<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/NCT02239874</url>
  </required_header>
  <id_info>
    <org_study_id>2014P000895</org_study_id>
    <secondary_id>R01CA178263</secondary_id>
    <nct_id>NCT02239874</nct_id>
  </id_info>
  <brief_title>VITamin D and OmegA-3 TriaL: Effects on Mammographic Density and Breast Tissue</brief_title>
  <acronym>VITAL</acronym>
  <official_title>THE EFFECTS OF VITAMIN D ON MAMMOGRAPHIC DENSITY AND BREAST TISSUE</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is an ongoing randomized clinical trial&#xD;
      in 25,875 U.S. men and women investigating whether taking daily dietary supplements of&#xD;
      vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of&#xD;
      developing cancer, heart disease, and stroke in people who do not have a prior history of&#xD;
      these illnesses. This ancillary study is being conducted among participants in VITAL and will&#xD;
      examine whether vitamin D effects mammographic breast density, mammographic texture features,&#xD;
      and gene expression profiles in breast biopsy tissue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Mammographic density is one of the strongest risk factors for breast cancer. It is predictive&#xD;
      of breast cancer risk for at least 10 years in the futue and has been suggested as a&#xD;
      surrogate marker of breast cancer risk. Several states now mandate release of mammographic&#xD;
      density data to women. However, except for anti-hormonal therapies (e.g., tamoxifen), no&#xD;
      interventions have been proven to reduce breast density. Thus, testing promising,&#xD;
      well-tolerated interventions that might affect mammographic density is of substantial&#xD;
      interest. Several lines of evidence suggest that vitamin D may play a role in breast density&#xD;
      and breast carcinogenesis. Vitamin D reduces proliferation and promotes differentiation and&#xD;
      apoptosis in breast cells in culture. However, no large-scale randomized studies have&#xD;
      examined the impact of vitamin D on mammographic density. We propose to examine the&#xD;
      randomized effects vitamin D3 on mammographic breast density in the NIH sponsored VITamin D&#xD;
      and OmegA-3 TriaL (VITAL), an ongoing randomized, double blind, trial testing vitamin D3&#xD;
      (2,000 IU/day cholecalciferol) and omega-3 fatty acids (840 mg eicosapentaenoic acid [EPA]+&#xD;
      docosahexaenoic acid [DHA]) in the primary prevention of cancer and cardiovascular disease in&#xD;
      a multi-ethnic population of over 24,000 men and women. In this ancillary sub study,&#xD;
      mammograms will be obtained on 4000 women age 55-67 years (25% African-American), from&#xD;
      baseline (pre-randomization) and after 1 and 4 years of randomized therapy. Centrally&#xD;
      processed quantitative mammographic density and texture variation will be measured. We will&#xD;
      determine if randomized vitamin D treatment is associated with change in mammographic&#xD;
      features, and whether effects are modified by baseline mammographic density, and baseline&#xD;
      25(OH) vitamin D levels. In addition, tissue samples from women in VITAL undergoing breast&#xD;
      biopsy/surgery, for both nonmalignant and malignant conditions, will be collected.&#xD;
      Quantitative morphological measures, as well as gene expression assays targeting vitamin D&#xD;
      activation and breast carcinogenesis pathways, will be performed on collected tissues among&#xD;
      women on randomized vitamin D3 compared with placebo. This ancillary study provides a timely&#xD;
      opportunity to test comprehensively the effects of vitamin D3 on mammographic features and&#xD;
      breast tissue biology in a randomized setting at minimal additional cost.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Actual">March 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mammographic breast density</measure>
    <time_frame>change baseline to 4 years</time_frame>
    <description>We will collect baseline (pre-randomization), 1-year and 4-year follow-up mammograms, as well as tissue specimens from women undergoing breast biopsy/surgery for malignant and nonmalignant disease, to further elucidate the role of vitamin D on mammographic features and breast tissue biology</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Breast tissue</measure>
    <time_frame>4 years</time_frame>
    <description>Quantitative morphological measures, as well as gene expression assays targeting vitamin D activation and breast carcinogenesis pathways, will be performed on collected tissues among women on randomized vitamin D3 compared with placebo</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">3894</enrollment>
  <condition>Benign Breast Disease</condition>
  <arm_group>
    <arm_group_label>Vitamin D placebo and fish oil placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>vitamin D placebo + fish oil placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fish oil and vitamin D placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D placebo and 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D and fish oil placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D3 (cholecalciferol), 2000 IU per day and fish oil placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D and fish oil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D3 (cholecalciferol), 2000 IU per day and 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D and fish oil placebo</intervention_name>
    <description>Vitamin D3 (cholecalciferol), 2000 IU per day and fish oil placebo</description>
    <arm_group_label>Vitamin D and fish oil placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Fish oil and vitamin D placebo</intervention_name>
    <description>840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])</description>
    <arm_group_label>Fish oil and vitamin D placebo</arm_group_label>
    <other_name>840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D placebo and fish oil placebo</intervention_name>
    <description>placebo</description>
    <arm_group_label>Vitamin D placebo and fish oil placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D and fish oil</intervention_name>
    <description>Vitamin D3 (cholecalciferol), 2000 IU per day and 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])</description>
    <arm_group_label>Vitamin D and fish oil</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  part of parent VITAL trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Men,&#xD;
&#xD;
          -  women with breast cancer&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>67 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rulla M Tamimi, ScD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kathy Rexrode, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>September 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>April 6, 2022</last_update_submitted>
  <last_update_submitted_qc>April 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Rulla Tamimi</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>mammographic breast density, breast disease, breast tissue</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Diseases</mesh_term>
    <mesh_term>Fibrocystic Breast Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Ergocalciferols</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
    <mesh_term>Vitamins</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02239874
org study id: 2014P000895
secondary id: R01CA178263
nct id: NCT02239874
lead sponsor: 
collaborator: 
has dmc: No
The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is an ongoing randomized clinical trial
      in 25,875 U.S. men and women investigating whether taking daily dietary supplements of
      vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of
      developing cancer, heart disease, and stroke in people who do not have a prior history of
      these illnesses. This ancillary study is being conducted among participants in VITAL and will
      examine whether vitamin D effects mammographic breast density, mammographic texture features,
      and gene expression profiles in breast biopsy tissue.
Mammographic density is one of the strongest risk factors for breast cancer. It is predictive
      of breast cancer risk for at least 10 years in the futue and has been suggested as a
      surrogate marker of breast cancer risk. Several states now mandate release of mammographic
      density data to women. However, except for anti-hormonal therapies (e.g., tamoxifen), no
      interventions have been proven to reduce breast density. Thus, testing promising,
      well-tolerated interventions that might affect mammographic density is of substantial
      interest. Several lines of evidence suggest that vitamin D may play a role in breast density
      and breast carcinogenesis. Vitamin D reduces proliferation and promotes differentiation and
      apoptosis in breast cells in culture. However, no large-scale randomized studies have
      examined the impact of vitamin D on mammographic density. We propose to examine the
      randomized effects vitamin D3 on mammographic breast density in the NIH sponsored VITamin D
      and OmegA-3 TriaL (VITAL), an ongoing randomized, double blind, trial testing vitamin D3
      (2,000 IU/day cholecalciferol) and omega-3 fatty acids (840 mg eicosapentaenoic acid [EPA]+
      docosahexaenoic acid [DHA]) in the primary prevention of cancer and cardiovascular disease in
      a multi-ethnic population of over 24,000 men and women. In this ancillary sub study,
      mammograms will be obtained on 4000 women age 55-67 years (25% African-American), from
      baseline (pre-randomization) and after 1 and 4 years of randomized therapy. Centrally
      processed quantitative mammographic density and texture variation will be measured. We will
      determine if randomized vitamin D treatment is associated with change in mammographic
      features, and whether effects are modified by baseline mammographic density, and baseline
      25(OH) vitamin D levels. In addition, tissue samples from women in VITAL undergoing breast
      biopsy/surgery, for both nonmalignant and malignant conditions, will be collected.
      Quantitative morphological measures, as well as gene expression assays targeting vitamin D
      activation and breast carcinogenesis pathways, will be performed on collected tissues among
      women on randomized vitamin D3 compared with placebo. This ancillary study provides a timely
      opportunity to test comprehensively the effects of vitamin D3 on mammographic features and
      breast tissue biology in a randomized setting at minimal additional cost.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Other
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Mammographic breast density
time frame: change baseline to 4 years
description: We will collect baseline (pre-randomization), 1-year and 4-year follow-up mammograms, as well as tissue specimens from women undergoing breast biopsy/surgery for malignant and nonmalignant disease, to further elucidate the role of vitamin D on mammographic features and breast tissue biology
measure: Breast tissue
time frame: 4 years
description: Quantitative morphological measures, as well as gene expression assays targeting vitamin D activation and breast carcinogenesis pathways, will be performed on collected tissues among women on randomized vitamin D3 compared with placebo
arm group label: Vitamin D placebo and fish oil placebo
arm group type: Placebo Comparator
description: vitamin D placebo + fish oil placebo
arm group label: Fish oil and vitamin D placebo
arm group type: Active Comparator
description: Vitamin D placebo and 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])
arm group label: Vitamin D and fish oil placebo
arm group type: Active Comparator
description: Vitamin D3 (cholecalciferol), 2000 IU per day and fish oil placebo
arm group label: Vitamin D and fish oil
arm group type: Active Comparator
description: Vitamin D3 (cholecalciferol), 2000 IU per day and 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])
intervention type: Dietary Supplement
intervention name: Vitamin D and fish oil placebo
description: Vitamin D3 (cholecalciferol), 2000 IU per day and fish oil placebo
arm group label: Vitamin D and fish oil placebo
intervention type: Dietary Supplement
intervention name: Fish oil and vitamin D placebo
description: 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])
arm group label: Fish oil and vitamin D placebo
other name: 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])
intervention type: Dietary Supplement
intervention name: Vitamin D placebo and fish oil placebo
description: placebo
arm group label: Vitamin D placebo and fish oil placebo
intervention type: Dietary Supplement
intervention name: Vitamin D and fish oil
description: Vitamin D3 (cholecalciferol), 2000 IU per day and 840 mg of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA])
arm group label: Vitamin D and fish oil
criteria: 
gender: Female
minimum age: 55 Years
maximum age: 67 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Rulla M Tamimi, ScD
role: Principal Investigator
affiliation: Brigham and Women's Hospital
last name: Kathy Rexrode, MD
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Rulla Tamimi
investigator title: Associate Professor of Medicine
mesh term: Breast Diseases
mesh term: Fibrocystic Breast Disease
mesh term: Vitamin D
mesh term: Ergocalciferols
mesh term: Cholecalciferol
mesh term: Vitamins