<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/NCT01704859</url>
  </required_header>
  <id_info>
    <org_study_id>2010P002005</org_study_id>
    <secondary_id>1R01AR070854-01A1</secondary_id>
    <nct_id>NCT01704859</nct_id>
  </id_info>
  <brief_title>VITamin D and OmegA-3 TriaL (VITAL): Fractures, Vitamin D and Genetic Markers</brief_title>
  <official_title>VITamin D and OmegA-3 TriaL (VITAL): Fractures, Vitamin D and Genetic Markers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a randomized clinical trial in&#xD;
      25,871 U.S. men and women investigating whether taking daily dietary supplements of vitamin&#xD;
      D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing&#xD;
      cancer, heart disease, and stroke in people who do not have a prior history of these&#xD;
      illnesses. This ancillary study is being conducted among participants in VITAL and will&#xD;
      examine (1) whether vitamin D reduces incident total, non-vertebral fractures, and hip&#xD;
      fractures and (2) whether this reduction is modified by vitamin D levels&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The VITAL: Vitamin D, Fractures, and Genetic Markers is an ancillary study of the parent&#xD;
      VITAL trial (VITamin D and OmegA-3 TriaL). The study will require the adjudication of all&#xD;
      self-reported incident fracture events among 25,871 men and women. Findings from this&#xD;
      ancillary study will inform clinical practice on the role(s) of vitamin D supplements in&#xD;
      fracture prevention. This proposal will generate important positive or informative negative&#xD;
      results about effects of supplemental vitamin D3 alone on fracture risk, while also&#xD;
      elucidating the relative importance of vitamin D biomarkers and genetic variations in vitamin&#xD;
      D-related pathways on bone. Findings from the proposed ancillary study have the potential for&#xD;
      major clinical as well as public health impact for both men and women in the U.S.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 1, 2018</start_date>
  <completion_date type="Anticipated">August 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2024</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>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incident total, non-vertebral, and hip fractures</measure>
    <time_frame>5 years</time_frame>
    <description>To determine whether vitamin D supplementation will reduce incident total, non-vertebral, and hip fractures according to annual questionnaires, medical record review, and fracture adjudication.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incident total, non-vertebral, and hip fractures</measure>
    <time_frame>5 years</time_frame>
    <description>To determine whether baseline vitamin D levels and genetic variation in vitamin D-related pathways modify effects of vitamin D supplements on fractures.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">25871</enrollment>
  <condition>Fractures</condition>
  <arm_group>
    <arm_group_label>Vitamin D placebo + fish oil placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D placebo + fish oil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D + fish oil placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D + fish oil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D3 placebo</intervention_name>
    <description>Vitamin D placebo</description>
    <arm_group_label>Vitamin D placebo + fish oil</arm_group_label>
    <arm_group_label>Vitamin D placebo + fish oil placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Fish oil placebo</intervention_name>
    <description>Fish oil placebo</description>
    <arm_group_label>Vitamin D + fish oil placebo</arm_group_label>
    <arm_group_label>Vitamin D placebo + fish oil placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>omega-3 fatty acids (fish oil)</intervention_name>
    <description>Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams 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 + fish oil</arm_group_label>
    <arm_group_label>Vitamin D placebo + fish oil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D3</intervention_name>
    <description>Vitamin D3 (cholecalciferol), 2000 IU per day.</description>
    <arm_group_label>Vitamin D + fish oil</arm_group_label>
    <arm_group_label>Vitamin D + fish oil placebo</arm_group_label>
    <other_name>cholecalciferol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        All participants from the VITAL parent study (NCT01169259) were enrolled in this ancillary&#xD;
        study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Meryl S LeBoff, M.D.</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>
  <link>
    <url>http://www.vitalstudy.org/</url>
    <description>VITAL study website</description>
  </link>
  <reference>
    <citation>LeBoff MS, Yue AY, Copeland T, Cook NR, Buring JE, Manson JE. VITAL-Bone Health: rationale and design of two ancillary studies evaluating the effects of vitamin D and/or omega-3 fatty acid supplements on incident fractures and bone health outcomes in the VITamin D and OmegA-3 TriaL (VITAL). Contemp Clin Trials. 2015 Mar;41:259-68. doi: 10.1016/j.cct.2015.01.007. Epub 2015 Jan 24.</citation>
    <PMID>25623291</PMID>
  </reference>
  <reference>
    <citation>LeBoff MS, Chou SH, Murata EM, Donlon CM, Cook NR, Mora S, Lee IM, Kotler G, Bubes V, Buring JE, Manson JE. Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res. 2020 May;35(5):883-893. doi: 10.1002/jbmr.3958. Epub 2020 Jan 30.</citation>
    <PMID>31923341</PMID>
  </reference>
  <reference>
    <citation>LeBoff MS, Chou SH, Ratliff KA, Cook NR, Khurana B, Kim E, Cawthon PM, Bauer DC, Black D, Gallagher JC, Lee IM, Buring JE, Manson JE. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. N Engl J Med. 2022 Jul 28;387(4):299-309. doi: 10.1056/NEJMoa2202106.</citation>
    <PMID>35939577</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>October 9, 2012</study_first_submitted>
  <study_first_submitted_qc>October 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2023</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>Meryl LeBoff</investigator_full_name>
    <investigator_title>Director of Skeletal Health and Osteoporosis Center</investigator_title>
  </responsible_party>
  <keyword>fracture</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Bone</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/NCT01704859
org study id: 2010P002005
secondary id: 1R01AR070854-01A1
nct id: NCT01704859
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a randomized clinical trial in
      25,871 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 (1) whether vitamin D reduces incident total, non-vertebral fractures, and hip
      fractures and (2) whether this reduction is modified by vitamin D levels
The VITAL: Vitamin D, Fractures, and Genetic Markers is an ancillary study of the parent
      VITAL trial (VITamin D and OmegA-3 TriaL). The study will require the adjudication of all
      self-reported incident fracture events among 25,871 men and women. Findings from this
      ancillary study will inform clinical practice on the role(s) of vitamin D supplements in
      fracture prevention. This proposal will generate important positive or informative negative
      results about effects of supplemental vitamin D3 alone on fracture risk, while also
      elucidating the relative importance of vitamin D biomarkers and genetic variations in vitamin
      D-related pathways on bone. Findings from the proposed ancillary study have the potential for
      major clinical as well as public health impact for both men and women in the U.S.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Double Blind
measure: Incident total, non-vertebral, and hip fractures
time frame: 5 years
description: To determine whether vitamin D supplementation will reduce incident total, non-vertebral, and hip fractures according to annual questionnaires, medical record review, and fracture adjudication.
measure: Incident total, non-vertebral, and hip fractures
time frame: 5 years
description: To determine whether baseline vitamin D levels and genetic variation in vitamin D-related pathways modify effects of vitamin D supplements on fractures.
arm group label: Vitamin D placebo + fish oil placebo
arm group type: Placebo Comparator
arm group label: Vitamin D placebo + fish oil
arm group type: Active Comparator
arm group label: Vitamin D + fish oil placebo
arm group type: Active Comparator
arm group label: Vitamin D + fish oil
arm group type: Active Comparator
intervention type: Dietary Supplement
intervention name: Vitamin D3 placebo
description: Vitamin D placebo
arm group label: Vitamin D placebo + fish oil
arm group label: Vitamin D placebo + fish oil placebo
intervention type: Dietary Supplement
intervention name: Fish oil placebo
description: Fish oil placebo
arm group label: Vitamin D + fish oil placebo
arm group label: Vitamin D placebo + fish oil placebo
intervention type: Drug
intervention name: omega-3 fatty acids (fish oil)
description: Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
arm group label: Vitamin D + fish oil
arm group label: Vitamin D placebo + fish oil
intervention type: Dietary Supplement
intervention name: Vitamin D3
description: Vitamin D3 (cholecalciferol), 2000 IU per day.
arm group label: Vitamin D + fish oil
arm group label: Vitamin D + fish oil placebo
other name: cholecalciferol
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Meryl S LeBoff, M.D.
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
url: http://www.vitalstudy.org/
description: VITAL study website
citation: LeBoff MS, Yue AY, Copeland T, Cook NR, Buring JE, Manson JE. VITAL-Bone Health: rationale and design of two ancillary studies evaluating the effects of vitamin D and/or omega-3 fatty acid supplements on incident fractures and bone health outcomes in the VITamin D and OmegA-3 TriaL (VITAL). Contemp Clin Trials. 2015 Mar;41:259-68. doi: 10.1016/j.cct.2015.01.007. Epub 2015 Jan 24.
PMID: 25623291
citation: LeBoff MS, Chou SH, Murata EM, Donlon CM, Cook NR, Mora S, Lee IM, Kotler G, Bubes V, Buring JE, Manson JE. Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res. 2020 May;35(5):883-893. doi: 10.1002/jbmr.3958. Epub 2020 Jan 30.
PMID: 31923341
citation: LeBoff MS, Chou SH, Ratliff KA, Cook NR, Khurana B, Kim E, Cawthon PM, Bauer DC, Black D, Gallagher JC, Lee IM, Buring JE, Manson JE. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults. N Engl J Med. 2022 Jul 28;387(4):299-309. doi: 10.1056/NEJMoa2202106.
PMID: 35939577
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Meryl LeBoff
investigator title: Director of Skeletal Health and Osteoporosis Center
mesh term: Fractures, Bone
mesh term: Vitamin D
mesh term: Ergocalciferols
mesh term: Cholecalciferol
mesh term: Vitamins