<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/NCT04472455</url>
  </required_header>
  <id_info>
    <org_study_id>2017-347</org_study_id>
    <nct_id>NCT04472455</nct_id>
  </id_info>
  <brief_title>Mobile High-Resolution Microendoscopy (mHRME) for the Detection of Cervical Dysplasia in El Salvador</brief_title>
  <official_title>Mobile High-Resolution Microendoscopy (mHRME) for the Detection of Cervical Dysplasia in El Salvador</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>William Marsh Rice University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Basic Health International</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Albert Einstein College of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>William Marsh Rice University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Evaluate the performance of the mHRME in a study of 3,000 women in San Salvador to assess&#xD;
      whether mHRME imaging improves specificity of screening by VIA or HPV DNA without reducing&#xD;
      sensitivity for cervical precancer and cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective cohort study. Eligibility is open to women 30-49 years old, who are not&#xD;
      pregnant, have an intact cervix, and no history of cervical cancer.&#xD;
&#xD;
      Visit 1:&#xD;
&#xD;
      Patients will enroll at the screening clinic of the Instituto del Cáncer de El Salvador (El&#xD;
      Salvador Cancer Institute, ICES). An informed consent will be obtained. They will be given a&#xD;
      urine pregnancy test; if negative, two cervical samples will be collected. The first sample&#xD;
      will be used to screen for HPV DNA. New technologies to screen for oncoproteins and HPV will&#xD;
      be applied to the second sample. 3-5% acetic acid will also be applied to the cervix to&#xD;
      perform the VIA. Images of the cervix will be taken and any personally identifiable&#xD;
      information removed.&#xD;
&#xD;
      Visit 2:&#xD;
&#xD;
      All women with a positive VIA or HPV test will undergo additional evaluation. In addition,&#xD;
      10% of women in the double negative group (VIA-/HPV-) will be randomly selected for&#xD;
      evaluation. This evaluation includes: Urine pregnancy test, VIA, colposcopy, Lugol's solution&#xD;
      application, and a HRME. 3-5% acetic acid will be applied to the cervix to perform the VIA.&#xD;
      Proflavine and Lugol's solution (2-5%) will be applied and once again the health care&#xD;
      provider will record their impression for each of the abnormal lesions. Cervical images will&#xD;
      be taken. Then, 0.01% proflavine will be topically applied to the cervix for 1 minute. Images&#xD;
      will be obtained using the mHRME system of a visually normal site and then of all lesions&#xD;
      identified by VIA, colposcopy, and/or Lugol's solution. If no lesions are identified by VIA,&#xD;
      colposcopy, and/or Lugol's solution, mHRME images will be taken of each quadrant. Samples of&#xD;
      abnormal areas identified by VIA, colposcopy, Lugol's solution, and/or mHRME will be&#xD;
      collected for biopsy and ECC purposes. If the evaluation shows no abnormalities, a random&#xD;
      sample will be collected from the squamocolumnar junction and an ECC will be performed (only&#xD;
      if the patient is HPV positive). Two expert pathologists will review and classify the&#xD;
      samples. All research results will be unbeknownst to them. They will use the following&#xD;
      classification system: normal, CIN 1, CIN 2, CIN 3, AIS, or cancer, per standard criteria.&#xD;
      Discrepant results are resolved by a third expert pathologist, with the final result being&#xD;
      based on 2/3 agreement. If all three pathologists arrive at different diagnoses, all three&#xD;
      will meet in person to review to reach a consensus diagnosis. Women with CIN 2+ will undergo&#xD;
      an excision or cryotherapy, according to the treatment standard. Patients diagnosed with&#xD;
      invasive cancer will be referred to gynecology/oncology.&#xD;
&#xD;
      The sensitivity, specificity, positive predictive value, and negative predictive value for&#xD;
      each screening and triage method will be compared using histopathology as the gold standard.&#xD;
      These results will enable us to compare the total number of women that could have received&#xD;
      adequate and inadequate treatment based on five of the most predominant clinical scenarios:&#xD;
      VIA alone, VIA/mHRME triage, HPV test alone, HPV/VIA triage, and HPV/mHRME triage.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2015</start_date>
  <completion_date type="Actual">April 2, 2019</completion_date>
  <primary_completion_date type="Actual">April 2, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Accuracy of mHRME to detect CIN2+</measure>
    <time_frame>1-2 days</time_frame>
    <description>Calculate the sensitivity, specificity, positive predictive value, and negative predictive value of mHRME to detect CIN2+.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of different screening and triage strategies to detect CIN2+</measure>
    <time_frame>1-2 days</time_frame>
    <description>Compare the sensitivities and specificities of the following theoretical strategies to detect CIN2+: VIA alone, VIA/mHRME triage, HPV test alone, HPV/VIA triage, and HPV/mHRME triage.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">1827</enrollment>
  <condition>Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>Screen Negative Group</arm_group_label>
    <description>All women who screen negative at Visit 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Screen Positive Group</arm_group_label>
    <description>All women who screened positive at Visit 1 and were invited to Visit 2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>10% Of Screen Negative Group</arm_group_label>
    <description>10% of women who screened negative at Visit 1 and were invited to Visit 2</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>HRME</intervention_name>
    <arm_group_label>10% Of Screen Negative Group</arm_group_label>
    <arm_group_label>Screen Negative Group</arm_group_label>
    <arm_group_label>Screen Positive Group</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Cervical swab samples are collected to test for HPV DNA&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This is a prospective cohort study. Eligibility is open to women 30-49 years old, who are&#xD;
        not pregn ant, have an intact cervix and no history of cervical cancer&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women who are between the ages of 30 and 49 years of age&#xD;
&#xD;
          2. All women must have a negative urine or serum pregnancy test prior to any study&#xD;
             procedure (within 7 days)&#xD;
&#xD;
          3. Intact cervix (patients who have undergone previous LEEP, cone and/ or cryotherapy are&#xD;
             not eligible)&#xD;
&#xD;
          4. No history of invasive cervical cancer&#xD;
&#xD;
          5. Able and willing to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women &lt; 30 years of age or over 49 years of age&#xD;
&#xD;
          2. Women who have undergone a hysterectomy with removal of the cervix&#xD;
&#xD;
          3. Women who have had a previous LEEP, Cold knife cone and/or cryotherapy&#xD;
&#xD;
          4. Women who are pregnant or breastfeeding&#xD;
&#xD;
          5. Women with a history of invasive cervical cancer&#xD;
&#xD;
          6. Unable or unwilling to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mauricio Maza, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Basic Health International</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rebecca Richards-Kortum, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>William Marsh Rice University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kathleen Schmeler, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
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  <verification_date>June 2020</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>July 10, 2020</last_update_submitted>
  <last_update_submitted_qc>July 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 15, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>William Marsh Rice University</investigator_affiliation>
    <investigator_full_name>Rebecca Richards-Kortum</investigator_full_name>
    <investigator_title>Malcolm Gillis University Professor, Professor of Bioengineering</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Dysplasia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>REDCap platform will be used to share data.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT04472455/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04472455
org study id: 2017-347
nct id: NCT04472455
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Evaluate the performance of the mHRME in a study of 3,000 women in San Salvador to assess
      whether mHRME imaging improves specificity of screening by VIA or HPV DNA without reducing
      sensitivity for cervical precancer and cancer.
This is a prospective cohort study. Eligibility is open to women 30-49 years old, who are not
      pregnant, have an intact cervix, and no history of cervical cancer.

      Visit 1:

      Patients will enroll at the screening clinic of the Instituto del Cáncer de El Salvador (El
      Salvador Cancer Institute, ICES). An informed consent will be obtained. They will be given a
      urine pregnancy test; if negative, two cervical samples will be collected. The first sample
      will be used to screen for HPV DNA. New technologies to screen for oncoproteins and HPV will
      be applied to the second sample. 3-5% acetic acid will also be applied to the cervix to
      perform the VIA. Images of the cervix will be taken and any personally identifiable
      information removed.

      Visit 2:

      All women with a positive VIA or HPV test will undergo additional evaluation. In addition,
      10% of women in the double negative group (VIA-/HPV-) will be randomly selected for
      evaluation. This evaluation includes: Urine pregnancy test, VIA, colposcopy, Lugol's solution
      application, and a HRME. 3-5% acetic acid will be applied to the cervix to perform the VIA.
      Proflavine and Lugol's solution (2-5%) will be applied and once again the health care
      provider will record their impression for each of the abnormal lesions. Cervical images will
      be taken. Then, 0.01% proflavine will be topically applied to the cervix for 1 minute. Images
      will be obtained using the mHRME system of a visually normal site and then of all lesions
      identified by VIA, colposcopy, and/or Lugol's solution. If no lesions are identified by VIA,
      colposcopy, and/or Lugol's solution, mHRME images will be taken of each quadrant. Samples of
      abnormal areas identified by VIA, colposcopy, Lugol's solution, and/or mHRME will be
      collected for biopsy and ECC purposes. If the evaluation shows no abnormalities, a random
      sample will be collected from the squamocolumnar junction and an ECC will be performed (only
      if the patient is HPV positive). Two expert pathologists will review and classify the
      samples. All research results will be unbeknownst to them. They will use the following
      classification system: normal, CIN 1, CIN 2, CIN 3, AIS, or cancer, per standard criteria.
      Discrepant results are resolved by a third expert pathologist, with the final result being
      based on 2/3 agreement. If all three pathologists arrive at different diagnoses, all three
      will meet in person to review to reach a consensus diagnosis. Women with CIN 2+ will undergo
      an excision or cryotherapy, according to the treatment standard. Patients diagnosed with
      invasive cancer will be referred to gynecology/oncology.

      The sensitivity, specificity, positive predictive value, and negative predictive value for
      each screening and triage method will be compared using histopathology as the gold standard.
      These results will enable us to compare the total number of women that could have received
      adequate and inadequate treatment based on five of the most predominant clinical scenarios:
      VIA alone, VIA/mHRME triage, HPV test alone, HPV/VIA triage, and HPV/mHRME triage.
observational model: Cohort
time perspective: Prospective
measure: Accuracy of mHRME to detect CIN2+
time frame: 1-2 days
description: Calculate the sensitivity, specificity, positive predictive value, and negative predictive value of mHRME to detect CIN2+.
measure: Comparison of different screening and triage strategies to detect CIN2+
time frame: 1-2 days
description: Compare the sensitivities and specificities of the following theoretical strategies to detect CIN2+: VIA alone, VIA/mHRME triage, HPV test alone, HPV/VIA triage, and HPV/mHRME triage.
arm group label: Screen Negative Group
description: All women who screen negative at Visit 1.
arm group label: Screen Positive Group
description: All women who screened positive at Visit 1 and were invited to Visit 2
arm group label: 10% Of Screen Negative Group
description: 10% of women who screened negative at Visit 1 and were invited to Visit 2
intervention type: Diagnostic Test
intervention name: HRME
arm group label: 10% Of Screen Negative Group
arm group label: Screen Negative Group
arm group label: Screen Positive Group
Cervical swab samples are collected to test for HPV DNA
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 30 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mauricio Maza, MD
role: Principal Investigator
affiliation: Basic Health International
last name: Rebecca Richards-Kortum, PhD
role: Principal Investigator
affiliation: William Marsh Rice University
last name: Kathleen Schmeler, MD
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
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responsible party type: Principal Investigator
investigator affiliation: William Marsh Rice University
investigator full name: Rebecca Richards-Kortum
investigator title: Malcolm Gillis University Professor, Professor of Bioengineering
mesh term: Uterine Cervical Dysplasia
sharing ipd: Yes
ipd description: REDCap platform will be used to share data.
provided document: 