetin
      supplement at the desired dose on clinical and biological endpoints.

      Patients in the expansion cohort will receive quercetin treatment for the first 26 weeks.
      Patients will be able to continue quercetin supplement after the completion of the study
      period of 26 weeks if they wish. If patients decide to continue quercetin after the first 26
      weeks, quercetin will be provided by the investigational pharmacy for up to 1 year. Patients
      who continue quercetin supplement after 26 weeks, but discontinue quercetin before 1 year
      will be followed through the 1 year visit. Patients who discontinue quercetin supplement any
      time after the 1 year visit will be followed through the 2 year visit.

      Patients previously enrolled in the initial phase of the study (cohorts 1-4) may be
      considered for enrollment on the expansion cohort of the study provided they meet all
      inclusion and exclusion criteria.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Measure the ability to administer twice daily oral quercetin therapy in patients with Fanconi Anemia (FA).
time frame: 4 months (16 weeks)
measure: Measure safety of oral quercetin therapy in patients with FA
time frame: 4 months (16 weeks)
measure: To measure pharmacokinetics (PK) of oral quercetin therapy in patients with FA
time frame: 4 months (16 weeks)
measure: To measure the impact of quercetin therapy on reduction of Reactive Oxygen Species (ROS).
time frame: 4 months (16 weeks) and 1 year
measure: Number of participants with improved hematopoiesis.
time frame: 4 months (16 weeks) and 1 year
measure: Measure the preservation of hematopoietic stem cell reserve in patients with FA
time frame: 4 months (16 weeks) and 1 year
measure: To measure the impact of quercetin therapy on changes in insulin sensitivity/glucose tolerance.
time frame: 4 month (16 weeks) and 1 year
arm group label: Quercetin - Dietary Supplement
arm group type: Experimental
description: Quercetin will be given orally on a twice a day schedule starting with weight adjusted dose for a maximum total daily dose of 1500 mg/day, for 4 months (16 weeks). Pharmacokinetics (PK) data will be analyzed after each cohort of 3 patients and will be used to optimize the dosing schedule (if required) for subsequent patients.
An expansion cohort has been added to the study protocol. Up to 20 patients may be enrolled. The dose utilized will be the same as the max weight adjusted dose that showed biological activity in our last cohort of patients (subjects #10-12 from above).
intervention type: Drug
intervention name: Quercetin (dietary supplement)
description: Quercetin will be given orally on a twice a day schedule starting with weight adjusted dose for a maximum total daily dose of 1500 mg/day, for 4 months (16 weeks). Pharmacokinetics (PK) data will be analyzed after each cohort of 3 patients and will be used to optimize the dosing schedule (if required)for subsequent patients.
An expansion cohort has been added to the study protocol. Up to 20 patients may be enrolled. The dose utilized will be the same as the max weight adjusted dose that showed biological activity in our last cohort of patients (subjects #10-12 from above).
arm group label: Quercetin - Dietary Supplement
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Parinda Mehta, MD
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fanconi Syndrome
mesh term: Anemia
mesh term: Fanconi Anemia
mesh term: Quercetin
sharing ipd: No