<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/NCT03306433</url>
  </required_header>
  <id_info>
    <org_study_id>17-0633</org_study_id>
    <nct_id>NCT03306433</nct_id>
  </id_info>
  <brief_title>Prevention of Enamel Demineralization by Use of K18-smooth Surface Sealant</brief_title>
  <acronym>K18</acronym>
  <official_title>Prevention of Enamel Demineralization in Fixed Appliance Orthodontic Patients Using UDMA-K18 Sealant to Prevent Microbial Attachment Compared to a UDMA Control and no Sealant, a Randomized Split Mouth Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Colorado School of Dental Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate effectiveness of a urethane dimethacrylate (UDMA)-quaternary&#xD;
      ammonium methacrylate (K18) resin (UDMA-K18) smooth surface sealant to prevent biofilm&#xD;
      attachment to tooth surfaces thereby eliminating the possibility for the tooth to be&#xD;
      demineralized. The hypothesis is that UDMA-K18 containing smooth surface sealant will be more&#xD;
      effective at reducing enamel demineralization than the UDMA control or no treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Esthetics is a motivating factor to seek orthodontic treatment. However, if oral hygiene is&#xD;
      inadequate during fixed appliance wear, unsightly white spot lesions (WSL) may develop. WSLs&#xD;
      are areas of enamel demineralization that develop due to microbial assault that manifest as&#xD;
      white, chalky opacity on the enamel. Urethane dimethacrylate (UDMA) can be modified to&#xD;
      produce an antimicrobial compound, UDMA-K18, that has been proven to decrease microbial&#xD;
      attachment in-vitro. (Sticker 2016) The use of a UDMA-K18 containing sealant may help to&#xD;
      eliminate the development of WSLs around orthodontic brackets.&#xD;
&#xD;
      This study will place experimental or control smooth surface resins on teeth that are&#xD;
      scheduled to be extracted for orthodontic reasons. These teeth are typically bicuspids that&#xD;
      are to be extracted to create room for the orthodontic movement of teeth. These teeth are&#xD;
      usually not extracted at the advent of first orthodontic bracket bonding but are extracted&#xD;
      about 30 days later. The design of this study is to place sealants on those teeth (or as&#xD;
      control, no sealant) and evaluate the teeth after they have been extracted.&#xD;
&#xD;
      Design: The study is a prospective, paired randomized control trial for which treatment (no&#xD;
      sealant, UDMA-control, or UDMA-K18 sealant) will be applied clinically and evaluated on&#xD;
      extracted teeth in laboratory conditions.&#xD;
&#xD;
      Procedures: Before bonding, one premolar per patient will be assigned to a group. The group&#xD;
      each premolar is assigned to will be determined by a randomized, computer generated program.&#xD;
      The allocation will be concealed in an opaque envelope that will be opened at the time of&#xD;
      initial bonding. If a fourth premolar is planned for extraction, a random selection of the&#xD;
      treatments will be selected in a 1:1:1 ratio and this treatment will be applied to the fourth&#xD;
      premolar.&#xD;
&#xD;
      At the time of initial bonding, the UDMA and UDMA-K18 sealant will be applied to the selected&#xD;
      premolar following manufacturer instructions. Briefly, the clinician will isolate the teeth&#xD;
      using the NOLA Dry Field System and excess saliva will be removed by drying the teeth with an&#xD;
      air-water syringe. In the treatment group, 37 % Phosphoric Acid will be applied to the entire&#xD;
      buccal surface for 30 seconds, rinsed, and dried. Next, the assigned sealant will be evenly&#xD;
      applied to the entire buccal surface of the premolar and light cured. The sealant which is&#xD;
      adhesive will be applied to the bracket pad and the bracket pad will be pushed to place,&#xD;
      excess cement will be removed and light cured.&#xD;
&#xD;
      In the control group, 37 % Phosphoric Acid will be applied for 30 seconds strictly to the&#xD;
      area where the bracket will be bonded on the buccal surface, rinsed, and dried. No sealant&#xD;
      will be applied. The adhesive sealant will be applied to the bracket pad and the bracket pad&#xD;
      will be pushed to place, excess cement will be removed and light cured. After 3-6 weeks, the&#xD;
      patient will have their premolars extracted. After extraction they will be placed in a Tooth&#xD;
      Storage Solution (25 % ethanol, 75 % water with the addition of saturated hydroxyapatite, 20&#xD;
      mg of NaN3, and 40 mg Thymol) that is antimicrobial and does not alter the tooth surface.&#xD;
      These teeth will be collected by the investigators for histologic study.&#xD;
&#xD;
      The collected, extracted teeth will be sectioned using a water-cooled, Buhler slow speed&#xD;
      diamond saw in three 2mm sections through the bracket base. A polarized light microscopy&#xD;
      (PLM) digitized photograph of the cross-sectional sample will be analyzed to determine the&#xD;
      depth of lesions, if present. The mineral density profile will be analyzed using contact&#xD;
      micro radiography (TMR).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 8, 2018</start_date>
  <completion_date type="Actual">December 7, 2018</completion_date>
  <primary_completion_date type="Actual">December 7, 2018</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>
    <intervention_model_description>prospective, paired randomized control trial for which treatment (no sealant, UDMA control, UDMA-K18 sealant) will be applied clinically and evaluated on extracted teeth in laboratory conditions.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The trial design is triple-blinded. The manufacturer will deliver the blinded treatments in identical bottles labelled A and B, therefore, neither the patient nor the clinician will know which treatment is rendered to each tooth. However, the no sealant control will not be blinded. Blinding will continue to be present during the histological portion of the experiment as the assessors will not be aware of which sealant was used to treat each tooth. After a blinded assessment, blinds will be lifted when between-group analysis is performed.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Mineral Density Determined by the Canary Caries Detection System</measure>
    <time_frame>Visit Window: 3-4 weeks.</time_frame>
    <description>The mineral density immediately below the surface of the tooth will lower if left unprotected to some extent.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>White Spot Lesion (WSL) Index</measure>
    <time_frame>Visit Window: 3-4 weeks.</time_frame>
    <description>The WSL Index is from 0 (no lesion) to 4 (severe lesion)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Dental Caries</condition>
  <arm_group>
    <arm_group_label>UDMA-K18</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>UDMA-K18 smooth surface sealant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>UDMA-control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>UDMA smooth surface sealant without K18</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Negative control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No intervention to provide baseline</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>UDMA-K18 smooth surface sealant</intervention_name>
    <description>The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.</description>
    <arm_group_label>UDMA-K18</arm_group_label>
    <arm_group_label>UDMA-control</arm_group_label>
    <other_name>UDMA-control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Orthodontic patients at the Department of Orthodontics Clinic, School of Dental&#xD;
             Medicine, University of Colorado who agree to consent to this study.&#xD;
&#xD;
          -  Orthodontic treatment plans that include fixed appliances from the second premolar to&#xD;
             second premolar in both arches.&#xD;
&#xD;
          -  Orthodontic treatment plans that include extractions of at least 3 bicuspids at about&#xD;
             1 month after bracket placement.&#xD;
&#xD;
          -  The patient has adequate oral hygiene&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of decalcification or restorations on any of the premolars planned for&#xD;
             extraction prior to orthodontic treatment,&#xD;
&#xD;
          -  Pregnant women (self reported)&#xD;
&#xD;
          -  Any condition that contraindicates orthodontic treatment,&#xD;
&#xD;
          -  Not willing to consent to the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clifton Carey, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor, Dir Translational Research, University of Colorado, School of Dental Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado, School of Dental Medicine</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Schmuck BD, Carey CM. Improved Contact X-Ray Microradiographic Method to Measure Mineral Density of Hard Dental Tissues. J Res Natl Inst Stand Technol. 2010 Apr 1;115(2):75-83. doi: 10.6028/jres.115.006. Print 2010 Mar-Apr.</citation>
    <PMID>21546983</PMID>
  </reference>
  <reference>
    <citation>Gong SQ, Niu LN, Kemp LK, Yiu CK, Ryou H, Qi YP, Blizzard JD, Nikonov S, Brackett MG, Messer RL, Wu CD, Mao J, Bryan Brister L, Rueggeberg FA, Arola DD, Pashley DH, Tay FR. Quaternary ammonium silane-functionalized, methacrylate resin composition with antimicrobial activities and self-repair potential. Acta Biomater. 2012 Sep;8(9):3270-82. doi: 10.1016/j.actbio.2012.05.031. Epub 2012 May 29.</citation>
    <PMID>22659173</PMID>
  </reference>
  <reference>
    <citation>Liu SY, Tonggu L, Niu LN, Gong SQ, Fan B, Wang L, Zhao JH, Huang C, Pashley DH, Tay FR. Antimicrobial activity of a quaternary ammonium methacryloxy silicate-containing acrylic resin: a randomised clinical trial. Sci Rep. 2016 Feb 23;6:21882. doi: 10.1038/srep21882.</citation>
    <PMID>26903314</PMID>
  </reference>
  <reference>
    <citation>Wefel JS, Harless JD. Comparison of artificial white spots by microradiography and polarized light microscopy. J Dent Res. 1984 Nov;63(11):1271-5. doi: 10.1177/00220345840630110301.</citation>
    <PMID>6094633</PMID>
  </reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>October 5, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <results_first_submitted>May 12, 2021</results_first_submitted>
  <results_first_submitted_qc>September 10, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">October 7, 2021</results_first_posted>
  <last_update_submitted>September 10, 2021</last_update_submitted>
  <last_update_submitted_qc>September 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>dental caries</keyword>
  <keyword>white spot lesion</keyword>
  <keyword>prevention</keyword>
  <keyword>smooth surface sealant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dental Caries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The COMIRB approval and the consent forms specify that we cannot share PHI except as mandated by law. Therefore we do not intend to share any IPD to other researchers.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 14, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT03306433/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment began in January 2018 and ended in October 2018. Participants were recruited from the patient pool at the University of Colorado School of Dental Medicine Department of Orthodontics. Eligible candidates were offered the opportunity to participate in the study.</recruitment_details>
      <pre_assignment_details>Participants were enrolled into the study if they met the inclusion criteria of having a planned orthodontic therapy that required extraction of at least 2 teeth and that those teeth were free of demineralization and did not have restorations.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Participants</title>
          <description>Participants were enrolled into the study if they met the inclusion criteria of having a planned orthodontic therapy that required extraction of at least 2 teeth and that those teeth were free of demineralization and did not have restorations. Enrolled participants were assigned to receive up to all three treatments. There were 16 participant total. Treatments included:&#xD;
UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.&#xD;
The adhesive used to bond the orthodontic bracket to the tooth UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>UDMA-K18</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Adhesive Control</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>UDMA-control</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient did not have teeth extracted</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Teeth not sent to the lab or participant only had two teeth for extraction</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>Participants were enrolled into the study if they met the inclusion criteria of having a planned orthodontic therapy that required extraction of at least 2 teeth and that those teeth were free of demineralization and did not have restorations. All 16 participants had all three treatments. Thus there were 16 participant total. Treatments included:&#xD;
UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.&#xD;
The adhesive used to bond the orthodontic bracket to the tooth UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Participant age was self reported. All groups had the same participants</description>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Age</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13.8" spread="2.3"/>
                  </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="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Canary Score</title>
          <description>The Canary Caries Detection System determines mineral quality (related to loss of mineral from the tooth). The measure is in Canary Numbers where 0 is no mineral loss and 100 is severe mineral loss.</description>
          <units>Canary Numbers</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7" lower_limit="0" upper_limit="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Mineral Density Determined by the Canary Caries Detection System</title>
        <description>The mineral density immediately below the surface of the tooth will lower if left unprotected to some extent.</description>
        <time_frame>Visit Window: 3-4 weeks.</time_frame>
        <population>In this split mouth (same mouth) design all participants receive all treatments.</population>
        <group_list>
          <group group_id="O1">
            <title>UDMA-K18</title>
            <description>UDMA-K18 smooth surface sealant&#xD;
UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.</description>
          </group>
          <group group_id="O2">
            <title>UDMA-control</title>
            <description>UDMA smooth surface sealant without K18&#xD;
UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.</description>
          </group>
          <group group_id="O3">
            <title>Adhesive Control</title>
            <description>The adhesive used to bond the orthodontic bracket to the tooth</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mineral Density Determined by the Canary Caries Detection System</title>
          <description>The mineral density immediately below the surface of the tooth will lower if left unprotected to some extent.</description>
          <population>In this split mouth (same mouth) design all participants receive all treatments.</population>
          <units>Canary Number</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.424" spread="3.288"/>
                    <measurement group_id="O2" value="31.125" spread="4.275"/>
                    <measurement group_id="O3" value="35.563" spread="7.378"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Paired difference test within each participant.</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The null hypothesis is that there are no significant paired differences between the groups. The power calculation is based on the observed variation and number of participants</non_inferiority_desc>
            <p_value>0.0003</p_value>
            <p_value_desc>Paired difference p value comparing UDMA-K18 vs Adhesive Control</p_value_desc>
            <method>Paired difference test, 2 sided</method>
            <param_type>Paired difference t-test</param_type>
            <param_value>-12.139</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>7.101</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>There are 12 participants (pairs) for this comparison</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Paired comparison</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Null hypothesis was that there were no differences between the groups</non_inferiority_desc>
            <p_value>0.0063</p_value>
            <p_value_desc>Paired differrnce between UDMA-K18 and UDMA control</p_value_desc>
            <method>Paired difference test, 2 sided</method>
            <param_type>Paired difference t-test</param_type>
            <param_value>-7.412</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>6.049</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>There are 9 participant pairs for this comparison</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>White Spot Lesion (WSL) Index</title>
        <description>The WSL Index is from 0 (no lesion) to 4 (severe lesion)</description>
        <time_frame>Visit Window: 3-4 weeks.</time_frame>
        <population>Split mouth design : All participants received all treatments</population>
        <group_list>
          <group group_id="O1">
            <title>UDMA-K18</title>
            <description>UDMA-K18 smooth surface sealant&#xD;
UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.</description>
          </group>
          <group group_id="O2">
            <title>UDMA-control</title>
            <description>UDMA smooth surface sealant without K18&#xD;
UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.</description>
          </group>
          <group group_id="O3">
            <title>Adhesive Control</title>
            <description>The adhesive used to bond the orthodontic bracket to the tooth</description>
          </group>
        </group_list>
        <measure>
          <title>White Spot Lesion (WSL) Index</title>
          <description>The WSL Index is from 0 (no lesion) to 4 (severe lesion)</description>
          <population>Split mouth design : All participants received all treatments</population>
          <units>White spot Index</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="2"/>
                    <measurement group_id="O2" value="2" lower_limit="0" upper_limit="2"/>
                    <measurement group_id="O3" value="2" lower_limit="1" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>WSL Index is non-parametric</groups_desc>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The Null hypothesis was that there would be no differences between the groups</non_inferiority_desc>
            <p_value>0.0033</p_value>
            <method>Chi-squared</method>
            <param_type>Chi Square on WSL Index frequency</param_type>
            <param_value>15.77</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>The null hypothesis was that there would not be any differences between the groups</non_inferiority_desc>
            <p_value>0.1450</p_value>
            <method>Chi-squared</method>
            <param_type>Chi Square on WSL Index frequency</param_type>
            <param_value>6.8321</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>10 Months, January 2018 to October 2018</time_frame>
      <desc>Study participants were provided with a 24-hour hot line to call if they experienced any discomfort associated with the placement of the sealant or orthodontic bracket.</desc>
      <group_list>
        <group group_id="E1">
          <title>UDMA-K18</title>
          <description>UDMA-K18 smooth surface sealant&#xD;
UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.</description>
        </group>
        <group group_id="E2">
          <title>UDMA-control</title>
          <description>UDMA smooth surface sealant without K18&#xD;
UDMA-K18 smooth surface sealant: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.</description>
        </group>
        <group group_id="E3">
          <title>Adhesive Control</title>
          <description>The adhesive used to bond the orthodontic bracket to the tooth</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="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
              </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="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Clifton Carey</name_or_title>
      <organization>University of Colorado, SoDM</organization>
      <phone>3037241046</phone>
      <email>clifton.carey@cuanschutz.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/NCT03306433
org study id: 17-0633
nct id: NCT03306433
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
This study will evaluate effectiveness of a urethane dimethacrylate (UDMA)-quaternary
      ammonium methacrylate (K18) resin (UDMA-K18) smooth surface sealant to prevent biofilm
      attachment to tooth surfaces thereby eliminating the possibility for the tooth to be
      demineralized. The hypothesis is that UDMA-K18 containing smooth surface sealant will be more
      effective at reducing enamel demineralization than the UDMA control or no treatment.
Esthetics is a motivating factor to seek orthodontic treatment. However, if oral hygiene is
      inadequate during fixed appliance wear, unsightly white spot lesions (WSL) may develop. WSLs
      are areas of enamel demineralization that develop due to microbial assault that manifest as
      white, chalky opacity on the enamel. Urethane dimethacrylate (UDMA) can be modified to
      produce an antimicrobial compound, UDMA-K18, that has been proven to decrease microbial
      attachment in-vitro. (Sticker 2016) The use of a UDMA-K18 containing sealant may help to
      eliminate the development of WSLs around orthodontic brackets.

      This study will place experimental or control smooth surface resins on teeth that are
      scheduled to be extracted for orthodontic reasons. These teeth are typically bicuspids that
      are to be extracted to create room for the orthodontic movement of teeth. These teeth are
      usually not extracted at the advent of first orthodontic bracket bonding but are extracted
      about 30 days later. The design of this study is to place sealants on those teeth (or as
      control, no sealant) and evaluate the teeth after they have been extracted.

      Design: The study is a prospective, paired randomized control trial for which treatment (no
      sealant, UDMA-control, or UDMA-K18 sealant) will be applied clinically and evaluated on
      extracted teeth in laboratory conditions.

      Procedures: Before bonding, one premolar per patient will be assigned to a group. The group
      each premolar is assigned to will be determined by a randomized, computer generated program.
      The allocation will be concealed in an opaque envelope that will be opened at the time of
      initial bonding. If a fourth premolar is planned for extraction, a random selection of the
      treatments will be selected in a 1:1:1 ratio and this treatment will be applied to the fourth
      premolar.

      At the time of initial bonding, the UDMA and UDMA-K18 sealant will be applied to the selected
      premolar following manufacturer instructions. Briefly, the clinician will isolate the teeth
      using the NOLA Dry Field System and excess saliva will be removed by drying the teeth with an
      air-water syringe. In the treatment group, 37 % Phosphoric Acid will be applied to the entire
      buccal surface for 30 seconds, rinsed, and dried. Next, the assigned sealant will be evenly
      applied to the entire buccal surface of the premolar and light cured. The sealant which is
      adhesive will be applied to the bracket pad and the bracket pad will be pushed to place,
      excess cement will be removed and light cured.

      In the control group, 37 % Phosphoric Acid will be applied for 30 seconds strictly to the
      area where the bracket will be bonded on the buccal surface, rinsed, and dried. No sealant
      will be applied. The adhesive sealant will be applied to the bracket pad and the bracket pad
      will be pushed to place, excess cement will be removed and light cured. After 3-6 weeks, the
      patient will have their premolars extracted. After extraction they will be placed in a Tooth
      Storage Solution (25 % ethanol, 75 % water with the addition of saturated hydroxyapatite, 20
      mg of NaN3, and 40 mg Thymol) that is antimicrobial and does not alter the tooth surface.
      These teeth will be collected by the investigators for histologic study.

      The collected, extracted teeth will be sectioned using a water-cooled, Buhler slow speed
      diamond saw in three 2mm sections through the bracket base. A polarized light microscopy
      (PLM) digitized photograph of the cross-sectional sample will be analyzed to determine the
      depth of lesions, if present. The mineral density profile will be analyzed using contact
      micro radiography (TMR).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: prospective, paired randomized control trial for which treatment (no sealant, UDMA control, UDMA-K18 sealant) will be applied clinically and evaluated on extracted teeth in laboratory conditions.
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The trial design is triple-blinded. The manufacturer will deliver the blinded treatments in identical bottles labelled A and B, therefore, neither the patient nor the clinician will know which treatment is rendered to each tooth. However, the no sealant control will not be blinded. Blinding will continue to be present during the histological portion of the experiment as the assessors will not be aware of which sealant was used to treat each tooth. After a blinded assessment, blinds will be lifted when between-group analysis is performed.
measure: Change in Mineral Density Determined by the Canary Caries Detection System
time frame: Visit Window: 3-4 weeks.
description: The mineral density immediately below the surface of the tooth will lower if left unprotected to some extent.
measure: White Spot Lesion (WSL) Index
time frame: Visit Window: 3-4 weeks.
description: The WSL Index is from 0 (no lesion) to 4 (severe lesion)
arm group label: UDMA-K18
arm group type: Experimental
description: UDMA-K18 smooth surface sealant
arm group label: UDMA-control
arm group type: Placebo Comparator
description: UDMA smooth surface sealant without K18
arm group label: Negative control
arm group type: No Intervention
description: No intervention to provide baseline
intervention type: Device
intervention name: UDMA-K18 smooth surface sealant
description: The K18 as part of the UDMA polymer network (UDMA-K18) is hypothesized to prevent microbial attachment to the surface.
arm group label: UDMA-K18
arm group label: UDMA-control
other name: UDMA-control
criteria: 
gender: All
minimum age: 12 Years
maximum age: 89 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clifton Carey, PhD
role: Principal Investigator
affiliation: Professor, Dir Translational Research, University of Colorado, School of Dental Medicine
facility: 
country: United States
citation: Schmuck BD, Carey CM. Improved Contact X-Ray Microradiographic Method to Measure Mineral Density of Hard Dental Tissues. J Res Natl Inst Stand Technol. 2010 Apr 1;115(2):75-83. doi: 10.6028/jres.115.006. Print 2010 Mar-Apr.
PMID: 21546983
citation: Gong SQ, Niu LN, Kemp LK, Yiu CK, Ryou H, Qi YP, Blizzard JD, Nikonov S, Brackett MG, Messer RL, Wu CD, Mao J, Bryan Brister L, Rueggeberg FA, Arola DD, Pashley DH, Tay FR. Quaternary ammonium silane-functionalized, methacrylate resin composition with antimicrobial activities and self-repair potential. Acta Biomater. 2012 Sep;8(9):3270-82. doi: 10.1016/j.actbio.2012.05.031. Epub 2012 May 29.
PMID: 22659173
citation: Liu SY, Tonggu L, Niu LN, Gong SQ, Fan B, Wang L, Zhao JH, Huang C, Pashley DH, Tay FR. Antimicrobial activity of a quaternary ammonium methacryloxy silicate-containing acrylic resin: a randomised clinical trial. Sci Rep. 2016 Feb 23;6:21882. doi: 10.1038/srep21882.
PMID: 26903314
citation: Wefel JS, Harless JD. Comparison of artificial white spots by microradiography and polarized light microscopy. J Dent Res. 1984 Nov;63(11):1271-5. doi: 10.1177/00220345840630110301.
PMID: 6094633
responsible party type: Sponsor
mesh term: Dental Caries
sharing ipd: No
ipd description: The COMIRB approval and the consent forms specify that we cannot share PHI except as mandated by law. Therefore we do not intend to share any IPD to other researchers.
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 