<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/NCT01663558</url>
  </required_header>
  <id_info>
    <org_study_id>23592103</org_study_id>
    <nct_id>NCT01663558</nct_id>
  </id_info>
  <brief_title>Anal Dysplasia Study of Men Who Have Sex With Men Living With HIV</brief_title>
  <official_title>Anal Dysplasia Study of Men Who Have Sex With Men Living With HIV</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>United States Naval Medical Center, San Diego</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>United States Naval Medical Center, San Diego</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Context:&#xD;
&#xD;
      Men who have sex with men (MSM) are at increased risk for HPV-related anal neoplasia and anal&#xD;
      squamous cell carcinoma; concomitant HIV infection roughly doubles that risk.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        1. To compare the efficacy of ablative therapy to topical imiquimod therapy in the&#xD;
           management of anal dysplasia in HIV-infected men.&#xD;
&#xD;
        2. To describe relationship between cytologic grade of anal dysplasia (as reported on&#xD;
           screening anal Pap test) and pathologic grade reported on anal mucosa histopathologic&#xD;
           examination.&#xD;
&#xD;
        3. To describe demographic, sexual practices, HPV-specific, and HIV-specific correlates of&#xD;
           anal dysplasia.&#xD;
&#xD;
        4. To describe adverse effects associated with ablative therapy and topical imiquimod&#xD;
           therapy.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Prospective, randomized controlled clinical trial. This will be a pilot study. All subjects&#xD;
      will undergo baseline anal Pap, HRA with biopsies as indicated, and anal HPV testing. If AIN&#xD;
      2 or 3 is discovered on histopathologic examination, subject will be offered observation only&#xD;
      or treatment. If he chooses treatment, he will be randomized to: 1) imiquimod anal&#xD;
      suppositories three times weekly for 3 months, or 2) appropriate ablative therapy as&#xD;
      determined by colorectal surgeon. During imiquimod treatment (not applicable to ablative&#xD;
      group as their treatment will be completed in one visit) subjects will be followed for 2&#xD;
      weeks, 4 weeks, 8 weeks, and 12 weeks with anal Pap, HRA with biopsies as indicated, and anal&#xD;
      HPV testing. After therapy completed in each treatment group, subjects will be followed for 1&#xD;
      month, 3 months, 6 months, 9 months, and 12 months post-therapy with anal Pap, HRA with&#xD;
      biopsies as indicated, and anal HPV testing. Observation only subjects will be evaluated&#xD;
      every 3 months with anal Pap, HRA with biopsies as indicated, and anal HPV testing for 12&#xD;
      months. We have chosen a goal of 30 subjects in each treatment group and 10 subjects in the&#xD;
      observation only group based on the likelihood of enrolling a study of this type in a&#xD;
      reasonable amount of time.&#xD;
&#xD;
      Main Outcome Measures:&#xD;
&#xD;
        1. Anal Pap cytologic grade, including regression and recurrence during course of study&#xD;
&#xD;
        2. HPV type in anal canal, including regression and recurrence during course of study&#xD;
&#xD;
        3. Anal histology, including regression and recurrence during course of study&#xD;
&#xD;
        4. Adverse effects experienced during treatment, recorded in symptom log&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    funding not available&#xD;
  </why_stopped>
  <start_date>May 2015</start_date>
  <completion_date type="Anticipated">May 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>cytologic grade</measure>
    <time_frame>3 months</time_frame>
    <description>Anal Pap cytologic grade, including regression and recurrence during course of study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HPV</measure>
    <time_frame>3 months</time_frame>
    <description>HPV type in anal canal, including regression and recurrence during course of study</description>
  </secondary_outcome>
  <other_outcome>
    <measure>histologic grade</measure>
    <time_frame>3 months</time_frame>
    <description>Anal histology, including regression and recurrence during course of study</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Anal Dysplasia</condition>
  <condition>Human Papilloma Virus</condition>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>imiquimod</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>i. Each subject will use an imiquimod anal suppository three times weekly (overnight on Monday, Wednesday, Friday) for 12 weeks.&#xD;
ii. Each subject will be asked to abstain from receptive anal sex during therapy period (12 weeks).&#xD;
iii. If local imiquimod adverse effects are severe, a 7-day period off of treatment will be permitted.&#xD;
iv. During 12 week therapy period, each subject will be evaluated 2, 4, 8, and 12 weeks after starting therapy. At each visit, subject will complete a therapy questionnaire and undergo anal Pap, HRA with biopsies as indicated, and anal HPV testing.&#xD;
v. After therapy completed (12 weeks), subject will enter 12 month observation period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ablative</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>i. Subject will be referred to colorectal surgeon, will complete a therapy questionnaire, and will be treated in accordance with treatment algorithm which is already in use.&#xD;
ii. Subject will be asked to abstain from receptive anal sex for 12 weeks after ablative therapy.&#xD;
iii. After therapy, subject will enter 12 month observation period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observation</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>i. Given lack of accepted guidelines and outcome data on dysplasia management, the study PI will thoroughly discuss risks and benefits of observation/monitoring and treatment of dysplasia.&#xD;
ii. If treatment is chosen, subject will be randomized to 1) ablative group, or 2) imiquimod group and begin therapy. Observation subjects will continue observation visits (observation questionnaire, anal Pap, HRA with biopsies as indicated, and anal HPV testing) every 3 months for 12 months (4 additional study visits).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>imiquimod</intervention_name>
    <arm_group_label>imiquimod</arm_group_label>
    <other_name>Aldara</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>ablative</intervention_name>
    <arm_group_label>ablative</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male gender, ≥18 years of age&#xD;
&#xD;
          -  HIV-infected and taking ARVs with suppressed HIV VL (&lt;48 copies/mL) on 2 consecutive&#xD;
             measurements within the previous 6 months&#xD;
&#xD;
          -  Any CD4 count will be considered appropriate for study&#xD;
&#xD;
          -  Plasma INR &lt; 1.5&#xD;
&#xD;
          -  Plasma partial thromboplastin time (PTT) &lt; 35s&#xD;
&#xD;
          -  Blood WBC &gt; 2.0x103/mm3 and absolute neutrophils count &gt; 500&#xD;
&#xD;
          -  Blood hemoglobin &gt; 10.0 g/dL&#xD;
&#xD;
          -  Blood platelet count &gt; 50x103/mm3&#xD;
&#xD;
          -  Serum total bilirubin &lt; 6.0 mg/dL (subjects taking atazanavir-based ARV regimens may&#xD;
             have elevated total bilirubin but are generally &lt; 6)&#xD;
&#xD;
          -  Blood aspartate aminotransferase (AST) &lt; 100 U/L (&lt;2 ULN)&#xD;
&#xD;
          -  Blood alanine aminotransferase (ALT) &lt; 130 U/L (&lt;2 ULN)&#xD;
&#xD;
          -  Serum creatinine &lt; 1.5 mg/dL&#xD;
&#xD;
          -  ECOG performance status &lt; 3&#xD;
&#xD;
          -  Tricare beneficiary&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of AIN&#xD;
&#xD;
          -  Anal canal condyloma requiring surgical treatment&#xD;
&#xD;
          -  Anal cancer (current or history of)&#xD;
&#xD;
          -  History of prior anal surgery, including hyfrecation, excision, cryotherapy,&#xD;
             photocoagulation&#xD;
&#xD;
          -  Use of anticoagulants (warfarin, heparin, Pradaxa)&#xD;
&#xD;
          -  Inability to attend study visits&#xD;
&#xD;
          -  Participation in any other drug study&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John D Malone, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>United States Naval Medical Center, San Diego</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NMCSD</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>August 9, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <last_update_submitted>August 18, 2016</last_update_submitted>
  <last_update_submitted_qc>August 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>anal dysplasia</keyword>
  <keyword>HPV</keyword>
  <keyword>HIV</keyword>
  <keyword>MSM</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Papilloma</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Imiquimod</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT01663558
org study id: 23592103
nct id: NCT01663558
lead sponsor: 
has dmc: No
Context:

      Men who have sex with men (MSM) are at increased risk for HPV-related anal neoplasia and anal
      squamous cell carcinoma; concomitant HIV infection roughly doubles that risk.

      Objectives:

        1. To compare the efficacy of ablative therapy to topical imiquimod therapy in the
           management of anal dysplasia in HIV-infected men.

        2. To describe relationship between cytologic grade of anal dysplasia (as reported on
           screening anal Pap test) and pathologic grade reported on anal mucosa histopathologic
           examination.

        3. To describe demographic, sexual practices, HPV-specific, and HIV-specific correlates of
           anal dysplasia.

        4. To describe adverse effects associated with ablative therapy and topical imiquimod
           therapy.

      Design:

      Prospective, randomized controlled clinical trial. This will be a pilot study. All subjects
      will undergo baseline anal Pap, HRA with biopsies as indicated, and anal HPV testing. If AIN
      2 or 3 is discovered on histopathologic examination, subject will be offered observation only
      or treatment. If he chooses treatment, he will be randomized to: 1) imiquimod anal
      suppositories three times weekly for 3 months, or 2) appropriate ablative therapy as
      determined by colorectal surgeon. During imiquimod treatment (not applicable to ablative
      group as their treatment will be completed in one visit) subjects will be followed for 2
      weeks, 4 weeks, 8 weeks, and 12 weeks with anal Pap, HRA with biopsies as indicated, and anal
      HPV testing. After therapy completed in each treatment group, subjects will be followed for 1
      month, 3 months, 6 months, 9 months, and 12 months post-therapy with anal Pap, HRA with
      biopsies as indicated, and anal HPV testing. Observation only subjects will be evaluated
      every 3 months with anal Pap, HRA with biopsies as indicated, and anal HPV testing for 12
      months. We have chosen a goal of 30 subjects in each treatment group and 10 subjects in the
      observation only group based on the likelihood of enrolling a study of this type in a
      reasonable amount of time.

      Main Outcome Measures:

        1. Anal Pap cytologic grade, including regression and recurrence during course of study

        2. HPV type in anal canal, including regression and recurrence during course of study

        3. Anal histology, including regression and recurrence during course of study

        4. Adverse effects experienced during treatment, recorded in symptom log
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: cytologic grade
time frame: 3 months
description: Anal Pap cytologic grade, including regression and recurrence during course of study
measure: HPV
time frame: 3 months
description: HPV type in anal canal, including regression and recurrence during course of study
measure: histologic grade
time frame: 3 months
description: Anal histology, including regression and recurrence during course of study
arm group label: imiquimod
arm group type: Active Comparator
description: i. Each subject will use an imiquimod anal suppository three times weekly (overnight on Monday, Wednesday, Friday) for 12 weeks.
ii. Each subject will be asked to abstain from receptive anal sex during therapy period (12 weeks).
iii. If local imiquimod adverse effects are severe, a 7-day period off of treatment will be permitted.
iv. During 12 week therapy period, each subject will be evaluated 2, 4, 8, and 12 weeks after starting therapy. At each visit, subject will complete a therapy questionnaire and undergo anal Pap, HRA with biopsies as indicated, and anal HPV testing.
v. After therapy completed (12 weeks), subject will enter 12 month observation period.
arm group label: ablative
arm group type: Active Comparator
description: i. Subject will be referred to colorectal surgeon, will complete a therapy questionnaire, and will be treated in accordance with treatment algorithm which is already in use.
ii. Subject will be asked to abstain from receptive anal sex for 12 weeks after ablative therapy.
iii. After therapy, subject will enter 12 month observation period.
arm group label: Observation
arm group type: No Intervention
description: i. Given lack of accepted guidelines and outcome data on dysplasia management, the study PI will thoroughly discuss risks and benefits of observation/monitoring and treatment of dysplasia.
ii. If treatment is chosen, subject will be randomized to 1) ablative group, or 2) imiquimod group and begin therapy. Observation subjects will continue observation visits (observation questionnaire, anal Pap, HRA with biopsies as indicated, and anal HPV testing) every 3 months for 12 months (4 additional study visits).
intervention type: Drug
intervention name: imiquimod
arm group label: imiquimod
other name: Aldara
intervention type: Procedure
intervention name: ablative
arm group label: ablative
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: John D Malone, MD
role: Principal Investigator
affiliation: United States Naval Medical Center, San Diego
facility: 
country: United States
responsible party type: Sponsor
mesh term: Papilloma
mesh term: Hyperplasia
mesh term: Imiquimod
sharing ipd: No