<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/NCT03031899</url>
  </required_header>
  <id_info>
    <org_study_id>219/2014-15</org_study_id>
    <nct_id>NCT03031899</nct_id>
  </id_info>
  <brief_title>Comparison or Rose Bengal and Toluidine Blue Staining for Lesion Detection Efficacy</brief_title>
  <official_title>Efficacy of Rose Bengal in Comparison With Toluidine Blue in Detection of Premalignant Lesions: a Preliminary Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Oxford Dental College, Hospital and Research Center, Bangalore, India</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Oxford Dental College, Hospital and Research Center, Bangalore, India</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Abstract&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To study the diagnostic efficiency of Rose Bengal with Toluidine blue in detecting the biopsy&#xD;
      sites and thus establish an accurate diagnosis in oral premalignant lesions.&#xD;
&#xD;
      Materials and method:&#xD;
&#xD;
      In our study 27 patients with 41 lesions were included. Since one patient had not quit the&#xD;
      habit in the two weeks following initial examination and another lesion disappeared in the&#xD;
      waiting period, 2 patients (3 lesions) were not included in the study. Out of 38 lesions&#xD;
      diagnosed based on clinical criteria, 32 were leukoplakia, 5 lichen planus and 1 SCC. After&#xD;
      initial examination they were subjected to Rose Bengal and Toluidine blue stain. If stained&#xD;
      positive they were subjected to biopsy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction Toluidine blue staining is the most common technique used for the early&#xD;
      detection of dysplastic changes in patients with premalignant lesions. One meta-analysis of&#xD;
      Rosenberg et al. previously published reported sensitivity ranged from 93.5% to 97.8% and the&#xD;
      specificity ranged from 73.3% to 92.9%. Zang et al reported that TB not only detects&#xD;
      high-grade dysplasia but detects OPLs with minimal or no dysplasia with high-risk clinical&#xD;
      and molecular attributes.4 But, studies have shown as high as 30% risk of false-positive&#xD;
      staining.&#xD;
&#xD;
      Rose Bengal (RB) has been widely used to diagnose various ocular surface disorders including&#xD;
      delineation of the extent of corneal and conjunctival neoplasms. It has been believed to&#xD;
      stain desquamated ocular epithelial cells, dead or degenerated cells, or wherever there is&#xD;
      poor protection of the surface epithelium by the preocular tear ﬁlm rather than lack of cell&#xD;
      vitality. These characteristic features of RB lead the researchers to apply it in oral&#xD;
      premalignant lesions.5 In none of the studies, reliability of RB stains was not compared with&#xD;
      existing or previously practiced methods in oral premalignant lesions. Hence this study was&#xD;
      undertaken with the aim of comparing the RB and TB stain and for early detection of dysplasia&#xD;
      in oral premalignant lesions.&#xD;
&#xD;
      Materials and Methods:&#xD;
&#xD;
      Study group consists of 41 oral premalignant lesions in patients visiting the Department of&#xD;
      Oral Medicine and Radiology of The oxford dental college and hospital, Bangalore. Patients&#xD;
      with OSMF, patients with bleeding disorders, patient with other systemic diseases were&#xD;
      excluded from the study.To perform the present study, ethical clearance was obtained from the&#xD;
      Institutional Ethical Board. Study procedure was explained and informed consent was taken&#xD;
      from the selected patients with premalignant lesions. The patients with lesions were&#xD;
      subjected to detailed case history, intra oral examination and photographs of the lesions&#xD;
      were recorded. Patients with habits were counselled to quit the habit and recalled after 2&#xD;
      weeks for staining. Since one patient had not quit the habit in the two weeks from first&#xD;
      visit, in another patient the lesion disappeared in two weeks 2 patients (3 lesions) were not&#xD;
      included in the study. (Graph1)&#xD;
&#xD;
      Initially patients were asked to rinse their mouth with distilled water for 1 minute. 1% RB&#xD;
      solution was applied with a cotton tip for 2 minutes. Again patients were asked to rinse&#xD;
      their mouth for 1 minute with distilled water to remove excess RB solution and the area which&#xD;
      had taken up the stain was photographed. Following this, patients were asked to rinse their&#xD;
      mouth with 1% acetic acid for 1 min to remove the remaining RB stain from the lesion and were&#xD;
      prepared for TB staining. 1%Toluidineblue is applied over the lesion and after 30 seconds&#xD;
      patients were made to swish with 1% acetic acid and the area stained was recorded&#xD;
      photographically.&#xD;
&#xD;
      These two photographs were assessed and if the stained area was similar in both the&#xD;
      procedures single biopsy was taken. If the stained areas were different two different&#xD;
      biopsies were taken.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2015</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number and Percentage of Lesions That Were Stained Positive</measure>
    <time_frame>2 weeks</time_frame>
    <description>outcome measure1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sensitivity and Specificity (Percentage of True Positives and True Negatives)</measure>
    <time_frame>2 weeks</time_frame>
    <description>sensitivity: Percentage of lesions stained positive with Toluidine blue stain that were also stained positive with Rose Bengal stain specificity: Percentage of lesions stained negative with Toluidine blue stain that were also stained negative with Rose Bengal stain</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Presence of Dysplasia in Biopsied Lesions That Were Stained by Rose Bengal</measure>
    <time_frame>2 weeks</time_frame>
    <description>this outcome measure was limited to the biopsied lesions.additionally, the intent of this outcome measure was only to study early detection of dysplasia in oral premalignant lesions using the Rose bengal stain. (no comparison between the two stains were intended )</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">27</enrollment>
  <condition>Oral Leukoplakia</condition>
  <condition>Oral Lichen Planus</condition>
  <condition>Premalignant Lesion</condition>
  <arm_group>
    <arm_group_label>Rose Bengal positive lesion and biopsy</arm_group_label>
    <description>Lesions that were stained positive with rose bengal were biopsied and assessed for dysplasia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Toluidine blue positive lesion and biopsy</arm_group_label>
    <description>Lesions that were stained positive with toluidine blue were biopsied and assessed for dysplasia</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biopsy</intervention_name>
    <description>rose bengal stain and toluidine is applied over a premalignant lesion and positively stained lesions are subjected to biopsy.</description>
    <arm_group_label>Rose Bengal positive lesion and biopsy</arm_group_label>
    <arm_group_label>Toluidine blue positive lesion and biopsy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Rose Bengal</intervention_name>
    <description>the lesions stained positive were subjected to biopsy</description>
    <arm_group_label>Rose Bengal positive lesion and biopsy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>toluidine blue</intervention_name>
    <description>the lesions stained positive were subjected to biopsy</description>
    <arm_group_label>Toluidine blue positive lesion and biopsy</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Biopsy specimen of the lesion was retained.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study group consists of 41 oral premalignant lesions in patients visiting the&#xD;
        Department of Oral Medicine and Radiology of The Oxford Dental College and Hospital,&#xD;
        Bangalore.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with clinically diagnosed oral premalignant lesions (oral leukoplakia and&#xD;
             oral lichen planus).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with OSMF&#xD;
&#xD;
          -  bleeding disorders and&#xD;
&#xD;
          -  other systemic diseases&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <results_first_submitted>February 2, 2017</results_first_submitted>
  <results_first_submitted_qc>March 6, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">November 5, 2018</results_first_posted>
  <last_update_submitted>March 6, 2018</last_update_submitted>
  <last_update_submitted_qc>March 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Oxford Dental College, Hospital and Research Center, Bangalore, India</investigator_affiliation>
    <investigator_full_name>Anisha Ramachandra Yaji</investigator_full_name>
    <investigator_title>doctor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Precancerous Conditions</mesh_term>
    <mesh_term>Leukoplakia</mesh_term>
    <mesh_term>Leukoplakia, Oral</mesh_term>
    <mesh_term>Lichen Planus, Oral</mesh_term>
    <mesh_term>Lichen Planus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tolonium Chloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>patients were recruited from the outpatient department of the dental college where the study was conducted.</recruitment_details>
      <pre_assignment_details>3 patients were excluded as one patient had not quit the habit and in another patient the lesion regressed during 2 weeks waiting period post habit cessation</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Study Participants</title>
          <description>All patients received Rose Bengal and Toluidine Blue. Initially patients were asked to rinse their mouth with distilled water for 1 minute. 1% RB solution was applied with a cotton tip for 2 minutes. Again patients were asked to rinse their mouth for 1 minute with distilled water to remove excess RB solution and the area which had taken up the stain was photographed. Following this, patients were asked to rinse their mouth with 1% acetic acid for 1 min to remove the remaining RB stain from the lesion and were prepared for TB staining. 1% Toluidine blue was applied over the same lesion and after 30 seconds patients were made to swish with 1% acetic acid and the area stained was photographed.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>lesion disappeared after stopping habit</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>all the patients who had premalignant lesions and had stopped using tobacco in the past two weeks</population>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>All study participants received Rose Bengal and Toulidine Blue. Patients were asked to rinse their mouth with distilled water for 1 minute. 1% RB solution was applied with a cotton tip for 2 minutes. Again patients were asked to rinse their mouth for 1 minute with distilled water to remove excess RB solution and the area which had taken up the stain was photographed. Following this, patients were asked to rinse their mouth with 1% acetic acid for 1 min to remove the remaining RB stain from the lesion and were prepared for TB staining. 1% Toluidine blue was applied over the same lesion and after 30 seconds patients were made to swish with 1% acetic acid and the area stained was photographed.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
          </count_list>
        </analyzed>
        <analyzed>
          <units>lesions</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="38"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>a proforma was used to record the baseline details</description>
          <units>lesions</units>
          <param>Count of Units</param>
          <units_analyzed>lesions</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.16" spread="9.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>lesions</units>
          <param>Count of Units</param>
          <units_analyzed>lesions</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>tobacco habit</title>
          <description>patients were asked regarding the usage of tobacco products and was recorded in proforma by investigator</description>
          <units>lesions</units>
          <param>Count of Units</param>
          <units_analyzed>lesions</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>location of the lesion</title>
          <units>lesions</units>
          <param>Count of Units</param>
          <units_analyzed>lesions</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>buccal mucosa</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>labial mucosa</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>tongue</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>gingiva</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number and Percentage of Lesions That Were Stained Positive</title>
        <description>outcome measure1</description>
        <time_frame>2 weeks</time_frame>
        <population>patients diagnosed with premalignant lesions who consented to participate in the study</population>
        <group_list>
          <group group_id="O1">
            <title>Rose Bengal Staining</title>
            <description>Initially patients were asked to rinse their mouth with distilled water for 1 minute. 1% RB solution was applied with a cotton tip for 2 minutes. Again patients were asked to rinse their mouth for 1 minute with distilled water to remove excess RB solution and the area which had taken up the stain was photographed. positively stained lesions were subjected for biopsy.</description>
          </group>
          <group group_id="O2">
            <title>Toluidine Blue Staining</title>
            <description>Following RB staining, patients were asked to rinse their mouth with 1% acetic acid for 1 min to remove the remaining RB stain from the lesion and were prepared for TB staining. 1% Toluidine blue was applied over the same lesion and after 30 seconds patients were made to swish with 1% acetic acid and the area stained was photographed. positively stained lesions were subjected to biopsy.</description>
          </group>
        </group_list>
        <measure>
          <title>Number and Percentage of Lesions That Were Stained Positive</title>
          <description>outcome measure1</description>
          <population>patients diagnosed with premalignant lesions who consented to participate in the study</population>
          <units>lesions</units>
          <param>Count of Units</param>
          <units_analyzed>lesions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>lesions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Rose bengal should stain the areas positively stained by Toluidine blue&#xD;
areas stained by rose bengal that shows dysplasia in biopsy</non_inferiority_desc>
            <p_value>0.005</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Sensitivity and Specificity (Percentage of True Positives and True Negatives)</title>
        <description>sensitivity: Percentage of lesions stained positive with Toluidine blue stain that were also stained positive with Rose Bengal stain specificity: Percentage of lesions stained negative with Toluidine blue stain that were also stained negative with Rose Bengal stain</description>
        <time_frame>2 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Study Participants</title>
            <description>1% RB solution was applied with a cotton tip for 2 minutes. Again patients were asked to rinse their mouth for 1 minute with distilled water to remove excess RB solution and the area which had taken up the stain was photographed.8 Following this, patients were asked to rinse their mouth with 1% acetic acid for 1 min to remove the remaining RB stain from the lesion.&#xD;
1% toluidine blue applied over the lesion and after 30 seconds were made to swish with 1% acetic acid. the area retaining the stain was photographed and compared with that of rose bengal. only positively stained areas were subjected to biopsy procedure.</description>
          </group>
        </group_list>
        <measure>
          <title>Sensitivity and Specificity (Percentage of True Positives and True Negatives)</title>
          <description>sensitivity: Percentage of lesions stained positive with Toluidine blue stain that were also stained positive with Rose Bengal stain specificity: Percentage of lesions stained negative with Toluidine blue stain that were also stained negative with Rose Bengal stain</description>
          <units>percentage of lesions</units>
          <param>Number</param>
          <units_analyzed>lesions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>lesions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>sensitivity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>specificity</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Presence of Dysplasia in Biopsied Lesions That Were Stained by Rose Bengal</title>
        <description>this outcome measure was limited to the biopsied lesions.additionally, the intent of this outcome measure was only to study early detection of dysplasia in oral premalignant lesions using the Rose bengal stain. (no comparison between the two stains were intended )</description>
        <time_frame>2 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Rose Bengal Staining and Biopsy</title>
            <description>Patients were asked to rinse their mouth with distilled water for 1 minute. 1% RB solution was applied with a cotton tip for 2 minutes. Again patients were asked to rinse their mouth for 1 minute with distilled water to remove excess RB solution and the area which had taken up the stain was photographed. Positively stained lesions were biopsied.</description>
          </group>
        </group_list>
        <measure>
          <title>Presence of Dysplasia in Biopsied Lesions That Were Stained by Rose Bengal</title>
          <description>this outcome measure was limited to the biopsied lesions.additionally, the intent of this outcome measure was only to study early detection of dysplasia in oral premalignant lesions using the Rose bengal stain. (no comparison between the two stains were intended )</description>
          <units>lesions</units>
          <param>Count of Units</param>
          <units_analyzed>lesions</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>lesions</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>dysplasia present</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>dysplasia absent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>squamous cell carcinoma</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>14th day from the date of recruitment</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Rose Bengal Positive Lesion</title>
          <description>lesions were subjected to rose bengal staining and positive lesions were subjected to biopsy</description>
        </group>
        <group group_id="E2">
          <title>Toluidine Blue Positive Lesions and Biopsy</title>
          <description>lesions were subjected to toluidine blue staining and positive lesions were subjected to biopsy</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="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </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="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </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>small sample size&#xD;
only lesions stained positive were selected for biopsy procedure hence interpretation of the staining was limited to certain lesions only&#xD;
a colorimetric guide was not used measure the intensity of staining</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Anisha Yaji</name_or_title>
      <organization>The Oxford Dental college</organization>
      <phone>9480718531</phone>
      <email>dr.anishayaji@gmail.com</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/NCT03031899
org study id: 219/2014-15
nct id: NCT03031899
lead sponsor: 
has dmc: Yes
Abstract

      Objective:

      To study the diagnostic efficiency of Rose Bengal with Toluidine blue in detecting the biopsy
      sites and thus establish an accurate diagnosis in oral premalignant lesions.

      Materials and method:

      In our study 27 patients with 41 lesions were included. Since one patient had not quit the
      habit in the two weeks following initial examination and another lesion disappeared in the
      waiting period, 2 patients (3 lesions) were not included in the study. Out of 38 lesions
      diagnosed based on clinical criteria, 32 were leukoplakia, 5 lichen planus and 1 SCC. After
      initial examination they were subjected to Rose Bengal and Toluidine blue stain. If stained
      positive they were subjected to biopsy.
Introduction Toluidine blue staining is the most common technique used for the early
      detection of dysplastic changes in patients with premalignant lesions. One meta-analysis of
      Rosenberg et al. previously published reported sensitivity ranged from 93.5% to 97.8% and the
      specificity ranged from 73.3% to 92.9%. Zang et al reported that TB not only detects
      high-grade dysplasia but detects OPLs with minimal or no dysplasia with high-risk clinical
      and molecular attributes.4 But, studies have shown as high as 30% risk of false-positive
      staining.

      Rose Bengal (RB) has been widely used to diagnose various ocular surface disorders including
      delineation of the extent of corneal and conjunctival neoplasms. It has been believed to
      stain desquamated ocular epithelial cells, dead or degenerated cells, or wherever there is
      poor protection of the surface epithelium by the preocular tear ﬁlm rather than lack of cell
      vitality. These characteristic features of RB lead the researchers to apply it in oral
      premalignant lesions.5 In none of the studies, reliability of RB stains was not compared with
      existing or previously practiced methods in oral premalignant lesions. Hence this study was
      undertaken with the aim of comparing the RB and TB stain and for early detection of dysplasia
      in oral premalignant lesions.

      Materials and Methods:

      Study group consists of 41 oral premalignant lesions in patients visiting the Department of
      Oral Medicine and Radiology of The oxford dental college and hospital, Bangalore. Patients
      with OSMF, patients with bleeding disorders, patient with other systemic diseases were
      excluded from the study.To perform the present study, ethical clearance was obtained from the
      Institutional Ethical Board. Study procedure was explained and informed consent was taken
      from the selected patients with premalignant lesions. The patients with lesions were
      subjected to detailed case history, intra oral examination and photographs of the lesions
      were recorded. Patients with habits were counselled to quit the habit and recalled after 2
      weeks for staining. Since one patient had not quit the habit in the two weeks from first
      visit, in another patient the lesion disappeared in two weeks 2 patients (3 lesions) were not
      included in the study. (Graph1)

      Initially patients were asked to rinse their mouth with distilled water for 1 minute. 1% RB
      solution was applied with a cotton tip for 2 minutes. Again patients were asked to rinse
      their mouth for 1 minute with distilled water to remove excess RB solution and the area which
      had taken up the stain was photographed. Following this, patients were asked to rinse their
      mouth with 1% acetic acid for 1 min to remove the remaining RB stain from the lesion and were
      prepared for TB staining. 1%Toluidineblue is applied over the lesion and after 30 seconds
      patients were made to swish with 1% acetic acid and the area stained was recorded
      photographically.

      These two photographs were assessed and if the stained area was similar in both the
      procedures single biopsy was taken. If the stained areas were different two different
      biopsies were taken.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Number and Percentage of Lesions That Were Stained Positive
time frame: 2 weeks
description: outcome measure1
measure: Sensitivity and Specificity (Percentage of True Positives and True Negatives)
time frame: 2 weeks
description: sensitivity: Percentage of lesions stained positive with Toluidine blue stain that were also stained positive with Rose Bengal stain specificity: Percentage of lesions stained negative with Toluidine blue stain that were also stained negative with Rose Bengal stain
measure: Presence of Dysplasia in Biopsied Lesions That Were Stained by Rose Bengal
time frame: 2 weeks
description: this outcome measure was limited to the biopsied lesions.additionally, the intent of this outcome measure was only to study early detection of dysplasia in oral premalignant lesions using the Rose bengal stain. (no comparison between the two stains were intended )
arm group label: Rose Bengal positive lesion and biopsy
description: Lesions that were stained positive with rose bengal were biopsied and assessed for dysplasia
arm group label: Toluidine blue positive lesion and biopsy
description: Lesions that were stained positive with toluidine blue were biopsied and assessed for dysplasia
intervention type: Procedure
intervention name: Biopsy
description: rose bengal stain and toluidine is applied over a premalignant lesion and positively stained lesions are subjected to biopsy.
arm group label: Rose Bengal positive lesion and biopsy
arm group label: Toluidine blue positive lesion and biopsy
intervention type: Diagnostic Test
intervention name: Rose Bengal
description: the lesions stained positive were subjected to biopsy
arm group label: Rose Bengal positive lesion and biopsy
intervention type: Diagnostic Test
intervention name: toluidine blue
description: the lesions stained positive were subjected to biopsy
arm group label: Toluidine blue positive lesion and biopsy
Biopsy specimen of the lesion was retained.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: The Oxford Dental College, Hospital and Research Center, Bangalore, India
investigator full name: Anisha Ramachandra Yaji
investigator title: doctor
mesh term: Precancerous Conditions
mesh term: Leukoplakia
mesh term: Leukoplakia, Oral
mesh term: Lichen Planus, Oral
mesh term: Lichen Planus
mesh term: Tolonium Chloride
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: small sample size
only lesions stained positive were selected for biopsy procedure hence interpretation of the staining was limited to certain lesions only
a colorimetric guide was not used measure the intensity of staining
point of contact: 