<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/NCT02197000</url>
  </required_header>
  <id_info>
    <org_study_id>0117-14-RMC</org_study_id>
    <nct_id>NCT02197000</nct_id>
  </id_info>
  <brief_title>A Nutritional Intervention to Decrease Breast Density Among Female BRCA (BReast CAncer Susceptibility Gene) Carriers</brief_title>
  <official_title>A Nutritional Intervention to Decrease Breast Density Among Female BRCA Carriers -A Prospective Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rabin Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rabin Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether adding DIM supplement will decrease breast&#xD;
      density among female BRCA mutation carriers in two years.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Research Question: In female BRCA mutation carriers, will adding DIM (100mg*1/d, a&#xD;
      nutritional supplement), decrease breast density in two years?&#xD;
&#xD;
      Study design: A single center single arm prospective interventional study of the use of DIM&#xD;
      to decrease risk of breast cancer among female BRCA carriers.&#xD;
&#xD;
      Study population: Subjects will be female carriers of a BRCA mutation and have more than 10%&#xD;
      mammographic breast density at baseline.&#xD;
&#xD;
      Intervention: DIM supplement (100mg*1/d).&#xD;
&#xD;
      Study Time line: This will be a 2 years study. At initiation a breast mammography will be&#xD;
      performed and eligibility assessed. Follow-up visits will occur every 4 months and quality of&#xD;
      life questionnaires as well as adherence to DIM supplementation will be assessed. At the&#xD;
      initiation and every 4 months blood and urine samples will be collected for Estrogen profile.&#xD;
      At 12 and 24 months a mammography will be performed to verify changes in breast density.&#xD;
&#xD;
      Primary Endpoint: A decrease of more than 10% in breast density compared to baseline,&#xD;
      following DIM supplementation intervention among female BRCA carriers.&#xD;
&#xD;
      Study impact: Decrease in mammographic breast density was shown to be a good marker for lower&#xD;
      risk of breast cancer. This study has the potential to dramatically impact the management of&#xD;
      female BRCA carriers. If we prove that by adding a food supplement breast density is&#xD;
      decreased, we will change standard of care in these woman. In addition, the urine and blood&#xD;
      samples collected during the study will be used for future translational research on the&#xD;
      pathogenesis of breast cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 11, 2014</start_date>
  <completion_date type="Actual">October 10, 2018</completion_date>
  <primary_completion_date type="Actual">October 10, 2018</primary_completion_date>
  <phase>N/A</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>Changes in breast density compared to baseline</measure>
    <time_frame>0, 12 and 24 months following intiation</time_frame>
    <description>The amount of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) on magnetic resonance imaging (MRI)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Estrogen profile</measure>
    <time_frame>0, 4, 8, 12, 16 and 24 months following initiation</time_frame>
    <description>changes in TSH (Thyroid Stimulating Hormone), FSH (Follicle Stimulating Hormone), LH (Luteinizing Hormone), Estrogen, Prolactin, Progesterone and Testosterone compare to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Estronex Profile</measure>
    <time_frame>0, 12 and 24 months following initiation</time_frame>
    <description>changes in the 2, 4, and 16 alpha- hydroxyderivative of estrone and the 2 and 4 methoxyestrone compare to baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in Quality of life</measure>
    <time_frame>0, 4, 8, 12, 16 and 24 months following initiation</time_frame>
    <description>Quality of life will be evaluate using the Revised Illness Perception Questionnaire.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>BRCA1 Gene Mutation</condition>
  <condition>BRCA2 Gene Mutation</condition>
  <arm_group>
    <arm_group_label>DIM-Avail 100mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>women will receive DIM 100mg*1/d, a nutritional supplement for 24 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>DIM-Avail 100mg</intervention_name>
    <description>DIM 100 mg*1 daily for 2 years</description>
    <arm_group_label>DIM-Avail 100mg</arm_group_label>
    <other_name>3,3-Diindolylmethane</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women who carrier the BRCA 1\2 mutation.&#xD;
&#xD;
          -  No history of breast or ovarian malignancy.&#xD;
&#xD;
          -  i. Baseline mammographic breast density is more than 10% OR ii. Baseline breast MRI&#xD;
             with density or enhancement ≤ 2.&#xD;
&#xD;
          -  Age 18-70.&#xD;
&#xD;
          -  Absence of any psychological, familial, sociological or geographical situation&#xD;
             potentially hampering adherence to the study protocol and follow-up schedule.&#xD;
&#xD;
          -  Informed written consent must be signed according to ICH/EU GCP, before subject&#xD;
             registration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who have undergone preventive breast reduction.&#xD;
&#xD;
          -  Breast imaging demonstrating a lesion suspected to be cancerous.&#xD;
&#xD;
          -  Breast feeding or Pregnancy or planning to get pregnant.&#xD;
&#xD;
          -  Known allergy to DIM and its ingredients.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Margel, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rabin Medical Center, Beilinson campus, Petah-Tikva, Israel</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rinat Yerushalmi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rabin Medical Center, Beilinson Hospital</name>
      <address>
        <city>Petah-Tikva</city>
        <zip>49100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>July 20, 2014</study_first_submitted>
  <study_first_submitted_qc>July 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <last_update_submitted>November 9, 2020</last_update_submitted>
  <last_update_submitted_qc>November 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BRCA mutation</keyword>
  <keyword>Breast cancer</keyword>
  <keyword>Estrogen metabolism</keyword>
  <keyword>3,3-Diindolylmethane</keyword>
  <keyword>Breast density</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>3,3'-diindolylmethane</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/NCT02197000
org study id: 0117-14-RMC
nct id: NCT02197000
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine whether adding DIM supplement will decrease breast
      density among female BRCA mutation carriers in two years.
The Research Question: In female BRCA mutation carriers, will adding DIM (100mg*1/d, a
      nutritional supplement), decrease breast density in two years?

      Study design: A single center single arm prospective interventional study of the use of DIM
      to decrease risk of breast cancer among female BRCA carriers.

      Study population: Subjects will be female carriers of a BRCA mutation and have more than 10%
      mammographic breast density at baseline.

      Intervention: DIM supplement (100mg*1/d).

      Study Time line: This will be a 2 years study. At initiation a breast mammography will be
      performed and eligibility assessed. Follow-up visits will occur every 4 months and quality of
      life questionnaires as well as adherence to DIM supplementation will be assessed. At the
      initiation and every 4 months blood and urine samples will be collected for Estrogen profile.
      At 12 and 24 months a mammography will be performed to verify changes in breast density.

      Primary Endpoint: A decrease of more than 10% in breast density compared to baseline,
      following DIM supplementation intervention among female BRCA carriers.

      Study impact: Decrease in mammographic breast density was shown to be a good marker for lower
      risk of breast cancer. This study has the potential to dramatically impact the management of
      female BRCA carriers. If we prove that by adding a food supplement breast density is
      decreased, we will change standard of care in these woman. In addition, the urine and blood
      samples collected during the study will be used for future translational research on the
      pathogenesis of breast cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Changes in breast density compared to baseline
time frame: 0, 12 and 24 months following intiation
description: The amount of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) on magnetic resonance imaging (MRI)
measure: Estrogen profile
time frame: 0, 4, 8, 12, 16 and 24 months following initiation
description: changes in TSH (Thyroid Stimulating Hormone), FSH (Follicle Stimulating Hormone), LH (Luteinizing Hormone), Estrogen, Prolactin, Progesterone and Testosterone compare to baseline
measure: The Estronex Profile
time frame: 0, 12 and 24 months following initiation
description: changes in the 2, 4, and 16 alpha- hydroxyderivative of estrone and the 2 and 4 methoxyestrone compare to baseline
measure: change in Quality of life
time frame: 0, 4, 8, 12, 16 and 24 months following initiation
description: Quality of life will be evaluate using the Revised Illness Perception Questionnaire.
arm group label: DIM-Avail 100mg
arm group type: Experimental
description: women will receive DIM 100mg*1/d, a nutritional supplement for 24 months.
intervention type: Dietary Supplement
intervention name: DIM-Avail 100mg
description: DIM 100 mg*1 daily for 2 years
arm group label: DIM-Avail 100mg
other name: 3,3-Diindolylmethane
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: David Margel, MD, PhD
role: Principal Investigator
affiliation: Rabin Medical Center, Beilinson campus, Petah-Tikva, Israel
last name: Rinat Yerushalmi, MD
role: Principal Investigator
affiliation: Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel
facility: 
country: Israel
responsible party type: Sponsor
mesh term: 3,3'-diindolylmethane
sharing ipd: No