<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/NCT01691833</url>
  </required_header>
  <id_info>
    <org_study_id>01-11-09A</org_study_id>
    <nct_id>NCT01691833</nct_id>
  </id_info>
  <brief_title>The Effect of Hypovitaminosis D and Vitamin D Supplementation on Fracture Nonunion Rates</brief_title>
  <acronym>VitD</acronym>
  <official_title>The Effect of Hypovitaminosis D and Vitamin D Supplementation on Fracture Nonunion Rates</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to determine whether vitamin D supplementation in patients with&#xD;
      hypovitaminosis D can decrease nonunion (failure to heal) incidence in patients with&#xD;
      fractures of the humerus, femur, or tibia. The central hypothesis of the study is that&#xD;
      vitamin D supplementation in patients with fractures and hypovitaminosis D will decrease the&#xD;
      risk of nonunion compared to placebo treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vitamin D plays an important role in maintaining calcium and phosphate balance in the body&#xD;
      and is important for maintenance of bone formation, remodeling, and healing. An extensive&#xD;
      literature search indicates that although there is evidence that vitamin D deficiency is&#xD;
      associated with fracture risk, there is no evidence of the role of vitamin D deficiency in&#xD;
      subsequent failure to heal. The aims of study were to: 1) quantify the rate of&#xD;
      hypovitaminosis D in an orthopedic trauma population in the Southeastern United States; 2)&#xD;
      determine the rate of nonunion in vitamin D deficient patients, and 3) assess the feasibility&#xD;
      of acute high-dose vitamin-D supplementation in hypovitaminosis D patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2011</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</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>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fracture Union</measure>
    <time_frame>up to 9 months post-surgery</time_frame>
    <description>Fracture Union is define as either clinical or radiological union. Clinical union defined as the absence of pain at the fracture site with the ability to bear full weight on the extremity without pain for activities of daily living (ambulation, lifting, carrying). Radiological union was determined by two blinded, independent review-ers and defined as the presence of bridging callus across at least three of four cortices or two of four cortices with a stable implant. When discrepancies between clinical and radiological union arose, the clinical assessment of union was preferred. Discrepancies in radiological outcomes were re-examined and a consensus view was obtained between reviewers if needed, to determine the outcome.If a patient did not meet the criteria for union and had at least nine months of follow•up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fracture Non-union</measure>
    <time_frame>9 months</time_frame>
    <description>If a patient did not meet the criteria for union and had at least nine months of follow-up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fixation Failure</measure>
    <time_frame>three months</time_frame>
    <description>Early failure of fixation was defined as the need to revise the fixation within three months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Deep Infection</measure>
    <time_frame>15 months</time_frame>
    <description>A deep infection was defined as an unexpected return to theatre for irrigation and debridement with positive cultures from below the fascia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lost to Follow-up</measure>
    <time_frame>15 months</time_frame>
    <description>Lost to follow-up if they did not meet the criteria for an outcome by 15 months after injury or surgery; were without another scheduled follow-up appointment, could not be contacted or refused to return for evaluation or send alternate records when contacted.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">113</enrollment>
  <condition>Hypovitaminosis D</condition>
  <arm_group>
    <arm_group_label>Vitamin D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normovitaminosis</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients with normovitaminosis( levels greater than or equal to 30ng/ml) will receive no intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D</intervention_name>
    <description>Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.</description>
    <arm_group_label>Vitamin D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Patients that are Vitamin D deficient maybe randomized to the placebo group D.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  presence of a long bone fracture (humerus, femur, or tibia)&#xD;
&#xD;
          -  age greater than or equal to 18 years&#xD;
&#xD;
          -  ability to follow-up at our clinic for 12 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pathologic fractures (i.e. occuring in the presence of abnormal bone such as a tumor,&#xD;
             cyst, or Paget's disease)&#xD;
&#xD;
          -  open fractures (i.e. associated skin disruption) of Gustilo-Anderson type IIIB or C&#xD;
             (i.e. significant soft-tissue and bone devitalization)&#xD;
&#xD;
          -  presence of multiple fractures&#xD;
&#xD;
          -  delay in presentation for initial treatment of more than 2 weeks from the time of&#xD;
             injury&#xD;
&#xD;
          -  preexisting disorders known to adversely affect bone healing (e.g. diabetes mellitus&#xD;
             with HbA1C greater than or equal to 7, peripheral vascular disease, certain connective&#xD;
             tissue disorders, and congenital or acquired disorders of bone metabolism)&#xD;
&#xD;
          -  preexisting disorders affecting Vitamin D metabolism and/or calcium phosphate&#xD;
             homeostasis (e.g. renal failure, hepatic failure, congenital defects in vitamin D&#xD;
             metabolism, parathyroid disorders, conditions causing abnormal calcium and/or&#xD;
             phosphate absorption)&#xD;
&#xD;
          -  pregnant patients&#xD;
&#xD;
          -  patients who are unable to provide consent for the study&#xD;
&#xD;
          -  patients who are unable to swallow due to acuity of illness or physiologic reason&#xD;
&#xD;
          -  prisoners who are patients because of their vulnerable population and inability to&#xD;
             follow-up&#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>Madhav Karunakar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rachel Seymour, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Christine Churchill, MA</last_name>
    <role>Study Chair</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Carolinas Medical Center</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <results_first_submitted>February 2, 2018</results_first_submitted>
  <results_first_submitted_qc>October 3, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">February 15, 2019</results_first_posted>
  <last_update_submitted>July 12, 2022</last_update_submitted>
  <last_update_submitted_qc>July 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vitamin D</keyword>
  <keyword>nonunion</keyword>
  <keyword>long bone fracture</keyword>
  <keyword>hypovitaminosis D</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>
    <mesh_term>Fractures, Ununited</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Hypovitaminosis- Vitamin D Group</title>
          <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Vitamin D: Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.</description>
        </group>
        <group group_id="P2">
          <title>Hypovitaminosis- Placebo Group</title>
          <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Placebo: Patients that are Vitamin D deficient maybe randomized to the placebo group D.</description>
        </group>
        <group group_id="P3">
          <title>Normovitaminosis</title>
          <description>Patients with normovitaminosis D (levels greater than or equal to 30ng/ml) did not participate in the randomized portion of the study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="50"/>
                <participants group_id="P3" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="49"/>
                <participants group_id="P2" count="49"/>
                <participants group_id="P3" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vitamin D</title>
          <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Vitamin D: Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Placebo: Patients that are Vitamin D deficient maybe randomized to the placebo group D.</description>
        </group>
        <group group_id="B3">
          <title>Normovitaminosis</title>
          <description>Patients with normovitaminosis D (levels greater than or equal to 30ng/ml) did not participate in the randomized portion of the study.</description>
        </group>
        <group group_id="B4">
          <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="50"/>
            <count group_id="B2" value="50"/>
            <count group_id="B3" value="13"/>
            <count group_id="B4" value="113"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.9" spread="13.1"/>
                    <measurement group_id="B2" value="35.5" spread="12.1"/>
                    <measurement group_id="B3" value="39.9" spread="11.7"/>
                    <measurement group_id="B4" value="37.4" spread="12.6"/>
                  </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="16"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Injury Type</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Humerus</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Femur</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="55"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Tibia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tobacco use ( current)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.4" spread="6.3"/>
                    <measurement group_id="B2" value="27.8" spread="6.5"/>
                    <measurement group_id="B3" value="25.5" spread="4.87"/>
                    <measurement group_id="B4" value="28.3" spread="6.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Operatively treated</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior use of Vitamins</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diabetes mellitus</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Fracture Union</title>
        <description>Fracture Union is define as either clinical or radiological union. Clinical union defined as the absence of pain at the fracture site with the ability to bear full weight on the extremity without pain for activities of daily living (ambulation, lifting, carrying). Radiological union was determined by two blinded, independent review-ers and defined as the presence of bridging callus across at least three of four cortices or two of four cortices with a stable implant. When discrepancies between clinical and radiological union arose, the clinical assessment of union was preferred. Discrepancies in radiological outcomes were re-examined and a consensus view was obtained between reviewers if needed, to determine the outcome.If a patient did not meet the criteria for union and had at least nine months of follow•up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion.</description>
        <time_frame>up to 9 months post-surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Hypovitaminosis- Vitamin D Group</title>
            <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Vitamin D: Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.</description>
          </group>
          <group group_id="O2">
            <title>Hypovitaminosis- Placebo Group</title>
            <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Placebo: Patients that are Vitamin D deficient maybe randomized to the placebo group D.</description>
          </group>
          <group group_id="O3">
            <title>Normovitaminosis</title>
            <description>Patients with normovitaminosis D (levels greater than or equal to 30ng/ml) did not participate in the randomized portion of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Fracture Union</title>
          <description>Fracture Union is define as either clinical or radiological union. Clinical union defined as the absence of pain at the fracture site with the ability to bear full weight on the extremity without pain for activities of daily living (ambulation, lifting, carrying). Radiological union was determined by two blinded, independent review-ers and defined as the presence of bridging callus across at least three of four cortices or two of four cortices with a stable implant. When discrepancies between clinical and radiological union arose, the clinical assessment of union was preferred. Discrepancies in radiological outcomes were re-examined and a consensus view was obtained between reviewers if needed, to determine the outcome.If a patient did not meet the criteria for union and had at least nine months of follow•up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                    <measurement group_id="O2" value="39"/>
                    <measurement group_id="O3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Fracture Non-union</title>
        <description>If a patient did not meet the criteria for union and had at least nine months of follow-up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion.</description>
        <time_frame>9 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Hypovitaminosis- Vitamin D Group</title>
            <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Vitamin D: Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.</description>
          </group>
          <group group_id="O2">
            <title>Hypovitaminosis- Placebo Group</title>
            <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Placebo: Patients that are Vitamin D deficient maybe randomized to the placebo group D.</description>
          </group>
          <group group_id="O3">
            <title>Normovitaminosis</title>
            <description>Patients with normovitaminosis D (levels greater than or equal to 30ng/ml) did not participate in the randomized portion of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Fracture Non-union</title>
          <description>If a patient did not meet the criteria for union and had at least nine months of follow-up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fixation Failure</title>
        <description>Early failure of fixation was defined as the need to revise the fixation within three months.</description>
        <time_frame>three months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Hypovitaminosis- Vitamin D Group</title>
            <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Vitamin D: Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.</description>
          </group>
          <group group_id="O2">
            <title>Hypovitaminosis- Placebo Group</title>
            <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Placebo: Patients that are Vitamin D deficient maybe randomized to the placebo group D.</description>
          </group>
          <group group_id="O3">
            <title>Normovitaminosis</title>
            <description>Patients with normovitaminosis D (levels greater than or equal to 30ng/ml) did not participate in the randomized portion of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Fixation Failure</title>
          <description>Early failure of fixation was defined as the need to revise the fixation within three months.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Deep Infection</title>
        <description>A deep infection was defined as an unexpected return to theatre for irrigation and debridement with positive cultures from below the fascia.</description>
        <time_frame>15 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Hypovitaminosis- Vitamin D Group</title>
            <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Vitamin D: Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.</description>
          </group>
          <group group_id="O2">
            <title>Hypovitaminosis- Placebo Group</title>
            <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Placebo: Patients that are Vitamin D deficient maybe randomized to the placebo group D.</description>
          </group>
          <group group_id="O3">
            <title>Normovitaminosis</title>
            <description>Patients with normovitaminosis D (levels greater than or equal to 30ng/ml) did not participate in the randomized portion of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Deep Infection</title>
          <description>A deep infection was defined as an unexpected return to theatre for irrigation and debridement with positive cultures from below the fascia.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lost to Follow-up</title>
        <description>Lost to follow-up if they did not meet the criteria for an outcome by 15 months after injury or surgery; were without another scheduled follow-up appointment, could not be contacted or refused to return for evaluation or send alternate records when contacted.</description>
        <time_frame>15 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Hypovitaminosis- Vitamin D Group</title>
            <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Vitamin D: Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.</description>
          </group>
          <group group_id="O2">
            <title>Hypovitaminosis- Placebo Group</title>
            <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Placebo: Patients that are Vitamin D deficient maybe randomized to the placebo group D.</description>
          </group>
          <group group_id="O3">
            <title>Normovitaminosis</title>
            <description>Patients with normovitaminosis D (levels greater than or equal to 30ng/ml) did not participate in the randomized portion of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Lost to Follow-up</title>
          <description>Lost to follow-up if they did not meet the criteria for an outcome by 15 months after injury or surgery; were without another scheduled follow-up appointment, could not be contacted or refused to return for evaluation or send alternate records when contacted.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="7"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>15 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Hypovitaminosis- Vitamin D Group</title>
          <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Vitamin D: Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.</description>
        </group>
        <group group_id="E2">
          <title>Hypovitaminosis- Placebo Group</title>
          <description>Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.&#xD;
Placebo: Patients that are Vitamin D deficient maybe randomized to the placebo group D.</description>
        </group>
        <group group_id="E3">
          <title>Normovitaminosis</title>
          <description>Patients with normovitaminosis D (levels greater than or equal to 30ng/ml) did not participate in the randomized portion of the study.</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="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="13"/>
              </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="50"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="50"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Rachel Seymour</name_or_title>
      <organization>Carolinas Healthcare System</organization>
      <phone>704-355-2000</phone>
      <email>Rachel.Seymour@carolinas.org</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/NCT01691833
org study id: 01-11-09A
nct id: NCT01691833
lead sponsor: 
has dmc: Yes
The purpose of the study is to determine whether vitamin D supplementation in patients with
      hypovitaminosis D can decrease nonunion (failure to heal) incidence in patients with
      fractures of the humerus, femur, or tibia. The central hypothesis of the study is that
      vitamin D supplementation in patients with fractures and hypovitaminosis D will decrease the
      risk of nonunion compared to placebo treatment.
Vitamin D plays an important role in maintaining calcium and phosphate balance in the body
      and is important for maintenance of bone formation, remodeling, and healing. An extensive
      literature search indicates that although there is evidence that vitamin D deficiency is
      associated with fracture risk, there is no evidence of the role of vitamin D deficiency in
      subsequent failure to heal. The aims of study were to: 1) quantify the rate of
      hypovitaminosis D in an orthopedic trauma population in the Southeastern United States; 2)
      determine the rate of nonunion in vitamin D deficient patients, and 3) assess the feasibility
      of acute high-dose vitamin-D supplementation in hypovitaminosis D patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Fracture Union
time frame: up to 9 months post-surgery
description: Fracture Union is define as either clinical or radiological union. Clinical union defined as the absence of pain at the fracture site with the ability to bear full weight on the extremity without pain for activities of daily living (ambulation, lifting, carrying). Radiological union was determined by two blinded, independent review-ers and defined as the presence of bridging callus across at least three of four cortices or two of four cortices with a stable implant. When discrepancies between clinical and radiological union arose, the clinical assessment of union was preferred. Discrepancies in radiological outcomes were re-examined and a consensus view was obtained between reviewers if needed, to determine the outcome.If a patient did not meet the criteria for union and had at least nine months of follow•up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion.
measure: Fracture Non-union
time frame: 9 months
description: If a patient did not meet the criteria for union and had at least nine months of follow-up or underwent re-operation for a diagnosis of a nonunion, they were deemed to have a nonunion.
measure: Fixation Failure
time frame: three months
description: Early failure of fixation was defined as the need to revise the fixation within three months.
measure: Deep Infection
time frame: 15 months
description: A deep infection was defined as an unexpected return to theatre for irrigation and debridement with positive cultures from below the fascia.
measure: Lost to Follow-up
time frame: 15 months
description: Lost to follow-up if they did not meet the criteria for an outcome by 15 months after injury or surgery; were without another scheduled follow-up appointment, could not be contacted or refused to return for evaluation or send alternate records when contacted.
arm group label: Vitamin D
arm group type: Experimental
description: Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients that are deficient in Vitamin D will be assigned to the randomized arm of the study. They will be randomly chosen to receive either the Vitamin D supplement or the placebo.
arm group label: Normovitaminosis
arm group type: No Intervention
description: Patients with normovitaminosis( levels greater than or equal to 30ng/ml) will receive no intervention.
intervention type: Dietary Supplement
intervention name: Vitamin D
description: Patients that are Vitamin D deficient and randomized to the treatment group will receive a 10,000 IU dose of Vitamin D.
arm group label: Vitamin D
intervention type: Dietary Supplement
intervention name: Placebo
description: Patients that are Vitamin D deficient maybe randomized to the placebo group D.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Madhav Karunakar, MD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
last name: Rachel Seymour, PhD
role: Study Director
affiliation: Wake Forest University Health Sciences
last name: Christine Churchill, MA
role: Study Chair
affiliation: Wake Forest University Health Sciences
facility: 
country: United States
responsible party type: Sponsor
mesh term: Rickets
mesh term: Avitaminosis
mesh term: Vitamin D Deficiency
mesh term: Fractures, Ununited
mesh term: Vitamin D
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 