<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/NCT01689779</url>
  </required_header>
  <id_info>
    <org_study_id>2012P001852</org_study_id>
    <nct_id>NCT01689779</nct_id>
  </id_info>
  <brief_title>High Dose Preoperative Cholecalciferol Supplementation and Perioperative Vitamin D Status</brief_title>
  <official_title>Effect of High-dose Cholecalciferol Supplementation on Perioperative Vitamin D Status in Colorectal Surgery Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bio-Tech Pharmacal, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A growing body of evidence suggests that robust postoperative immune function is associated&#xD;
      with a lower risk of surgical site infections (SSIs). At the same time, vitamin D is&#xD;
      increasingly recognized as a key regulator of the innate and adaptive immune systems. The&#xD;
      investigators elected to conduct the current study in patients who will undergo colorectal&#xD;
      surgery since these patients are historically at higher risk of developing SSIs and therefore&#xD;
      would be ideal for future investigations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      While vitamin D insufficiency [25(OH)D &lt;30 ng/mL] is common in the general population,&#xD;
      hypovitaminosis D may affect 40-80% of patients in the perioperative setting. Recent evidence&#xD;
      also suggests that surgical stress may be associated with a 40% reduction in circulating&#xD;
      25(OH)D levels when compared to preoperative values. Moreover, the derangement in&#xD;
      perioperative 25(OH)D levels may be sustained for up to 3 months after surgery. This finding&#xD;
      has potential implications regarding modifiable risk factors for surgical site infections&#xD;
      (SSIs), which account for nearly 40% of all nosocomial infections. On aggregate, SSIs result&#xD;
      in 3.7 million extra hospital days per annum and an added burden of $1.6 billion in annual&#xD;
      healthcare costs. A growing body of evidence suggests that robust postoperative immune&#xD;
      function is associated with a lower risk of SSIs. At the same time, vitamin D is increasingly&#xD;
      recognized as a key regulator of the innate and adaptive immune systems. Yet, optimization of&#xD;
      perioperative vitamin D status remains grossly understudied. Although our overarching aim is&#xD;
      to study the impact of vitamin D status on SSIs, the focus of the current investigation is to&#xD;
      determine whether the administration of a &quot;bolus&quot; oral dose of cholecalciferol (vitamin D3)&#xD;
      in the preoperative setting alters vitamin D status in the perioperative setting (compared to&#xD;
      a placebo). The investigators elected to conduct the current study in patients who will&#xD;
      undergo colorectal surgery since these patients are historically at higher risk of developing&#xD;
      SSIs and therefore would be ideal for future investigations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent (%) Change in 25(OH)D 5 Days Following Supplementation With 100,000 IU Cholecalciferol</measure>
    <time_frame>Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days</time_frame>
    <description>3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent (%) Change in LL-37 5 Days Following Supplementation With 100,000 IU Cholecalciferol</measure>
    <time_frame>Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days</time_frame>
    <description>3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent (%) Change in Pre-surgical 25(OH)D Within 24 Hours of Surgery</measure>
    <time_frame>Patients will be followed between the day of surgery and 1 day after surgery</time_frame>
    <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent (%) Change in Pre-surgical LL-37 Within 24 Hours of Surgery</measure>
    <time_frame>Patients will be followed between the day of surgery and 1 day after surgery</time_frame>
    <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Percent (%) Change in Pre-surgical 25(OH)D 2 Weeks After Surgery</measure>
    <time_frame>Patients will be followed between the day of surgery and an average duration of 14 days after surgery</time_frame>
    <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37.</description>
  </other_outcome>
  <other_outcome>
    <measure>Percent (%) Change in Pre-surgical LL-37 2 Weeks After Surgery</measure>
    <time_frame>Patients will be followed between the day of surgery and an average duration of 14 days after surgery</time_frame>
    <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Hypovitaminosis D</condition>
  <arm_group>
    <arm_group_label>Cholecalciferol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A maximum of 40 patients will receive a one-time oral dose of 100,000 IU cholecalciferol 3-7 days before their scheduled elective surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A maximum of 40 patients will receive a one-time oral sugar pill 3-7 days before their scheduled elective surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>100,000 IU cholecalciferol</intervention_name>
    <description>active drug</description>
    <arm_group_label>Cholecalciferol</arm_group_label>
    <other_name>vitamin D3</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>comparator drug</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>sugar pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women;&#xD;
&#xD;
          -  18 years or older;&#xD;
&#xD;
          -  Scheduled for elective (non-emergent) colorectal surgery;&#xD;
&#xD;
          -  Cleared for anesthesia; and&#xD;
&#xD;
          -  Expected to stay overnight following surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Scheduled for a purely laparoscopic procedure;&#xD;
&#xD;
          -  Diagnosis of a terminal illness and/or in hospice care;&#xD;
&#xD;
          -  Inability to sign informed consent;&#xD;
&#xD;
          -  Inability to comply with study protocol;&#xD;
&#xD;
          -  Intending to start vitamin D supplementation within 30 days of surgery;&#xD;
&#xD;
          -  Intending to leave the Boston area during the follow-up period;&#xD;
&#xD;
          -  History of renal stones or hypercalcemia;&#xD;
&#xD;
          -  Medical conditions that can cause hypercalcemia (e.g. metastatic cancer, sarcoidosis,&#xD;
             myeloma primary hyperparathyroidism)&#xD;
&#xD;
          -  History of hypercalcemia&#xD;
&#xD;
          -  History of severe anemia (Hematocrit &lt;25%)&#xD;
&#xD;
          -  Medications that affect vitamin D metabolism (e.g. anti-epileptics, tuberculosis&#xD;
             medication); and&#xD;
&#xD;
          -  Already enrolled or planning to enroll in a research study that would conflict with&#xD;
             full participation in the current study or confound the observation or interpretation&#xD;
             of the study findings&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sadeq A Quraishi, MD, MHA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <results_first_submitted>March 28, 2017</results_first_submitted>
  <results_first_submitted_qc>August 29, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">September 28, 2017</results_first_posted>
  <last_update_submitted>August 29, 2017</last_update_submitted>
  <last_update_submitted_qc>August 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Sadeq A. Quraishi</investigator_full_name>
    <investigator_title>Assistant Professor of Anaesthesia, Harvard Medical School</investigator_title>
  </responsible_party>
  <keyword>vitamin D</keyword>
  <keyword>surgery</keyword>
  <keyword>acute stress</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rickets</mesh_term>
    <mesh_term>Avitaminosis</mesh_term>
    <mesh_term>Vitamin D Deficiency</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>Cholecalciferol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cholecalciferol</title>
          <description>40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery.&#xD;
100, 000 IU cholecalciferol</description>
        </group>
        <group group_id="P2">
          <title>Sugar Pill</title>
          <description>40 patients will receive a sugar pill orally 3-7 days before surgery.&#xD;
Placebo: sugar pill</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cholecalciferol</title>
          <description>40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery.&#xD;
100, 000 IU cholecalciferol</description>
        </group>
        <group group_id="B2">
          <title>Sugar Pill</title>
          <description>40 patients will receive a sugar pill orally 3-7 days before surgery.&#xD;
Placebo: sugar pill</description>
        </group>
        <group group_id="B3">
          <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="28"/>
            <count group_id="B2" value="32"/>
            <count group_id="B3" value="60"/>
          </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="56" spread="13"/>
                    <measurement group_id="B2" value="61" spread="13"/>
                    <measurement group_id="B3" value="57" spread="13"/>
                  </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="14"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent (%) Change in 25(OH)D 5 Days Following Supplementation With 100,000 IU Cholecalciferol</title>
        <description>3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37</description>
        <time_frame>Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days</time_frame>
        <population>Data are presented as percent change in levels between baseline assessment and day of surgery</population>
        <group_list>
          <group group_id="O1">
            <title>Cholecalciferol</title>
            <description>40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery.&#xD;
100, 000 IU cholecalciferol</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill</title>
            <description>40 patients will receive a sugar pill orally 3-7 days before surgery.&#xD;
Placebo: sugar pill</description>
          </group>
        </group_list>
        <measure>
          <title>Percent (%) Change in 25(OH)D 5 Days Following Supplementation With 100,000 IU Cholecalciferol</title>
          <description>3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37</description>
          <population>Data are presented as percent change in levels between baseline assessment and day of surgery</population>
          <units>percent change in 25(OH)D</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" spread="6"/>
                    <measurement group_id="O2" value="-2" spread="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent (%) Change in Pre-surgical 25(OH)D Within 24 Hours of Surgery</title>
        <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37.</description>
        <time_frame>Patients will be followed between the day of surgery and 1 day after surgery</time_frame>
        <population>Data are presented as percent change in levels between baseline assessment and day after surgery</population>
        <group_list>
          <group group_id="O1">
            <title>Cholecalciferol</title>
            <description>40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery.&#xD;
100, 000 IU cholecalciferol</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill</title>
            <description>40 patients will receive a sugar pill orally 3-7 days before surgery.&#xD;
Placebo: sugar pill</description>
          </group>
        </group_list>
        <measure>
          <title>Percent (%) Change in Pre-surgical 25(OH)D Within 24 Hours of Surgery</title>
          <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37.</description>
          <population>Data are presented as percent change in levels between baseline assessment and day after surgery</population>
          <units>Percent change in 25(OH)D</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5" spread="6"/>
                    <measurement group_id="O2" value="-4" spread="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percent (%) Change in Pre-surgical 25(OH)D 2 Weeks After Surgery</title>
        <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37.</description>
        <time_frame>Patients will be followed between the day of surgery and an average duration of 14 days after surgery</time_frame>
        <population>Data are presented as percent change in levels between baseline assessment and 2 weeks after surgery</population>
        <group_list>
          <group group_id="O1">
            <title>Cholecalciferol</title>
            <description>40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery.&#xD;
100, 000 IU cholecalciferol</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill</title>
            <description>40 patients will receive a sugar pill orally 3-7 days before surgery.&#xD;
Placebo: sugar pill</description>
          </group>
        </group_list>
        <measure>
          <title>Percent (%) Change in Pre-surgical 25(OH)D 2 Weeks After Surgery</title>
          <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37.</description>
          <population>Data are presented as percent change in levels between baseline assessment and 2 weeks after surgery</population>
          <units>Percent change in 25(OH)D</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" spread="7"/>
                    <measurement group_id="O2" value="1" spread="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percent (%) Change in LL-37 5 Days Following Supplementation With 100,000 IU Cholecalciferol</title>
        <description>3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37</description>
        <time_frame>Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days</time_frame>
        <population>Data are presented as percent change in levels between baseline assessment and day of surgery</population>
        <group_list>
          <group group_id="O1">
            <title>Cholecalciferol</title>
            <description>40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery.&#xD;
100, 000 IU cholecalciferol</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill</title>
            <description>40 patients will receive a sugar pill orally 3-7 days before surgery.&#xD;
Placebo: sugar pill</description>
          </group>
        </group_list>
        <measure>
          <title>Percent (%) Change in LL-37 5 Days Following Supplementation With 100,000 IU Cholecalciferol</title>
          <description>3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37</description>
          <population>Data are presented as percent change in levels between baseline assessment and day of surgery</population>
          <units>percent change in LL-37</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10" spread="17"/>
                    <measurement group_id="O2" value="-5" spread="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent (%) Change in Pre-surgical LL-37 Within 24 Hours of Surgery</title>
        <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37.</description>
        <time_frame>Patients will be followed between the day of surgery and 1 day after surgery</time_frame>
        <population>Data are presented as percent change in levels between baseline assessment and day after surgery</population>
        <group_list>
          <group group_id="O1">
            <title>Cholecalciferol</title>
            <description>40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery.&#xD;
100, 000 IU cholecalciferol</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill</title>
            <description>40 patients will receive a sugar pill orally 3-7 days before surgery.&#xD;
Placebo: sugar pill</description>
          </group>
        </group_list>
        <measure>
          <title>Percent (%) Change in Pre-surgical LL-37 Within 24 Hours of Surgery</title>
          <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37.</description>
          <population>Data are presented as percent change in levels between baseline assessment and day after surgery</population>
          <units>Percent change in LL-37</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3" spread="24"/>
                    <measurement group_id="O2" value="-5" spread="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percent (%) Change in Pre-surgical LL-37 2 Weeks After Surgery</title>
        <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37.</description>
        <time_frame>Patients will be followed between the day of surgery and an average duration of 14 days after surgery</time_frame>
        <population>Data are presented as percent change in levels between baseline assessment and 2 weeks after surgery</population>
        <group_list>
          <group group_id="O1">
            <title>Cholecalciferol</title>
            <description>40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery.&#xD;
100, 000 IU cholecalciferol</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill</title>
            <description>40 patients will receive a sugar pill orally 3-7 days before surgery.&#xD;
Placebo: sugar pill</description>
          </group>
        </group_list>
        <measure>
          <title>Percent (%) Change in Pre-surgical LL-37 2 Weeks After Surgery</title>
          <description>The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37.</description>
          <population>Data are presented as percent change in levels between baseline assessment and 2 weeks after surgery</population>
          <units>Percent change in LL-37</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16" spread="27"/>
                    <measurement group_id="O2" value="2" spread="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Data was collected over a period of 30 days post drug administration</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cholecalciferol</title>
          <description>40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery.&#xD;
100, 000 IU cholecalciferol</description>
        </group>
        <group group_id="E2">
          <title>Sugar Pill</title>
          <description>40 patients will receive a sugar pill orally 3-7 days before surgery.&#xD;
Placebo: sugar pill</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="32"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="32"/>
              </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>
    <limitations_and_caveats>A small sample size and a relatively homogenous patient cohort at a major teaching hospital limit the generalizability of results.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Sadeq A. Quraishi, MD</name_or_title>
      <organization>Massachusetts General Hospital</organization>
      <phone>617-726-3030</phone>
      <email>squraishi@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/NCT01689779
org study id: 2012P001852
nct id: NCT01689779
lead sponsor: 
collaborator: 
has dmc: Yes
A growing body of evidence suggests that robust postoperative immune function is associated
      with a lower risk of surgical site infections (SSIs). At the same time, vitamin D is
      increasingly recognized as a key regulator of the innate and adaptive immune systems. The
      investigators elected to conduct the current study in patients who will undergo colorectal
      surgery since these patients are historically at higher risk of developing SSIs and therefore
      would be ideal for future investigations.
While vitamin D insufficiency [25(OH)D <30 ng/mL] is common in the general population,
      hypovitaminosis D may affect 40-80% of patients in the perioperative setting. Recent evidence
      also suggests that surgical stress may be associated with a 40% reduction in circulating
      25(OH)D levels when compared to preoperative values. Moreover, the derangement in
      perioperative 25(OH)D levels may be sustained for up to 3 months after surgery. This finding
      has potential implications regarding modifiable risk factors for surgical site infections
      (SSIs), which account for nearly 40% of all nosocomial infections. On aggregate, SSIs result
      in 3.7 million extra hospital days per annum and an added burden of $1.6 billion in annual
      healthcare costs. A growing body of evidence suggests that robust postoperative immune
      function is associated with a lower risk of SSIs. At the same time, vitamin D is increasingly
      recognized as a key regulator of the innate and adaptive immune systems. Yet, optimization of
      perioperative vitamin D status remains grossly understudied. Although our overarching aim is
      to study the impact of vitamin D status on SSIs, the focus of the current investigation is to
      determine whether the administration of a "bolus" oral dose of cholecalciferol (vitamin D3)
      in the preoperative setting alters vitamin D status in the perioperative setting (compared to
      a placebo). The investigators elected to conduct the current study in patients who will
      undergo colorectal surgery since these patients are historically at higher risk of developing
      SSIs and therefore would be ideal for future investigations.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percent (%) Change in 25(OH)D 5 Days Following Supplementation With 100,000 IU Cholecalciferol
time frame: Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days
description: 3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37
measure: Percent (%) Change in LL-37 5 Days Following Supplementation With 100,000 IU Cholecalciferol
time frame: Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days
description: 3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37
measure: Percent (%) Change in Pre-surgical 25(OH)D Within 24 Hours of Surgery
time frame: Patients will be followed between the day of surgery and 1 day after surgery
description: The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37.
measure: Percent (%) Change in Pre-surgical LL-37 Within 24 Hours of Surgery
time frame: Patients will be followed between the day of surgery and 1 day after surgery
description: The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37.
measure: Percent (%) Change in Pre-surgical 25(OH)D 2 Weeks After Surgery
time frame: Patients will be followed between the day of surgery and an average duration of 14 days after surgery
description: The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37.
measure: Percent (%) Change in Pre-surgical LL-37 2 Weeks After Surgery
time frame: Patients will be followed between the day of surgery and an average duration of 14 days after surgery
description: The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37.
arm group label: Cholecalciferol
arm group type: Active Comparator
description: A maximum of 40 patients will receive a one-time oral dose of 100,000 IU cholecalciferol 3-7 days before their scheduled elective surgery.
arm group label: Placebo
arm group type: Placebo Comparator
description: A maximum of 40 patients will receive a one-time oral sugar pill 3-7 days before their scheduled elective surgery.
intervention type: Drug
intervention name: 100,000 IU cholecalciferol
description: active drug
arm group label: Cholecalciferol
other name: vitamin D3
intervention type: Drug
intervention name: Placebo
description: comparator drug
arm group label: Placebo
other name: sugar pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sadeq A Quraishi, MD, MHA
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Sadeq A. Quraishi
investigator title: Assistant Professor of Anaesthesia, Harvard Medical School
mesh term: Rickets
mesh term: Avitaminosis
mesh term: Vitamin D Deficiency
mesh term: Vitamin D
mesh term: Cholecalciferol
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: A small sample size and a relatively homogenous patient cohort at a major teaching hospital limit the generalizability of results.
point of contact: 