<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/NCT01684722</url>
  </required_header>
  <id_info>
    <org_study_id>39113</org_study_id>
    <secondary_id>R01DK088762</secondary_id>
    <nct_id>NCT01684722</nct_id>
  </id_info>
  <brief_title>Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease</brief_title>
  <acronym>VITAL-DKD</acronym>
  <official_title>Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a randomized clinical trial in&#xD;
      20,000 U.S. men and women investigating whether taking daily dietary supplements of vitamin&#xD;
      D3 (2000 IU) or fish oil (1 gram of omega-3 fatty acids) 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 with a history&#xD;
      of diabetes and will examine whether vitamin D or fish oil prevents the development and&#xD;
      progression of diabetic kidney disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This ancillary study to the VITamin D and OmegA-3 TriaL (VITAL) will test whether vitamin D3,&#xD;
      omega-3 fatty acids, or both prevent the development and progression of diabetic kidney&#xD;
      disease (DKD). Persons with diabetes are at high risk of kidney disease. In 2005-2008, the&#xD;
      prevalence of DKD among people with type 2 diabetes in the United States was 34.5%. Moreover,&#xD;
      from 1988-1994 to 2005-2008, the prevalence of DKD in the United States grew 34% to 6.9&#xD;
      million people. DKD is both the leading cause of end stage renal disease in the developed&#xD;
      world and a potent amplifier of cardiovascular disease risk.&#xD;
&#xD;
      Vitamin D and omega-3 fatty acids are promising interventions for DKD prevention and&#xD;
      treatment, based on results of animal-experimental models and early human studies. Because&#xD;
      these interventions are relatively safe, inexpensive, and widely available, they may offer&#xD;
      opportunity to substantially reduce the burden of DKD in large populations. This VITAL&#xD;
      ancillary study will test whether vitamin D3 and/or omega-3 fatty acids prevent progression&#xD;
      of albuminuria and loss of glomerular filtration rate, two complementary manifestations of&#xD;
      DKD, over 3 years of treatment.&#xD;
&#xD;
      In VITAL, 20,000 participants will be randomly assigned in a 2x2 factorial design to vitamin&#xD;
      D3 (cholecalciferol) 2000 IU daily versus placebo, and to eicosapentaenoic acid 465 mg plus&#xD;
      docosahexaenoic acid 375 mg daily versus placebo, and followed for a mean of 5 years to&#xD;
      assess effects on cardiovascular disease and cancer events. This ancillary study will&#xD;
      identify and recruit a sub-cohort of VITAL participants with diabetes at baseline and&#xD;
      ascertain effects of study interventions on albuminuria and glomerular filtration rate in&#xD;
      this group. First morning voids will be collected at baseline and year 3 for measurement of&#xD;
      urine albumin-creatinine ratio. Blood samples will be collected simultaneously for&#xD;
      measurement of estimated glomerular filtration rate (using serum creatinine and cystatin C)&#xD;
      and other relevant biomarkers. This VITAL ancillary study is designed to determine whether&#xD;
      vitamin D3 and/or omega-3 fatty acids have causal and clinically relevant effects on the&#xD;
      development and progression of DKD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2010</start_date>
  <completion_date type="Actual">November 8, 2019</completion_date>
  <primary_completion_date type="Actual">November 8, 2019</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>Change in Estimated Glomerular Filtration Rate</measure>
    <time_frame>baseline to 5 years</time_frame>
    <description>GFR estimated from serum creatinine and cystatin C</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Urine Albumin Excretion</measure>
    <time_frame>baseline to 5 years</time_frame>
    <description>Change in urine albumin-creatinine ratio.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in C-reactive Protein</measure>
    <time_frame>baseline to 5 years</time_frame>
    <description>Changes in serum concentrations in CRP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Interleukin-6</measure>
    <time_frame>baseline to 5 years</time_frame>
    <description>Changes in serum concentrations in IL-6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in NT-proBNP</measure>
    <time_frame>baseline to 5 years</time_frame>
    <description>Changes in serum concentrations in NT-proBNP</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">1312</enrollment>
  <condition>Diabetes</condition>
  <arm_group>
    <arm_group_label>Vitamin D + fish oil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D and omega-3 fatty acids (fish oil)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D + fish oil placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin D and 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 and omega-3 fatty acids (fish oil)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D placebo + fish oil placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Vitamin D placebo and fish oil placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D</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>
  </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 D placebo</intervention_name>
    <description>Vitamin D3 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>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: Participants in VITAL (NCT 01169259) with a self-reported physician&#xD;
        diagnosis of diabetes are eligible to participate in this ancillary study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes&#xD;
&#xD;
          -  Diabetes only during pregnancy&#xD;
&#xD;
          -  Known cause of kidney disease other than diabetes&#xD;
&#xD;
          -  History of kidney transplantation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ian H de Boer, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Washington</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham 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>Vitamin D and Omega-3 Trial study website</description>
  </link>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <results_first_submitted>May 14, 2020</results_first_submitted>
  <results_first_submitted_qc>June 10, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">June 26, 2020</results_first_posted>
  <last_update_submitted>June 15, 2022</last_update_submitted>
  <last_update_submitted_qc>June 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>Ian deBoer</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>vitamin D3</keyword>
  <keyword>omega-3 fatty acids</keyword>
  <keyword>fish oil</keyword>
  <keyword>diabetes</keyword>
  <keyword>kidney disease</keyword>
  <keyword>albuminuria</keyword>
  <keyword>urine albumin excretion</keyword>
  <keyword>glomerular filtration rate</keyword>
  <keyword>diabetic kidney disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Diabetic Nephropathies</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>June 28, 2010</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/22/NCT01684722/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 17, 2010</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/22/NCT01684722/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Vitamin D + Fish Oil Placebo</title>
          <description>Vitamin D and fish oil placebo&#xD;
Vitamin D: 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 and omega-3 fatty acids (fish oil)&#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 D3 placebo</description>
        </group>
        <group group_id="P3">
          <title>Vitamin D Placebo + Fish Oil Placebo</title>
          <description>Vitamin D placebo and fish oil placebo&#xD;
Vitamin D placebo: Vitamin D3 placebo&#xD;
Fish oil placebo: Fish oil placebo</description>
        </group>
        <group group_id="P4">
          <title>Vitamin D + Fish Oil</title>
          <description>Vitamin D and omega-3 fatty acids (fish oil)&#xD;
Vitamin D: 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="333"/>
                <participants group_id="P2" count="289"/>
                <participants group_id="P3" count="320"/>
                <participants group_id="P4" count="370"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="236"/>
                <participants group_id="P2" count="212"/>
                <participants group_id="P3" count="226"/>
                <participants group_id="P4" count="260"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="97"/>
                <participants group_id="P2" count="77"/>
                <participants group_id="P3" count="94"/>
                <participants group_id="P4" count="110"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
                <participants group_id="P2" count="56"/>
                <participants group_id="P3" count="75"/>
                <participants group_id="P4" count="89"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="21"/>
                <participants group_id="P3" count="19"/>
                <participants group_id="P4" count="21"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vitamin D + Fish Oil Placebo</title>
          <description>Vitamin D and fish oil placebo&#xD;
Vitamin D: 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 and omega-3 fatty acids (fish oil)&#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 D3 placebo</description>
        </group>
        <group group_id="B3">
          <title>Vitamin D Placebo + Fish Oil Placebo</title>
          <description>Vitamin D placebo and fish oil placebo&#xD;
Vitamin D placebo: Vitamin D3 placebo&#xD;
Fish oil placebo: Fish oil placebo</description>
        </group>
        <group group_id="B4">
          <title>Vitamin D + Fish Oil</title>
          <description>Vitamin D and omega-3 fatty acids (fish oil)&#xD;
Vitamin D: 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="333"/>
            <count group_id="B2" value="289"/>
            <count group_id="B3" value="320"/>
            <count group_id="B4" value="370"/>
            <count group_id="B5" value="1312"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="67.4" spread="6.7"/>
                    <measurement group_id="B2" value="68.2" spread="6.7"/>
                    <measurement group_id="B3" value="67.5" spread="6.9"/>
                    <measurement group_id="B4" value="67.4" spread="7.3"/>
                    <measurement group_id="B5" value="67.6" spread="6.9"/>
                  </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="143"/>
                    <measurement group_id="B2" value="131"/>
                    <measurement group_id="B3" value="151"/>
                    <measurement group_id="B4" value="184"/>
                    <measurement group_id="B5" value="609"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="190"/>
                    <measurement group_id="B2" value="158"/>
                    <measurement group_id="B3" value="169"/>
                    <measurement group_id="B4" value="186"/>
                    <measurement group_id="B5" value="703"/>
                  </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>Non-Hispanic white</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="211"/>
                    <measurement group_id="B2" value="199"/>
                    <measurement group_id="B3" value="207"/>
                    <measurement group_id="B4" value="240"/>
                    <measurement group_id="B5" value="857"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Hispanic black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="71"/>
                    <measurement group_id="B4" value="73"/>
                    <measurement group_id="B5" value="278"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="20"/>
                    <measurement group_id="B5" value="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian/Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="13"/>
                    <measurement group_id="B5" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian/Alaska Natuve</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not available</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Estimated Glomerular Filtration Rate</title>
        <description>GFR estimated from serum creatinine and cystatin C</description>
        <time_frame>baseline to 5 years</time_frame>
        <population>Outcomes analyzed according to factorial assignments, without evidence of treatment interaction.</population>
        <group_list>
          <group group_id="O1">
            <title>Vitamin D</title>
            <description>Vitamin D 2000IU daily</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D Placebo</title>
            <description>Matching placebo daily</description>
          </group>
          <group group_id="O3">
            <title>Fish Oil</title>
            <description>Fish oil one capsule daily</description>
          </group>
          <group group_id="O4">
            <title>Fish Oil Placebo</title>
            <description>Matching placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Estimated Glomerular Filtration Rate</title>
          <description>GFR estimated from serum creatinine and cystatin C</description>
          <population>Outcomes analyzed according to factorial assignments, without evidence of treatment interaction.</population>
          <units>mL/min/1.73m2</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="703"/>
                <count group_id="O2" value="609"/>
                <count group_id="O3" value="659"/>
                <count group_id="O4" value="653"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.3" lower_limit="-13.4" upper_limit="-11.2"/>
                    <measurement group_id="O2" value="-13.1" lower_limit="-14.2" upper_limit="-11.9"/>
                    <measurement group_id="O3" value="-12.2" lower_limit="-13.3" upper_limit="-11.1"/>
                    <measurement group_id="O4" value="-13.1" lower_limit="-14.2" upper_limit="-12.0"/>
                  </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>0.25</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.7</ci_lower_limit>
            <ci_upper_limit>2.5</ci_upper_limit>
          </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>0.27</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.7</ci_lower_limit>
            <ci_upper_limit>2.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Urine Albumin Excretion</title>
        <description>Change in urine albumin-creatinine ratio.</description>
        <time_frame>baseline to 5 years</time_frame>
        <population>Outcomes analyzed according to factorial assignments, without evidence of treatment interaction.</population>
        <group_list>
          <group group_id="O1">
            <title>Vitamin D</title>
            <description>Vitamin D 2000IU daily</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D Placebo</title>
            <description>Matching placebo daily</description>
          </group>
          <group group_id="O3">
            <title>Fish Oil</title>
            <description>Fish oil one capsule daily</description>
          </group>
          <group group_id="O4">
            <title>Fish Oil Placebo</title>
            <description>Matching placebo daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Urine Albumin Excretion</title>
          <description>Change in urine albumin-creatinine ratio.</description>
          <population>Outcomes analyzed according to factorial assignments, without evidence of treatment interaction.</population>
          <units>geometric mean ratio</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="703"/>
                <count group_id="O2" value="609"/>
                <count group_id="O3" value="659"/>
                <count group_id="O4" value="653"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.97" lower_limit="2.66" upper_limit="3.32"/>
                    <measurement group_id="O2" value="3.02" lower_limit="2.70" upper_limit="3.38"/>
                    <measurement group_id="O3" value="2.94" lower_limit="2.62" upper_limit="3.30"/>
                    <measurement group_id="O4" value="3.05" lower_limit="2.74" upper_limit="3.40"/>
                  </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>0.90</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Ratio of change from baseline, active to</param_type>
            <param_value>0.99</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.84</ci_lower_limit>
            <ci_upper_limit>1.17</ci_upper_limit>
          </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>0.64</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Ratio of change from baseline, active to</param_type>
            <param_value>0.96</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.81</ci_lower_limit>
            <ci_upper_limit>1.14</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in C-reactive Protein</title>
        <description>Changes in serum concentrations in CRP</description>
        <time_frame>baseline to 5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin D</title>
            <description>Vitamin D3 (cholecalciferol), 2000 IU per day.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D Placebo</title>
            <description>Vitamin D placebo group</description>
          </group>
          <group group_id="O3">
            <title>Fish Oil</title>
            <description>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="O4">
            <title>Fish Oil Placebo</title>
            <description>Fish oil placebo group</description>
          </group>
        </group_list>
        <measure>
          <title>Change in C-reactive Protein</title>
          <description>Changes in serum concentrations in CRP</description>
          <units>mg/L</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="703"/>
                <count group_id="O2" value="609"/>
                <count group_id="O3" value="659"/>
                <count group_id="O4" value="653"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.93" spread="2.71"/>
                    <measurement group_id="O2" value="1.03" spread="3.03"/>
                    <measurement group_id="O3" value="0.90" spread="2.82"/>
                    <measurement group_id="O4" value="1.05" spread="2.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Interleukin-6</title>
        <description>Changes in serum concentrations in IL-6</description>
        <time_frame>baseline to 5 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin D</title>
            <description>Vitamin D3 (cholecalciferol), 2000 IU per day.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D Placebo</title>
            <description>Vitamin D placebo group</description>
          </group>
          <group group_id="O3">
            <title>Fish Oil</title>
            <description>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="O4">
            <title>Fish Oil Placebo</title>
            <description>Fish oil placebo group</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Interleukin-6</title>
          <description>Changes in serum concentrations in IL-6</description>
          <units>pg/ml</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="703"/>
                <count group_id="O2" value="609"/>
                <count group_id="O3" value="659"/>
                <count group_id="O4" value="653"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.04" spread="4.48"/>
                    <measurement group_id="O2" value="1.09" spread="4.44"/>
                    <measurement group_id="O3" value="1.10" spread="4.33"/>
                    <measurement group_id="O4" value="1.02" spread="4.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in NT-proBNP</title>
        <description>Changes in serum concentrations in NT-proBNP</description>
        <time_frame>baseline to 5 years</time_frame>
        <population>2x2 factorial design</population>
        <group_list>
          <group group_id="O1">
            <title>Vitamin D</title>
            <description>Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D Placebo</title>
            <description>Vitamin D placebo group</description>
          </group>
          <group group_id="O3">
            <title>Fish Oil</title>
            <description>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="O4">
            <title>Fish Oil Placebo</title>
            <description>Fish oil placebo group</description>
          </group>
        </group_list>
        <measure>
          <title>Change in NT-proBNP</title>
          <description>Changes in serum concentrations in NT-proBNP</description>
          <population>2x2 factorial design</population>
          <units>ng/l</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="703"/>
                <count group_id="O2" value="609"/>
                <count group_id="O3" value="659"/>
                <count group_id="O4" value="653"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.72" spread="3.24"/>
                    <measurement group_id="O2" value="1.38" spread="3.02"/>
                    <measurement group_id="O3" value="1.56" spread="3.07"/>
                    <measurement group_id="O4" value="1.54" spread="3.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to five years</time_frame>
      <desc>Only monitored safety conditions are reported.</desc>
      <group_list>
        <group group_id="E1">
          <title>Vitamin D + Fish Oil Placebo</title>
          <description>Vitamin D and fish oil placebo Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. Fish oil placebo: Fish oil placebo</description>
        </group>
        <group group_id="E2">
          <title>Vitamin D Placebo + Fish Oil</title>
          <description>Vitamin D placebo and omega-3 fatty acids (fish oil) 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 D3 placebo</description>
        </group>
        <group group_id="E3">
          <title>Vitamin D Placebo + Fish Oil Placebo</title>
          <description>Vitamin D placebo and fish oil placebo Vitamin D placebo: Vitamin D3 placebo Fish oil placebo: Fish oil placebo</description>
        </group>
        <group group_id="E4">
          <title>Vitamin D + Fish Oil</title>
          <description>Vitamin D and omega-3 fatty acids (fish oil) Vitamin D: Vitamin D3 (cholecalciferol), 2000 IU per day. 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>
      <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="19" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="21" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="59" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="45" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="44" subjects_at_risk="370"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Major CVD events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="18" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="16" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Cardiovascular death</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="370"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Malignant cancer</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Cancer death</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Malignant breast cancer</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Malignant prostate cancer</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Malignant colorectal cancer</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Stroke</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="370"/>
              </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="134" subjects_at_risk="333"/>
                <counts group_id="E2" subjects_affected="135" subjects_at_risk="289"/>
                <counts group_id="E3" subjects_affected="133" subjects_at_risk="320"/>
                <counts group_id="E4" subjects_affected="136" subjects_at_risk="370"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Easy bruising</sub_title>
                <counts group_id="E1" events="98" subjects_affected="98" subjects_at_risk="333"/>
                <counts group_id="E2" events="91" subjects_affected="91" subjects_at_risk="289"/>
                <counts group_id="E3" events="97" subjects_affected="97" subjects_at_risk="320"/>
                <counts group_id="E4" events="99" subjects_affected="99" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Frequent nosebleeds</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="333"/>
                <counts group_id="E2" events="13" subjects_affected="13" subjects_at_risk="289"/>
                <counts group_id="E3" events="17" subjects_affected="17" subjects_at_risk="320"/>
                <counts group_id="E4" events="11" subjects_affected="11" subjects_at_risk="370"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal bleeding</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="333"/>
                <counts group_id="E2" events="18" subjects_affected="18" subjects_at_risk="289"/>
                <counts group_id="E3" events="8" subjects_affected="8" subjects_at_risk="320"/>
                <counts group_id="E4" events="10" subjects_affected="10" subjects_at_risk="370"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="333"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="289"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="320"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Parathyroid condition</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="333"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="289"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="370"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Kidney stones</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="333"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="289"/>
                <counts group_id="E3" events="14" subjects_affected="14" subjects_at_risk="320"/>
                <counts group_id="E4" events="19" subjects_affected="19" subjects_at_risk="370"/>
              </event>
              <event>
                <sub_title>Blood in urine</sub_title>
                <counts group_id="E1" events="30" subjects_affected="30" subjects_at_risk="333"/>
                <counts group_id="E2" events="32" subjects_affected="32" subjects_at_risk="289"/>
                <counts group_id="E3" events="29" subjects_affected="29" subjects_at_risk="320"/>
                <counts group_id="E4" events="25" subjects_affected="25" subjects_at_risk="370"/>
              </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>Ian de Boer, MD, MS</name_or_title>
      <organization>University of Washington</organization>
      <phone>2066165403</phone>
      <email>deboer@u.washington.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/NCT01684722
org study id: 39113
secondary id: R01DK088762
nct id: NCT01684722
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) is a randomized clinical trial in
      20,000 U.S. men and women investigating whether taking daily dietary supplements of vitamin
      D3 (2000 IU) or fish oil (1 gram of omega-3 fatty acids) 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 with a history
      of diabetes and will examine whether vitamin D or fish oil prevents the development and
      progression of diabetic kidney disease.
This ancillary study to the VITamin D and OmegA-3 TriaL (VITAL) will test whether vitamin D3,
      omega-3 fatty acids, or both prevent the development and progression of diabetic kidney
      disease (DKD). Persons with diabetes are at high risk of kidney disease. In 2005-2008, the
      prevalence of DKD among people with type 2 diabetes in the United States was 34.5%. Moreover,
      from 1988-1994 to 2005-2008, the prevalence of DKD in the United States grew 34% to 6.9
      million people. DKD is both the leading cause of end stage renal disease in the developed
      world and a potent amplifier of cardiovascular disease risk.

      Vitamin D and omega-3 fatty acids are promising interventions for DKD prevention and
      treatment, based on results of animal-experimental models and early human studies. Because
      these interventions are relatively safe, inexpensive, and widely available, they may offer
      opportunity to substantially reduce the burden of DKD in large populations. This VITAL
      ancillary study will test whether vitamin D3 and/or omega-3 fatty acids prevent progression
      of albuminuria and loss of glomerular filtration rate, two complementary manifestations of
      DKD, over 3 years of treatment.

      In VITAL, 20,000 participants will be randomly assigned in a 2x2 factorial design to vitamin
      D3 (cholecalciferol) 2000 IU daily versus placebo, and to eicosapentaenoic acid 465 mg plus
      docosahexaenoic acid 375 mg daily versus placebo, and followed for a mean of 5 years to
      assess effects on cardiovascular disease and cancer events. This ancillary study will
      identify and recruit a sub-cohort of VITAL participants with diabetes at baseline and
      ascertain effects of study interventions on albuminuria and glomerular filtration rate in
      this group. First morning voids will be collected at baseline and year 3 for measurement of
      urine albumin-creatinine ratio. Blood samples will be collected simultaneously for
      measurement of estimated glomerular filtration rate (using serum creatinine and cystatin C)
      and other relevant biomarkers. This VITAL ancillary study is designed to determine whether
      vitamin D3 and/or omega-3 fatty acids have causal and clinically relevant effects on the
      development and progression of DKD.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in Estimated Glomerular Filtration Rate
time frame: baseline to 5 years
description: GFR estimated from serum creatinine and cystatin C
measure: Change in Urine Albumin Excretion
time frame: baseline to 5 years
description: Change in urine albumin-creatinine ratio.
measure: Change in C-reactive Protein
time frame: baseline to 5 years
description: Changes in serum concentrations in CRP
measure: Change in Interleukin-6
time frame: baseline to 5 years
description: Changes in serum concentrations in IL-6
measure: Change in NT-proBNP
time frame: baseline to 5 years
description: Changes in serum concentrations in NT-proBNP
arm group label: Vitamin D + fish oil
arm group type: Active Comparator
description: Vitamin D and omega-3 fatty acids (fish oil)
arm group label: Vitamin D + fish oil placebo
arm group type: Active Comparator
description: Vitamin D and fish oil placebo
arm group label: Vitamin D placebo + fish oil
arm group type: Active Comparator
description: Vitamin D placebo and omega-3 fatty acids (fish oil)
arm group label: Vitamin D placebo + fish oil placebo
arm group type: Placebo Comparator
description: Vitamin D placebo and fish oil placebo
intervention type: Dietary Supplement
intervention name: Vitamin D
description: Vitamin D3 (cholecalciferol), 2000 IU per day.
arm group label: Vitamin D + fish oil
arm group label: Vitamin D + 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 D placebo
description: Vitamin D3 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
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Ian H de Boer, MD, MS
role: Principal Investigator
affiliation: University of Washington
facility: 
country: United States
url: http://www.vitalstudy.org/
description: Vitamin D and Omega-3 Trial study website
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: Ian deBoer
investigator title: Associate Professor
mesh term: Kidney Diseases
mesh term: Diabetic Nephropathies
mesh term: Vitamin D
mesh term: Ergocalciferols
mesh term: Cholecalciferol
mesh term: Vitamins
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 