<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/NCT03004508</url>
  </required_header>
  <id_info>
    <org_study_id>IDN5933</org_study_id>
    <nct_id>NCT03004508</nct_id>
  </id_info>
  <brief_title>Safety of Ginkgo Biloba Leaf Extract</brief_title>
  <acronym>GiBiEx</acronym>
  <official_title>Antioxidant Effect of Treatment With Ginkgo Biloba L. Leaf Extract (IDN 5933) on DNA Cell Maintenance and Genomic Stability: A Randomised Study Versus Placebo</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS San Raffaele</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Indena S.p.A</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>IRCCS San Raffaele</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary objective: The primary objective of this study is to assess the effect of Ginkgo&#xD;
      biloba L. leaf extract (IDN 5933) in comparison to placebo in human subjects treated at&#xD;
      therapeutic doses for 6 months on the level of DNA damage and genomic instability, measured&#xD;
      with the Comet Assay and the Micronucleus assay, respectively .&#xD;
&#xD;
      Secondary objective:&#xD;
&#xD;
      The secondary objective of this study is to provide a preliminary assessment of the safety of&#xD;
      Ginkgo biloba L. leaf extract (IDN 5933) in human subjects treated at therapeutic doses in&#xD;
      term of adverse drug reaction, hepatotoxicity, genotoxicity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be a randomised clinical trial comparing subjects receiving twice-daily doses&#xD;
      of either 120-mg of Ginkgo biloba L. leaf extract (IDN 5933) or placebo for a 6 months&#xD;
      period.&#xD;
&#xD;
      Primary Endpoints:&#xD;
&#xD;
        -  DNA Damage assessed with the Comet assay as proportion of DNA in the tail.&#xD;
&#xD;
        -  Micronucleus frequency (MN) in peripheral blood lymphocytes (Frequency per 1000&#xD;
           binucleated cells).&#xD;
&#xD;
      Secondary Endpoints:&#xD;
&#xD;
        -  Complete clinical assessment at the beginning and at the end of the study.&#xD;
&#xD;
        -  Occurrence of Adverse drug reactions in individuals treated with GBE or placebo.&#xD;
&#xD;
        -  Liver functions will be monitored according to biological laboratory examinations and&#xD;
           clinical symptoms. A subgroup of individuals will be monitored also for genetic&#xD;
           parameters concerning expression patterns of genes putatively associated to early events&#xD;
           of HCC carcinogenesis Clinical and biological parameters will be measured in the study&#xD;
           groups at the beginning (T0) and at the end of the study (T2).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>July 2015</start_date>
  <completion_date type="Anticipated">January 2017</completion_date>
  <primary_completion_date type="Anticipated">December 2016</primary_completion_date>
  <phase>Phase 2</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>DNA Damage</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>DNA Damage assessed with the Comet assay as proportion of DNA in the tail</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Micronucleus frequency</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Micronucleus frequency (MN) in peripheral blood lymphocytes (Frequency per 1000 binucleated cells)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical assessment</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Complete clinical assessment at the beginning and at the end of the study by physiological parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver functions</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Liver functions will be monitored according to biological laboratory examinations and clinical symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene Expression</measure>
    <time_frame>A subgroup of individuals will be monitored also through study completion, an average of 1 year</time_frame>
    <description>Expression patterns of genes putatively associated to early events of HCC carcinogenesis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse drug reactions</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Occurrence of Adverse drug reactions in individuals treated with GBE or placebo</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Gingko biloba Extract</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Gingko Biloba Extract</intervention_name>
    <description>120mg/day, twice a day, 6 month</description>
    <arm_group_label>Gingko biloba Extract</arm_group_label>
    <other_name>IDN 5933</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>120mg/day, twice a day, 6 month</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female senior, residents of nursing homes, with no known clinically&#xD;
             significant pathology as assessed by the investigator&#xD;
&#xD;
          -  Life expectancy of greater than 1 year&#xD;
&#xD;
          -  Subjects must have given written informed consent in accordance with ICH-GCP&#xD;
             (International Conference on Harmonization - Good Clinical Practice) and local laws&#xD;
             and regulations&#xD;
&#xD;
        To perform the experiment in a typical population treated with Ginkgo biloba L. leaf&#xD;
        extract ( IDN 5933) the study will be performed among the residents of nursing homes among&#xD;
        the structures of the San Raffaele network, i.e., The San Raffaele Montecompatri, the San&#xD;
        Raffaele Rocca di Papa and the San Raffaele Sabaudia . The use of institutionalised&#xD;
        subjects will allow a good compliance to the treatment, which will be administered by the&#xD;
        nursing homes nurses.&#xD;
&#xD;
        Subjects meeting inclusion criteria and signing the informed consent will be randomised to&#xD;
        receive 120-mg/twice per day of Ginkgo biloba L. leaf extract ( IDN 5933) or placebo.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Life expectancy of less than 1 year&#xD;
&#xD;
          -  Treatment with anticoagulant and antiplatelet drugs in subjects with previous report&#xD;
             of increased bleeding tendency&#xD;
&#xD;
          -  Cognitive impairment&#xD;
&#xD;
          -  Refuse to sign the informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stefano Bonassi, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS San Raffaele</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IRCCS San Raffaele Pisana</name>
      <address>
        <city>Rome</city>
        <zip>00166</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>National Toxicology Program. Toxicology and carcinogenesis studies of Ginkgo biloba extract (CAS No. 90045-36-6) in F344/N rats and B6C3F1/N mice (Gavage studies). Natl Toxicol Program Tech Rep Ser. 2013 Mar;(578):1-183.</citation>
    <PMID>23652021</PMID>
  </results_reference>
  <results_reference>
    <citation>Russo P, Frustaci A, Del Bufalo A, Fini M, Cesario A. Multitarget drugs of plants origin acting on Alzheimer's disease. Curr Med Chem. 2013;20(13):1686-93. doi: 10.2174/0929867311320130008.</citation>
    <PMID>23410167</PMID>
  </results_reference>
  <results_reference>
    <citation>Heinonen T, Gaus W. Cross matching observations on toxicological and clinical data for the assessment of tolerability and safety of Ginkgo biloba leaf extract. Toxicology. 2015 Jan 2;327:95-115. doi: 10.1016/j.tox.2014.10.013. Epub 2014 Nov 11.</citation>
    <PMID>25446328</PMID>
  </results_reference>
  <results_reference>
    <citation>Luo Y, Smith JV, Paramasivam V, Burdick A, Curry KJ, Buford JP, Khan I, Netzer WJ, Xu H, Butko P. Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12197-202. doi: 10.1073/pnas.182425199. Epub 2002 Sep 4.</citation>
    <PMID>12213959</PMID>
  </results_reference>
  <results_reference>
    <citation>Bonassi S, Znaor A, Ceppi M, Lando C, Chang WP, Holland N, Kirsch-Volders M, Zeiger E, Ban S, Barale R, Bigatti MP, Bolognesi C, Cebulska-Wasilewska A, Fabianova E, Fucic A, Hagmar L, Joksic G, Martelli A, Migliore L, Mirkova E, Scarfi MR, Zijno A, Norppa H, Fenech M. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis. 2007 Mar;28(3):625-31. doi: 10.1093/carcin/bgl177. Epub 2006 Sep 14.</citation>
    <PMID>16973674</PMID>
  </results_reference>
  <results_reference>
    <citation>Collins A, Koppen G, Valdiglesias V, Dusinska M, Kruszewski M, Moller P, Rojas E, Dhawan A, Benzie I, Coskun E, Moretti M, Speit G, Bonassi S; ComNet project. The comet assay as a tool for human biomonitoring studies: the ComNet project. Mutat Res Rev Mutat Res. 2014 Jan-Mar;759:27-39. doi: 10.1016/j.mrrev.2013.10.001. Epub 2013 Oct 31.</citation>
    <PMID>24184488</PMID>
  </results_reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>December 29, 2016</last_update_submitted>
  <last_update_submitted_qc>December 29, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 30, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS San Raffaele</investigator_affiliation>
    <investigator_full_name>Stefano Bonassi</investigator_full_name>
    <investigator_title>Head, Clinical and Molecular Epidemiology</investigator_title>
  </responsible_party>
  <keyword>Ginkgo Biloba Extract</keyword>
  <keyword>Safety</keyword>
  <keyword>Genomic Stability</keyword>
  <keyword>DNA cell maintenance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Genomic Instability</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>March 1, 2017</submitted>
    <returned>April 12, 2017</returned>
    <submitted>April 26, 2017</submitted>
    <returned>August 8, 2017</returned>
  </pending_results>
  <!-- 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/NCT03004508
org study id: IDN5933
nct id: NCT03004508
lead sponsor: 
collaborator: 
has dmc: No
Primary objective: The primary objective of this study is to assess the effect of Ginkgo
      biloba L. leaf extract (IDN 5933) in comparison to placebo in human subjects treated at
      therapeutic doses for 6 months on the level of DNA damage and genomic instability, measured
      with the Comet Assay and the Micronucleus assay, respectively .

      Secondary objective:

      The secondary objective of this study is to provide a preliminary assessment of the safety of
      Ginkgo biloba L. leaf extract (IDN 5933) in human subjects treated at therapeutic doses in
      term of adverse drug reaction, hepatotoxicity, genotoxicity.
The study will be a randomised clinical trial comparing subjects receiving twice-daily doses
      of either 120-mg of Ginkgo biloba L. leaf extract (IDN 5933) or placebo for a 6 months
      period.

      Primary Endpoints:

        -  DNA Damage assessed with the Comet assay as proportion of DNA in the tail.

        -  Micronucleus frequency (MN) in peripheral blood lymphocytes (Frequency per 1000
           binucleated cells).

      Secondary Endpoints:

        -  Complete clinical assessment at the beginning and at the end of the study.

        -  Occurrence of Adverse drug reactions in individuals treated with GBE or placebo.

        -  Liver functions will be monitored according to biological laboratory examinations and
           clinical symptoms. A subgroup of individuals will be monitored also for genetic
           parameters concerning expression patterns of genes putatively associated to early events
           of HCC carcinogenesis Clinical and biological parameters will be measured in the study
           groups at the beginning (T0) and at the end of the study (T2).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: DNA Damage
time frame: through study completion, an average of 1 year
description: DNA Damage assessed with the Comet assay as proportion of DNA in the tail
measure: Micronucleus frequency
time frame: through study completion, an average of 1 year
description: Micronucleus frequency (MN) in peripheral blood lymphocytes (Frequency per 1000 binucleated cells)
measure: Clinical assessment
time frame: through study completion, an average of 1 year
description: Complete clinical assessment at the beginning and at the end of the study by physiological parameters
measure: Liver functions
time frame: through study completion, an average of 1 year
description: Liver functions will be monitored according to biological laboratory examinations and clinical symptoms
measure: Gene Expression
time frame: A subgroup of individuals will be monitored also through study completion, an average of 1 year
description: Expression patterns of genes putatively associated to early events of HCC carcinogenesis
measure: Adverse drug reactions
time frame: through study completion, an average of 1 year
description: Occurrence of Adverse drug reactions in individuals treated with GBE or placebo
arm group label: Gingko biloba Extract
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Dietary Supplement
intervention name: Gingko Biloba Extract
description: 120mg/day, twice a day, 6 month
arm group label: Gingko biloba Extract
other name: IDN 5933
intervention type: Dietary Supplement
intervention name: Placebo
description: 120mg/day, twice a day, 6 month
arm group label: Placebo
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Stefano Bonassi, PhD
role: Principal Investigator
affiliation: IRCCS San Raffaele
facility: 
country: Italy
citation: National Toxicology Program. Toxicology and carcinogenesis studies of Ginkgo biloba extract (CAS No. 90045-36-6) in F344/N rats and B6C3F1/N mice (Gavage studies). Natl Toxicol Program Tech Rep Ser. 2013 Mar;(578):1-183.
PMID: 23652021
citation: Russo P, Frustaci A, Del Bufalo A, Fini M, Cesario A. Multitarget drugs of plants origin acting on Alzheimer's disease. Curr Med Chem. 2013;20(13):1686-93. doi: 10.2174/0929867311320130008.
PMID: 23410167
citation: Heinonen T, Gaus W. Cross matching observations on toxicological and clinical data for the assessment of tolerability and safety of Ginkgo biloba leaf extract. Toxicology. 2015 Jan 2;327:95-115. doi: 10.1016/j.tox.2014.10.013. Epub 2014 Nov 11.
PMID: 25446328
citation: Luo Y, Smith JV, Paramasivam V, Burdick A, Curry KJ, Buford JP, Khan I, Netzer WJ, Xu H, Butko P. Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12197-202. doi: 10.1073/pnas.182425199. Epub 2002 Sep 4.
PMID: 12213959
citation: Bonassi S, Znaor A, Ceppi M, Lando C, Chang WP, Holland N, Kirsch-Volders M, Zeiger E, Ban S, Barale R, Bigatti MP, Bolognesi C, Cebulska-Wasilewska A, Fabianova E, Fucic A, Hagmar L, Joksic G, Martelli A, Migliore L, Mirkova E, Scarfi MR, Zijno A, Norppa H, Fenech M. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis. 2007 Mar;28(3):625-31. doi: 10.1093/carcin/bgl177. Epub 2006 Sep 14.
PMID: 16973674
citation: Collins A, Koppen G, Valdiglesias V, Dusinska M, Kruszewski M, Moller P, Rojas E, Dhawan A, Benzie I, Coskun E, Moretti M, Speit G, Bonassi S; ComNet project. The comet assay as a tool for human biomonitoring studies: the ComNet project. Mutat Res Rev Mutat Res. 2014 Jan-Mar;759:27-39. doi: 10.1016/j.mrrev.2013.10.001. Epub 2013 Oct 31.
PMID: 24184488
responsible party type: Principal Investigator
investigator affiliation: IRCCS San Raffaele
investigator full name: Stefano Bonassi
investigator title: Head, Clinical and Molecular Epidemiology
mesh term: Genomic Instability
sharing ipd: Undecided
submitted: March 1, 2017
returned: April 12, 2017
submitted: April 26, 2017
returned: August 8, 2017