<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/NCT01696435</url>
  </required_header>
  <id_info>
    <org_study_id>2010-P-001881</org_study_id>
    <secondary_id>R01MH091448</secondary_id>
    <nct_id>NCT01696435</nct_id>
  </id_info>
  <brief_title>VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL</brief_title>
  <acronym>VITAL-DEP</acronym>
  <official_title>VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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 25,871 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 or fish oil: 1) reduces risk of clinical depressive syndrome, 2)&#xD;
      yields better mood scores over time, compared to placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL is a randomized&#xD;
      clinical trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3&#xD;
      fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements in the&#xD;
      prevention of depression in older adults. Existing data from laboratory studies,&#xD;
      epidemiologic research, limited clinical trials research suggest that these nutritional&#xD;
      agents may reduce risk of depression or improve mood, but large primary prevention trials&#xD;
      with adequate dosing and lengthy treatment durations in general populations are lacking.&#xD;
&#xD;
      Eligible participants will be assigned by chance (like a coin toss) to one of four groups:&#xD;
      (1) daily vitamin D3 and omega-3; (2) daily vitamin D3 and omega-3 placebo; (3) daily vitamin&#xD;
      D placebo and omega-3; or (4) daily vitamin D placebo and omega-3 placebo. Participants have&#xD;
      an equal chance of being assigned to any of these four groups and a 3 out of 4 chance of&#xD;
      getting at least one active agent.&#xD;
&#xD;
      Participants in all groups will take two pills each day -- one softgel that contains either&#xD;
      vitamin D3 or vitamin D placebo and one capsule that contains either omega-3 or omega-3&#xD;
      placebo. Participants will receive their study pills in convenient calendar packages via U.S.&#xD;
      mail.&#xD;
&#xD;
      Participants will also fill out a short (15-20 minute) questionnaire each year. The&#xD;
      questionnaire asks about health; lifestyle habits such as physical exercise, diet, and&#xD;
      smoking; use of medications and dietary supplements; family history of illness, and new&#xD;
      medical diagnoses. The questionnaire also includes specific questions pertaining to mood.&#xD;
      Occasionally, participants may receive a phone call from study staff to collect information&#xD;
      or to clarify responses on the questionnaire.&#xD;
&#xD;
      Primary aims of 1) reduction in risk of clinical depressive syndrome and 2) yielding of&#xD;
      better mood scores over time will be address in the full VITAL cohort of 20,000. Secondary&#xD;
      aims will be addressed in sub-set of participants. The secondary aims will address whether:&#xD;
      1) among a subset of 1,000 participants evaluated at a Clinical and Translational Science&#xD;
      Center (CTSC), the agents reduce risk of depression and yield better mood scores among&#xD;
      persons with known risk factors for late-life depression; 2) among a subset of 1,000&#xD;
      participants evaluated at a CTSC, the agents reduce risk of major depression and yield better&#xD;
      mood scores among persons with sub-syndromal depressive symptoms; 3) among all VITAL&#xD;
      participants, African-American race (African-Americans have high risk of Vitamin D&#xD;
      deficiency) modifies effects of vitamin D3 supplementation on late-life depression risk and&#xD;
      on mood scores; 4) among a subset of participants, baseline plasma levels of vitamin D and&#xD;
      omega-3 fatty acids are related to depression risk and/or modify agent effects.&#xD;
&#xD;
      Thus, VITAL-DEP will address simultaneously the impact of both vitamin D and fish oil for&#xD;
      universal, selective and indicated prevention of late-life depression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>July 2010</start_date>
  <completion_date type="Anticipated">February 2025</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</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>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With a Depression Event</measure>
    <time_frame>From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up</time_frame>
    <description>Depression syndrome will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (e.g., PHQ) items. This is an event outcome, where the depression event was defined as a new self-report of physician/clinician-diagnosed depression, treatment (medication and/or counseling) for depression, or presence of clinically relevant depressive symptoms (PHQ-8 total score &gt;=10 points) on the annual study questionnaires that were administered over a median 5.3 years of randomized treatment and follow-up. Participants were followed for the depression event until the occurrence of the endpoint, death, or the end of the trial, whichever came first. The Outcome Measure table shows the counts of depression events in each randomized group by treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mood Scores</measure>
    <time_frame>Baseline, follow-up year 1, follow-up year 2, follow-up year 3, follow-up year 4, and follow-up year 5</time_frame>
    <description>Mood scores are evaluated by the 8-item Patient Health Questionnaire (PHQ-8). The measured outcome was the total PHQ-8 score. The PHQ-8 includes items corresponding to the criteria for major depression. Each of the 8 items can be scored as 0, 1, 2, or 3 points (higher score means worse symptoms). The 8 items are summed to a total PHQ-8 score. The range for the PHQ-8 score is 0-24 points; higher scores denote worse mood or depressive symptoms. The PHQ-8 was measured annually at baseline and at up to 5 follow-up times (for a maximum of 6 time points). Data from all time points was used to determine the mean differences in change in mood scores over all follow-up by randomized treatment. Per protocol, the Statistical Analysis section shows the results for the primary outcome of mean difference in overall change in PHQ-8 scores comparing active and placebo groups (for each agent).</description>
  </primary_outcome>
  <other_outcome>
    <measure>Number of Participants With an Incident Depression Event</measure>
    <time_frame>From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up</time_frame>
    <description>Post-hoc Outcome. Incident Depression is defined as depression cases that occurred among those with no past history of depression as of baseline. Incident depression event was determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 &gt;=10 points).</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants With a Recurrent Depression Event</measure>
    <time_frame>From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up</time_frame>
    <description>Post-hoc Outcome. Recurrent depression is defined as depression cases that occurred among those with past history of depression, but not under treatment or active in the past 2 years as of baseline. Recurrent depression event will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 &gt;=10 points).</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">18353</enrollment>
  <condition>Depression</condition>
  <condition>Depressive Symptoms</condition>
  <condition>Mood</condition>
  <arm_group>
    <arm_group_label>Vitamin D + fish oil placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
Fish oil placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D placebo + fish oil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D placebo&#xD;
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>
  <arm_group>
    <arm_group_label>Vitamin D placebo + fish oil placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D placebo&#xD;
Fish oil placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D + fish oil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
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>
  <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>
  <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>
    <other_name>fish oil</other_name>
  </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>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D 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>
  <eligibility>
    <criteria>
      <textblock>
        Participants in VITAL (NCT 01169259) who meet the following criteria are eligible to&#xD;
        participate in this ancillary study. These are the criteria specific for testing of the&#xD;
        primary aims in the VITAL-DEP ancillary study:&#xD;
&#xD;
          -  no current significant depressive symptoms&#xD;
&#xD;
          -  no core major depressive disorder symptoms for a period of two or more weeks in the&#xD;
             past two years&#xD;
&#xD;
          -  no history of alcohol and/or substance abuse disorder active in the past 12 months,&#xD;
             schizophrenia or other primary psychotic disorder, bipolar disorder, post-traumatic&#xD;
             stress disorder or obsessive-compulsive disorder&#xD;
&#xD;
          -  no current psychotherapy or current use of psychotropics (including non-prescription&#xD;
             agents for the treatment of mood disorders), except for limited use of mild&#xD;
             sedatives/hypnotics&#xD;
&#xD;
          -  no history of major neurologic disorder or delirium episode in the past 12 months&#xD;
&#xD;
          -  no history of clinical (i.e., overt and not sub-clinical) hypothyroidism diagnosis&#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>Olivia I Okereke, MD, SM</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>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.vitalstudy.org</url>
    <description>Welcome to the VITAL study website</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 24, 2012</study_first_submitted>
  <study_first_submitted_qc>September 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2012</study_first_posted>
  <results_first_submitted>December 30, 2022</results_first_submitted>
  <results_first_submitted_qc>February 17, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 14, 2023</results_first_posted>
  <last_update_submitted>February 17, 2023</last_update_submitted>
  <last_update_submitted_qc>February 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 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>Olivia Okereke</investigator_full_name>
    <investigator_title>Olivia I. Okereke, MD, SM, Principal Investigator, Brigham and Women's Hospital</investigator_title>
  </responsible_party>
  <keyword>Depression</keyword>
  <keyword>Depressive Symptoms</keyword>
  <keyword>Mood</keyword>
  <keyword>Geriatric</keyword>
  <keyword>Prevention</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 27, 2012</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/35/NCT01696435/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>401605 initially screened; 39430 eligible to enter run-in; 25871 eligible for randomization; 2x2 factorial design: 12927 assigned to active vit D (of these, 6463 assigned to active omega-3 FAs and 6464 to placebo omega-3 FAs) &amp; 12944 assigned to placebo vit D (of these, 6470 assigned to active omega-3 FAs and 6474 to placebo omega-3 FAs). Additional 7518 excluded per VITAL-DEP eligibility criteria; 18353 at risk for depression during follow-up.</recruitment_details>
      <pre_assignment_details>The trial included a 3-month placebo run-in period to select participants likely to have adequate compliance. Only individuals who reported taking at least 2/3 of their study pills during the placebo run-in and met other eligibility criteria were randomized into the trial.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Vitamin D + Fish Oil Placebo</title>
          <description>Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
Fish oil placebo&#xD;
vitamin D3: Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
Fish oil placebo: Fish oil placebo</description>
        </group>
        <group group_id="P2">
          <title>Vitamin D Placebo + Fish Oil</title>
          <description>Vitamin D placebo&#xD;
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])&#xD;
omega-3 fatty acids (fish oil): 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]).&#xD;
Vitamin D placebo: Vitamin D placebo</description>
        </group>
        <group group_id="P3">
          <title>Vitamin D Placebo + Fish Oil Placebo</title>
          <description>Vitamin D placebo&#xD;
Fish oil placebo&#xD;
Fish oil placebo: Fish oil placebo&#xD;
Vitamin D placebo: Vitamin D placebo</description>
        </group>
        <group group_id="P4">
          <title>Vitamin D + Fish Oil</title>
          <description>Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
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])&#xD;
vitamin D3: Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
omega-3 fatty acids (fish oil): 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>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4573"/>
                <participants group_id="P2" count="4563"/>
                <participants group_id="P3" count="4609"/>
                <participants group_id="P4" count="4608"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4573"/>
                <participants group_id="P2" count="4563"/>
                <participants group_id="P3" count="4609"/>
                <participants group_id="P4" count="4608"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vitamin D + Fish Oil Placebo</title>
          <description>Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
Fish oil placebo&#xD;
vitamin D3: Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
Fish oil placebo: Fish oil placebo</description>
        </group>
        <group group_id="B2">
          <title>Vitamin D Placebo + Fish Oil</title>
          <description>Vitamin D placebo&#xD;
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])&#xD;
omega-3 fatty acids (fish oil): 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]).&#xD;
Vitamin D placebo: Vitamin D placebo</description>
        </group>
        <group group_id="B3">
          <title>Vitamin D Placebo + Fish Oil Placebo</title>
          <description>Vitamin D placebo&#xD;
Fish oil placebo&#xD;
Fish oil placebo: Fish oil placebo&#xD;
Vitamin D placebo: Vitamin D placebo</description>
        </group>
        <group group_id="B4">
          <title>Vitamin D + Fish Oil</title>
          <description>Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
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])&#xD;
vitamin D3: Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
omega-3 fatty acids (fish oil): 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>
        </group>
        <group group_id="B5">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4573"/>
            <count group_id="B2" value="4563"/>
            <count group_id="B3" value="4609"/>
            <count group_id="B4" value="4608"/>
            <count group_id="B5" value="18353"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1642"/>
                    <measurement group_id="B2" value="1657"/>
                    <measurement group_id="B3" value="1674"/>
                    <measurement group_id="B4" value="1644"/>
                    <measurement group_id="B5" value="6617"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2931"/>
                    <measurement group_id="B2" value="2906"/>
                    <measurement group_id="B3" value="2935"/>
                    <measurement group_id="B4" value="2964"/>
                    <measurement group_id="B5" value="11736"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="67.5" spread="7.0"/>
                    <measurement group_id="B2" value="67.4" spread="7.1"/>
                    <measurement group_id="B3" value="67.5" spread="7.0"/>
                    <measurement group_id="B4" value="67.5" spread="7.1"/>
                    <measurement group_id="B5" value="67.5" spread="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2261"/>
                    <measurement group_id="B2" value="2218"/>
                    <measurement group_id="B3" value="2265"/>
                    <measurement group_id="B4" value="2279"/>
                    <measurement group_id="B5" value="9023"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2312"/>
                    <measurement group_id="B2" value="2345"/>
                    <measurement group_id="B3" value="2344"/>
                    <measurement group_id="B4" value="2329"/>
                    <measurement group_id="B5" value="9330"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Total</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4573"/>
                    <measurement group_id="B2" value="4563"/>
                    <measurement group_id="B3" value="4609"/>
                    <measurement group_id="B4" value="4608"/>
                    <measurement group_id="B5" value="18353"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Hispanic White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3255"/>
                    <measurement group_id="B2" value="3266"/>
                    <measurement group_id="B3" value="3279"/>
                    <measurement group_id="B4" value="3297"/>
                    <measurement group_id="B5" value="13097"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African-American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="855"/>
                    <measurement group_id="B2" value="833"/>
                    <measurement group_id="B3" value="869"/>
                    <measurement group_id="B4" value="850"/>
                    <measurement group_id="B5" value="3407"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic (not Black or African-American)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="185"/>
                    <measurement group_id="B2" value="170"/>
                    <measurement group_id="B3" value="176"/>
                    <measurement group_id="B4" value="177"/>
                    <measurement group_id="B5" value="708"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian or Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66"/>
                    <measurement group_id="B2" value="72"/>
                    <measurement group_id="B3" value="78"/>
                    <measurement group_id="B4" value="78"/>
                    <measurement group_id="B5" value="294"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native American or Alaskan Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="33"/>
                    <measurement group_id="B4" value="41"/>
                    <measurement group_id="B5" value="150"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other/Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="175"/>
                    <measurement group_id="B2" value="183"/>
                    <measurement group_id="B3" value="174"/>
                    <measurement group_id="B4" value="165"/>
                    <measurement group_id="B5" value="697"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4573"/>
                    <measurement group_id="B2" value="4563"/>
                    <measurement group_id="B3" value="4609"/>
                    <measurement group_id="B4" value="4608"/>
                    <measurement group_id="B5" value="18353"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With a Depression Event</title>
        <description>Depression syndrome will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (e.g., PHQ) items. This is an event outcome, where the depression event was defined as a new self-report of physician/clinician-diagnosed depression, treatment (medication and/or counseling) for depression, or presence of clinically relevant depressive symptoms (PHQ-8 total score &gt;=10 points) on the annual study questionnaires that were administered over a median 5.3 years of randomized treatment and follow-up. Participants were followed for the depression event until the occurrence of the endpoint, death, or the end of the trial, whichever came first. The Outcome Measure table shows the counts of depression events in each randomized group by treatment.</description>
        <time_frame>From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up</time_frame>
        <population>Analysis population reflects the randomized groups by treatment agents, as all published analyses per protocol were conducted comparing active treatment to placebo. These groups were: n=9181 randomized to active vitamin D and n=9172 randomized to vitamin D placebo; n=9171 randomized to active fish oil and n=9182 randomized to fish oil placebo. Per intervention results are presented for active vitamin D vs. matching vitamin D placebo and for active fish oil vs. matching fish oil placebo.</population>
        <group_list>
          <group group_id="O1">
            <title>Active Vitamin D</title>
            <description>Vitamin D3: Vitamin D3 (cholecalciferol), one 2000 IU capsule per day</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D Placebo</title>
            <description>Vitamin D placebo: Vitamin D placebo, one capsule per day</description>
          </group>
          <group group_id="O3">
            <title>Active Fish Oil</title>
            <description>Fish oil: Omacor, one 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>
          </group>
          <group group_id="O4">
            <title>Fish Oil Placebo</title>
            <description>Fish oil placebo: Fish oil placebo, one capsule per day</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Depression Event</title>
          <description>Depression syndrome will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (e.g., PHQ) items. This is an event outcome, where the depression event was defined as a new self-report of physician/clinician-diagnosed depression, treatment (medication and/or counseling) for depression, or presence of clinically relevant depressive symptoms (PHQ-8 total score &gt;=10 points) on the annual study questionnaires that were administered over a median 5.3 years of randomized treatment and follow-up. Participants were followed for the depression event until the occurrence of the endpoint, death, or the end of the trial, whichever came first. The Outcome Measure table shows the counts of depression events in each randomized group by treatment.</description>
          <population>Analysis population reflects the randomized groups by treatment agents, as all published analyses per protocol were conducted comparing active treatment to placebo. These groups were: n=9181 randomized to active vitamin D and n=9172 randomized to vitamin D placebo; n=9171 randomized to active fish oil and n=9182 randomized to fish oil placebo. Per intervention results are presented for active vitamin D vs. matching vitamin D placebo and for active fish oil vs. matching fish oil placebo.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9181"/>
                <count group_id="O2" value="9172"/>
                <count group_id="O3" value="9171"/>
                <count group_id="O4" value="9182"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="609"/>
                    <measurement group_id="O2" value="625"/>
                    <measurement group_id="O3" value="651"/>
                    <measurement group_id="O4" value="583"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.62</p_value>
            <p_value_desc>P-value was not adjusted for multiple comparisons. A priori, two-sided tests with an alpha level of 0.025 were used to account for the 2 co-primary outcomes (depression event and mood scores).</p_value_desc>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>.97</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>.87</ci_lower_limit>
            <ci_upper_limit>1.09</ci_upper_limit>
            <estimate_desc>Active treatment vs. Placebo comparison</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.03</p_value>
            <p_value_desc>P-value was not adjusted for multiple comparisons. A priori, two-sided tests with an alpha level of 0.025 were used to account for the 2 co-primary outcomes (depression event and mood scores).</p_value_desc>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.13</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.01</ci_lower_limit>
            <ci_upper_limit>1.26</ci_upper_limit>
            <estimate_desc>Active treatment vs. Placebo comparison</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mood Scores</title>
        <description>Mood scores are evaluated by the 8-item Patient Health Questionnaire (PHQ-8). The measured outcome was the total PHQ-8 score. The PHQ-8 includes items corresponding to the criteria for major depression. Each of the 8 items can be scored as 0, 1, 2, or 3 points (higher score means worse symptoms). The 8 items are summed to a total PHQ-8 score. The range for the PHQ-8 score is 0-24 points; higher scores denote worse mood or depressive symptoms. The PHQ-8 was measured annually at baseline and at up to 5 follow-up times (for a maximum of 6 time points). Data from all time points was used to determine the mean differences in change in mood scores over all follow-up by randomized treatment. Per protocol, the Statistical Analysis section shows the results for the primary outcome of mean difference in overall change in PHQ-8 scores comparing active and placebo groups (for each agent).</description>
        <time_frame>Baseline, follow-up year 1, follow-up year 2, follow-up year 3, follow-up year 4, and follow-up year 5</time_frame>
        <population>Analysis population reflects the randomized groups by treatment agents, as all published analyses per protocol were conducted comparing active treatment to placebo. These were n=9181 randomized to active vitamin D; n=9172 randomized to vitamin D placebo; n=9171 randomized to active fish oil; n=9182 randomized to fish oil placebo. Per intervention results are presented for active treatment vs placebo. Each row shows exact number of participants providing responses to the PHQ-8 at that timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Active Vitamin D</title>
            <description>Vitamin D3: Vitamin D3 (cholecalciferol), one 2000 IU capsule per day</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D Placebo</title>
            <description>Vitamin D placebo: Vitamin D placebo, one capsule per day</description>
          </group>
          <group group_id="O3">
            <title>Active Fish Oil</title>
            <description>Fish oil: Omacor, one 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>
          </group>
          <group group_id="O4">
            <title>Fish Oil Placebo</title>
            <description>Fish oil placebo: Fish oil placebo, one capsule per day</description>
          </group>
        </group_list>
        <measure>
          <title>Mood Scores</title>
          <description>Mood scores are evaluated by the 8-item Patient Health Questionnaire (PHQ-8). The measured outcome was the total PHQ-8 score. The PHQ-8 includes items corresponding to the criteria for major depression. Each of the 8 items can be scored as 0, 1, 2, or 3 points (higher score means worse symptoms). The 8 items are summed to a total PHQ-8 score. The range for the PHQ-8 score is 0-24 points; higher scores denote worse mood or depressive symptoms. The PHQ-8 was measured annually at baseline and at up to 5 follow-up times (for a maximum of 6 time points). Data from all time points was used to determine the mean differences in change in mood scores over all follow-up by randomized treatment. Per protocol, the Statistical Analysis section shows the results for the primary outcome of mean difference in overall change in PHQ-8 scores comparing active and placebo groups (for each agent).</description>
          <population>Analysis population reflects the randomized groups by treatment agents, as all published analyses per protocol were conducted comparing active treatment to placebo. These were n=9181 randomized to active vitamin D; n=9172 randomized to vitamin D placebo; n=9171 randomized to active fish oil; n=9182 randomized to fish oil placebo. Per intervention results are presented for active treatment vs placebo. Each row shows exact number of participants providing responses to the PHQ-8 at that timepoint.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9181"/>
                <count group_id="O2" value="9172"/>
                <count group_id="O3" value="9171"/>
                <count group_id="O4" value="9182"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline adjusted mean</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9181"/>
                    <count group_id="O2" value="9172"/>
                    <count group_id="O3" value="9171"/>
                    <count group_id="O4" value="9182"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.08" lower_limit="1.05" upper_limit="1.11"/>
                    <measurement group_id="O2" value="1.13" lower_limit="1.09" upper_limit="1.16"/>
                    <measurement group_id="O3" value="1.09" lower_limit="1.06" upper_limit="1.13"/>
                    <measurement group_id="O4" value="1.11" lower_limit="1.08" upper_limit="1.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean change at Year 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8534"/>
                    <count group_id="O2" value="8486"/>
                    <count group_id="O3" value="8471"/>
                    <count group_id="O4" value="8549"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.03" lower_limit="-0.01" upper_limit="0.07"/>
                    <measurement group_id="O2" value="0.03" lower_limit="0.00" upper_limit="0.07"/>
                    <measurement group_id="O3" value="0.05" lower_limit="0.01" upper_limit="0.09"/>
                    <measurement group_id="O4" value="0.01" lower_limit="-0.02" upper_limit="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean change at Year 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8381"/>
                    <count group_id="O2" value="8344"/>
                    <count group_id="O3" value="8354"/>
                    <count group_id="O4" value="8371"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.07" lower_limit="0.03" upper_limit="0.11"/>
                    <measurement group_id="O2" value="0.04" lower_limit="0.00" upper_limit="0.08"/>
                    <measurement group_id="O3" value="0.07" lower_limit="0.03" upper_limit="0.11"/>
                    <measurement group_id="O4" value="0.04" lower_limit="0.00" upper_limit="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean change at Year 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8176"/>
                    <count group_id="O2" value="8112"/>
                    <count group_id="O3" value="8116"/>
                    <count group_id="O4" value="8172"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.09" lower_limit="0.05" upper_limit="0.13"/>
                    <measurement group_id="O2" value="0.07" lower_limit="0.03" upper_limit="0.12"/>
                    <measurement group_id="O3" value="0.10" lower_limit="0.06" upper_limit="0.15"/>
                    <measurement group_id="O4" value="0.06" lower_limit="0.02" upper_limit="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean change at Year 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7763"/>
                    <count group_id="O2" value="7603"/>
                    <count group_id="O3" value="7676"/>
                    <count group_id="O4" value="7690"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" lower_limit="0.02" upper_limit="0.10"/>
                    <measurement group_id="O2" value="0.07" lower_limit="0.03" upper_limit="0.11"/>
                    <measurement group_id="O3" value="0.08" lower_limit="0.04" upper_limit="0.12"/>
                    <measurement group_id="O4" value="0.05" lower_limit="0.01" upper_limit="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean change at Year 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5316"/>
                    <count group_id="O2" value="5231"/>
                    <count group_id="O3" value="5295"/>
                    <count group_id="O4" value="5252"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.20" lower_limit="0.15" upper_limit="0.25"/>
                    <measurement group_id="O2" value="0.16" lower_limit="0.11" upper_limit="0.22"/>
                    <measurement group_id="O3" value="0.18" lower_limit="0.13" upper_limit="0.23"/>
                    <measurement group_id="O4" value="0.19" lower_limit="0.13" upper_limit="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Test of whether the mean difference in change comparing the treatment groups is different than zero. See full SAP for all details.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.01</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.04</ci_lower_limit>
            <ci_upper_limit>0.05</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Test of whether the mean difference in change comparing the treatment groups is different than zero. See full SAP for all details.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.01</ci_lower_limit>
            <ci_upper_limit>0.07</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With an Incident Depression Event</title>
        <description>Post-hoc Outcome. Incident Depression is defined as depression cases that occurred among those with no past history of depression as of baseline. Incident depression event was determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 &gt;=10 points).</description>
        <time_frame>From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up</time_frame>
        <population>Post-hoc Outcome. Incident Depression is defined as depression cases that occurred among those with no past history of depression as of baseline. Incident depression event was determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 &gt;=10 points). Among the n=18,353 participants randomized, there were n=16657 without a history of depression at baseline and therefore at risk for incident depression.</population>
        <group_list>
          <group group_id="O1">
            <title>Active Vitamin D</title>
            <description>Vitamin D3: Vitamin D3 (cholecalciferol), one 2000 IU capsule per day</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D Placebo</title>
            <description>Vitamin D placebo: Vitamin D placebo, one capsule per day</description>
          </group>
          <group group_id="O3">
            <title>Active Fish Oil</title>
            <description>Fish oil: Omacor, one 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>
          </group>
          <group group_id="O4">
            <title>Fish Oil Placebo</title>
            <description>Fish oil placebo: Fish oil placebo, one capsule per day</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With an Incident Depression Event</title>
          <description>Post-hoc Outcome. Incident Depression is defined as depression cases that occurred among those with no past history of depression as of baseline. Incident depression event was determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 &gt;=10 points).</description>
          <population>Post-hoc Outcome. Incident Depression is defined as depression cases that occurred among those with no past history of depression as of baseline. Incident depression event was determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 &gt;=10 points). Among the n=18,353 participants randomized, there were n=16657 without a history of depression at baseline and therefore at risk for incident depression.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8350"/>
                <count group_id="O2" value="8307"/>
                <count group_id="O3" value="8322"/>
                <count group_id="O4" value="8335"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="459"/>
                    <measurement group_id="O2" value="461"/>
                    <measurement group_id="O3" value="493"/>
                    <measurement group_id="O4" value="427"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.88</p_value>
            <p_value_desc>P-value not adjusted for multiple comparisons. This outcome was not a pre-specified primary outcome and results are to be interpreted with caution.</p_value_desc>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.99</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.87</ci_lower_limit>
            <ci_upper_limit>1.13</ci_upper_limit>
            <estimate_desc>Active treatment vs. Placebo comparison</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.02</p_value>
            <p_value_desc>P-value not adjusted for multiple comparisons. This outcome was not a pre-specified primary outcome and results are to be interpreted with caution.</p_value_desc>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.17</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.03</ci_lower_limit>
            <ci_upper_limit>1.33</ci_upper_limit>
            <estimate_desc>Active treatment vs. Placebo comparison</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With a Recurrent Depression Event</title>
        <description>Post-hoc Outcome. Recurrent depression is defined as depression cases that occurred among those with past history of depression, but not under treatment or active in the past 2 years as of baseline. Recurrent depression event will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 &gt;=10 points).</description>
        <time_frame>From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up</time_frame>
        <population>Post-hoc Outcome. Recurrent Depression is defined as depression cases that occurred among those with past history of depression, but not active in the past 2 years as of baseline. Recurrent depression event will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 &gt;=10 points). Among n=18,353 randomized, n=1696 were eligible for recurrent depression.</population>
        <group_list>
          <group group_id="O1">
            <title>Active Vitamin D</title>
            <description>Vitamin D3: Vitamin D3 (cholecalciferol), one 2000 IU capsule per day</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D Placebo</title>
            <description>Vitamin D placebo: Vitamin D placebo, one capsule per day</description>
          </group>
          <group group_id="O3">
            <title>Active Fish Oil</title>
            <description>Fish oil: Omacor, one 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>
          </group>
          <group group_id="O4">
            <title>Fish Oil Placebo</title>
            <description>Fish oil placebo: Fish oil placebo, one capsule per day</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Recurrent Depression Event</title>
          <description>Post-hoc Outcome. Recurrent depression is defined as depression cases that occurred among those with past history of depression, but not under treatment or active in the past 2 years as of baseline. Recurrent depression event will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 &gt;=10 points).</description>
          <population>Post-hoc Outcome. Recurrent Depression is defined as depression cases that occurred among those with past history of depression, but not active in the past 2 years as of baseline. Recurrent depression event will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 &gt;=10 points). Among n=18,353 randomized, n=1696 were eligible for recurrent depression.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="831"/>
                <count group_id="O2" value="865"/>
                <count group_id="O3" value="849"/>
                <count group_id="O4" value="847"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="150"/>
                    <measurement group_id="O2" value="164"/>
                    <measurement group_id="O3" value="158"/>
                    <measurement group_id="O4" value="156"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>P-value not adjusted for multiple comparisons. This outcome was not a pre-specified primary outcome and results are to be interpreted with caution.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.67</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.95</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.76</ci_lower_limit>
            <ci_upper_limit>1.19</ci_upper_limit>
            <estimate_desc>Active treatment vs. Placebo comparison</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>P-value not adjusted for multiple comparisons. This outcome was not a pre-specified primary outcome and results are to be interpreted with caution.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.88</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.02</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.82</ci_lower_limit>
            <ci_upper_limit>1.27</ci_upper_limit>
            <estimate_desc>Active treatment vs. Placebo comparison</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected over the entire randomized treatment and follow-up period, which was a median of 5.3 years. VITAL-DEP is an ancillary study of the VITAL trial. For total adverse events reported by the parent VITAL trial, please see Results reported by VITAL, NCT01169259.</time_frame>
      <desc>Results for adverse events are reported by each of the 4 factorial arms of the trial.</desc>
      <group_list>
        <group group_id="E1">
          <title>Vitamin D + Fish Oil Placebo</title>
          <description>Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
Fish oil placebo: Fish oil placebo, one capsule per day</description>
        </group>
        <group group_id="E2">
          <title>Vitamin D Placebo + Fish Oil</title>
          <description>Vitamin D placebo: Vitamin D3 placebo, one capsule per day&#xD;
Fish oil: Omacor, one 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>
        </group>
        <group group_id="E3">
          <title>Vitamin D Placebo + Fish Oil Placebo</title>
          <description>Vitamin D placebo: Vitamin D3 placebo, one capsule per day&#xD;
Fish oil placebo: Fish oil placebo, one capsule per day</description>
        </group>
        <group group_id="E4">
          <title>Vitamin D + Fish Oil</title>
          <description>Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day&#xD;
Fish oil: Omacor, one 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>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="153" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="152" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="133" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="153" subjects_at_risk="4608"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="545" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="569" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="570" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="549" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal Bleeding</sub_title>
                <counts group_id="E1" subjects_affected="111" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="133" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="135" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="107" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="47" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="49" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="53" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="42" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Invasive cancer of any type</sub_title>
                <counts group_id="E1" subjects_affected="281" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="301" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="291" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="312" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicide</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Major cardiovascular event</sub_title>
                <counts group_id="E1" subjects_affected="144" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="129" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="126" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="120" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2803" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="2789" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="2876" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="2825" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <description>Blood in urine</description>
                <counts group_id="E1" subjects_affected="319" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="293" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="318" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="333" subjects_at_risk="4608"/>
              </event>
              <event>
                <sub_title>Easy bruising</sub_title>
                <counts group_id="E1" subjects_affected="1167" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="1124" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="1141" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="1152" subjects_at_risk="4608"/>
              </event>
              <event>
                <sub_title>Frequent nosebleeds</sub_title>
                <counts group_id="E1" subjects_affected="159" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="158" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="163" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="159" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperparathyroidism or parathyroid condition</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="27" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Stomach upset or pain</sub_title>
                <counts group_id="E1" subjects_affected="1594" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="1616" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="1625" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="1615" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Kidney stones</sub_title>
                <counts group_id="E1" subjects_affected="172" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="131" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="163" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="158" subjects_at_risk="4608"/>
              </event>
              <event>
                <sub_title>Kidney failure</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="29" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="19" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin rash</sub_title>
                <counts group_id="E1" subjects_affected="1105" subjects_at_risk="4573"/>
                <counts group_id="E2" subjects_affected="1169" subjects_at_risk="4563"/>
                <counts group_id="E3" subjects_affected="1184" subjects_at_risk="4609"/>
                <counts group_id="E4" subjects_affected="1124" subjects_at_risk="4608"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Olivia Okereke/Study Principal Investigator</name_or_title>
      <organization>Massachusetts General Hospital</organization>
      <phone>(617) 726-2000</phone>
      <email>olivia.okereke@mgh.harvard.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01696435
org study id: 2010-P-001881
secondary id: R01MH091448
nct id: NCT01696435
lead sponsor: 
collaborator: 
has dmc: Yes
The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is an ongoing 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 whether vitamin D or fish oil: 1) reduces risk of clinical depressive syndrome, 2)
      yields better mood scores over time, compared to placebo.
VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL is a randomized
      clinical trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3
      fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements in the
      prevention of depression in older adults. Existing data from laboratory studies,
      epidemiologic research, limited clinical trials research suggest that these nutritional
      agents may reduce risk of depression or improve mood, but large primary prevention trials
      with adequate dosing and lengthy treatment durations in general populations are lacking.

      Eligible participants will be assigned by chance (like a coin toss) to one of four groups:
      (1) daily vitamin D3 and omega-3; (2) daily vitamin D3 and omega-3 placebo; (3) daily vitamin
      D placebo and omega-3; or (4) daily vitamin D placebo and omega-3 placebo. Participants have
      an equal chance of being assigned to any of these four groups and a 3 out of 4 chance of
      getting at least one active agent.

      Participants in all groups will take two pills each day -- one softgel that contains either
      vitamin D3 or vitamin D placebo and one capsule that contains either omega-3 or omega-3
      placebo. Participants will receive their study pills in convenient calendar packages via U.S.
      mail.

      Participants will also fill out a short (15-20 minute) questionnaire each year. The
      questionnaire asks about health; lifestyle habits such as physical exercise, diet, and
      smoking; use of medications and dietary supplements; family history of illness, and new
      medical diagnoses. The questionnaire also includes specific questions pertaining to mood.
      Occasionally, participants may receive a phone call from study staff to collect information
      or to clarify responses on the questionnaire.

      Primary aims of 1) reduction in risk of clinical depressive syndrome and 2) yielding of
      better mood scores over time will be address in the full VITAL cohort of 20,000. Secondary
      aims will be addressed in sub-set of participants. The secondary aims will address whether:
      1) among a subset of 1,000 participants evaluated at a Clinical and Translational Science
      Center (CTSC), the agents reduce risk of depression and yield better mood scores among
      persons with known risk factors for late-life depression; 2) among a subset of 1,000
      participants evaluated at a CTSC, the agents reduce risk of major depression and yield better
      mood scores among persons with sub-syndromal depressive symptoms; 3) among all VITAL
      participants, African-American race (African-Americans have high risk of Vitamin D
      deficiency) modifies effects of vitamin D3 supplementation on late-life depression risk and
      on mood scores; 4) among a subset of participants, baseline plasma levels of vitamin D and
      omega-3 fatty acids are related to depression risk and/or modify agent effects.

      Thus, VITAL-DEP will address simultaneously the impact of both vitamin D and fish oil for
      universal, selective and indicated prevention of late-life depression.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Number of Participants With a Depression Event
time frame: From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up
description: Depression syndrome will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (e.g., PHQ) items. This is an event outcome, where the depression event was defined as a new self-report of physician/clinician-diagnosed depression, treatment (medication and/or counseling) for depression, or presence of clinically relevant depressive symptoms (PHQ-8 total score >=10 points) on the annual study questionnaires that were administered over a median 5.3 years of randomized treatment and follow-up. Participants were followed for the depression event until the occurrence of the endpoint, death, or the end of the trial, whichever came first. The Outcome Measure table shows the counts of depression events in each randomized group by treatment.
measure: Mood Scores
time frame: Baseline, follow-up year 1, follow-up year 2, follow-up year 3, follow-up year 4, and follow-up year 5
description: Mood scores are evaluated by the 8-item Patient Health Questionnaire (PHQ-8). The measured outcome was the total PHQ-8 score. The PHQ-8 includes items corresponding to the criteria for major depression. Each of the 8 items can be scored as 0, 1, 2, or 3 points (higher score means worse symptoms). The 8 items are summed to a total PHQ-8 score. The range for the PHQ-8 score is 0-24 points; higher scores denote worse mood or depressive symptoms. The PHQ-8 was measured annually at baseline and at up to 5 follow-up times (for a maximum of 6 time points). Data from all time points was used to determine the mean differences in change in mood scores over all follow-up by randomized treatment. Per protocol, the Statistical Analysis section shows the results for the primary outcome of mean difference in overall change in PHQ-8 scores comparing active and placebo groups (for each agent).
measure: Number of Participants With an Incident Depression Event
time frame: From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up
description: Post-hoc Outcome. Incident Depression is defined as depression cases that occurred among those with no past history of depression as of baseline. Incident depression event was determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 >=10 points).
measure: Number of Participants With a Recurrent Depression Event
time frame: From date of randomization until the date of the occurrence of the endpoint, death, or the end of the trial, whichever came first, assessed up to a median of 5.3 years of follow-up
description: Post-hoc Outcome. Recurrent depression is defined as depression cases that occurred among those with past history of depression, but not under treatment or active in the past 2 years as of baseline. Recurrent depression event will be determined by presence of clinical diagnosis, treatment and/or above-threshold symptoms on mood questionnaire (i.e., PHQ-8 >=10 points).
arm group label: Vitamin D + fish oil placebo
arm group type: Active Comparator
description: Vitamin D3 (cholecalciferol), 2000 IU per day
Fish oil placebo
arm group label: Vitamin D placebo + fish oil
arm group type: Active Comparator
description: Vitamin D placebo
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 placebo + fish oil placebo
arm group type: Active Comparator
description: Vitamin D placebo
Fish oil placebo
arm group label: Vitamin D + fish oil
arm group type: Active Comparator
description: Vitamin D3 (cholecalciferol), 2000 IU per day
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])
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
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
other name: fish oil
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: Dietary Supplement
intervention name: Vitamin D placebo
description: Vitamin D placebo
arm group label: Vitamin D placebo + fish oil
arm group label: Vitamin D placebo + fish oil placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Olivia I Okereke, MD, SM
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
url: http://www.vitalstudy.org
description: Welcome to the VITAL study website
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Olivia Okereke
investigator title: Olivia I. Okereke, MD, SM, Principal Investigator, Brigham and Women's Hospital
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Vitamin D
mesh term: Ergocalciferols
mesh term: Cholecalciferol
mesh term: Vitamins
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 