<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/NCT01709448</url>
  </required_header>
  <id_info>
    <org_study_id>1K23AI080202-01</org_study_id>
    <secondary_id>1K23AI080202-01</secondary_id>
    <nct_id>NCT01709448</nct_id>
  </id_info>
  <brief_title>Modeling Study to Predict Progression of Anal Cancer Pre-cursor Lesions in HIV</brief_title>
  <official_title>Predictive Modeling of Anal Dysplasia Progression in HIV</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Cincinnati</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cincinnati VA Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether a model can be created to predict the&#xD;
      progression of early anal cancer precursor lesions in HIV using potential predictors such as:&#xD;
      HIV treatment history, smoking history, sexual history, human papillomavirus viral load,&#xD;
      human papillomavirus protein expression, and cell markers associated with progression of&#xD;
      HPV-related lesions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Persons living with HIV-infection are at greatly increased risk for anal carcinoma and anal&#xD;
      intraepithelial neoplasia (AIN). Despite the overall improvement in HIV outcomes, the&#xD;
      incidence of anal carcinoma has not decreased with the advent of highly active antiretroviral&#xD;
      ther-apy. Further, there is substantial morbidity and mortality associated with anal&#xD;
      carcinoma in HIV-infected individuals. For these reasons, it is critically important to&#xD;
      develop effective screening and treatment strategies in this population. Anal carcinoma is&#xD;
      similar to cervical carcinoma in that they are both associated with infection with human&#xD;
      papillomavirus (HPV) and share similar cytologic features of dysplasia. Anal cytology&#xD;
      screening is ultimately expected to reduce the incidence of anal carcinoma similar to that&#xD;
      seen with cervical cancer after the introduction of cervical Pap screening. Given the high&#xD;
      frequency of abnormal cytology in patients with HIV and the need to confirm results by&#xD;
      high-resolution anoscopy, however, the implementation of screening programs requires a&#xD;
      substantial commitment of clinical resources. The workload and costs involved in following up&#xD;
      on abnormal cytology reduce the cost-effectiveness of screening and pose a significant&#xD;
      barrier to its widespread integration into routine HIV care. A model for predicting which&#xD;
      patients are at greatest risk for progressive of anal dysplasia is needed in order to&#xD;
      decrease the need for excessive confirmatory procedures in this population. Without such a&#xD;
      model, anal carcinoma screening may remain cost prohibitive for many HIV clinics.&#xD;
&#xD;
      The objective of this study is to develop a predictive model to identify patients who are at&#xD;
      greatest risk for progression of anal intraepithelial neoplastic changes. The central&#xD;
      hypotheses are: 1) that progression of early HPV-related anal dysplasia is associated with&#xD;
      environmental, virological, and host molecular factors and 2) that it is possible to develop&#xD;
      a predictive statistical model with a high sensitivity and specificity for predicting disease&#xD;
      progression. These hypotheses have been formulated on the basis of strong evidence from&#xD;
      studies of HPV-related cervical dysplasia that smoking, HPV E2 expression, HPV E6/E7 protein&#xD;
      expression, high-risk HPV type, HPV viral load, p16 expression, p53 expression and Ki67&#xD;
      expression are associated with progressive cervical dysplasia. The rationale for the proposed&#xD;
      research is that development of a predictive model will allow clinicians to design more&#xD;
      cost-effective screening and follow-up strategies which focus resources on intensively&#xD;
      testing only those patients with a significant risk for progression. Further, the models&#xD;
      developed will allow clinicians to identify a population of patients who may benefit from&#xD;
      early treatment interventions. Finally, information learned from this research may provide&#xD;
      information applicable to other HPV-related cancers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2009</start_date>
  <completion_date type="Anticipated">March 2014</completion_date>
  <primary_completion_date type="Anticipated">March 2014</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>histological diagnosis of high-grade squamous intra-epithelial lesion confirmed by anal biopsy</measure>
    <time_frame>12 months, 24 months, 36 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Regression of lesions defined by normal appearance on anoscopy and normal histology on anal biopsy following previous diagnosis of squamous intraepithelial lesion.</measure>
    <time_frame>12 months, 24 months, 36 months</time_frame>
  </secondary_outcome>
  <enrollment type="Anticipated">165</enrollment>
  <condition>Neoplasms, Squamous Cell</condition>
  <condition>Papillomavirus Infections</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Anal cytology Anal biopsies&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        HIV primary care clinic&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV-infected&#xD;
&#xD;
          -  Age &gt; 18 years old&#xD;
&#xD;
          -  Abnormal anal screening cytology&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to sign informed consent&#xD;
&#xD;
          -  Life-threatening illness or other contraindication for high-resolution anoscopy&#xD;
&#xD;
          -  anal intraepithelial neoplasia not confirmed by anal biopsy&#xD;
&#xD;
          -  history of anal carcinoma&#xD;
&#xD;
          -  history of HPV vaccination&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jaime C Robertson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cincinnati</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jaime C Robertson, MD</last_name>
    <phone>(513) 584-5827</phone>
    <email>roberj5@ucmail.uc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Eva Moore, RN</last_name>
    <phone>(513) 584-4819</phone>
    <email>mooreev@ucmail.uc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Cincinnati VA Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45225</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>George Smulian, MD</last_name>
      <phone>513-861-3100</phone>
      <phone_ext>4425</phone_ext>
      <email>smuliang@fuse.net</email>
    </contact>
    <contact_backup>
      <last_name>Diana Moore, ARNP</last_name>
      <phone>(513) 475-6599</phone>
      <email>Diana.Moore2@va.gov</email>
    </contact_backup>
    <investigator>
      <last_name>George Smulian, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Stephen Kralovic, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Diana Moore, ARNP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jaime C Robertson, MD</last_name>
      <phone>513-584-5827</phone>
      <email>roberj5@ucmail.uc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Eva Moore, RN</last_name>
      <phone>(513) 584-4819</phone>
      <email>mooreev@ucmail.uc.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Jaime C Robertson, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://intmed.uc.edu/divisions/infectious_diseases/</url>
    <description>University of Cincinnati - Division of Infectious Diseases</description>
  </link>
  <link>
    <url>http://www.cincinnati.va.gov/</url>
    <description>Cincinnati VA Medical Center</description>
  </link>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <last_update_submitted>October 16, 2012</last_update_submitted>
  <last_update_submitted_qc>October 16, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 18, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Cincinnati</investigator_affiliation>
    <investigator_full_name>Jaime Robertson</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Neoplasms, Squamous Cell</keyword>
  <keyword>Papillomavirus Infections</keyword>
  <keyword>HIV</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Papillomavirus Infections</mesh_term>
    <mesh_term>Neoplasms, Squamous Cell</mesh_term>
  </condition_browse>
  <!-- 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/NCT01709448
org study id: 1K23AI080202-01
secondary id: 1K23AI080202-01
nct id: NCT01709448
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to determine whether a model can be created to predict the
      progression of early anal cancer precursor lesions in HIV using potential predictors such as:
      HIV treatment history, smoking history, sexual history, human papillomavirus viral load,
      human papillomavirus protein expression, and cell markers associated with progression of
      HPV-related lesions.
Persons living with HIV-infection are at greatly increased risk for anal carcinoma and anal
      intraepithelial neoplasia (AIN). Despite the overall improvement in HIV outcomes, the
      incidence of anal carcinoma has not decreased with the advent of highly active antiretroviral
      ther-apy. Further, there is substantial morbidity and mortality associated with anal
      carcinoma in HIV-infected individuals. For these reasons, it is critically important to
      develop effective screening and treatment strategies in this population. Anal carcinoma is
      similar to cervical carcinoma in that they are both associated with infection with human
      papillomavirus (HPV) and share similar cytologic features of dysplasia. Anal cytology
      screening is ultimately expected to reduce the incidence of anal carcinoma similar to that
      seen with cervical cancer after the introduction of cervical Pap screening. Given the high
      frequency of abnormal cytology in patients with HIV and the need to confirm results by
      high-resolution anoscopy, however, the implementation of screening programs requires a
      substantial commitment of clinical resources. The workload and costs involved in following up
      on abnormal cytology reduce the cost-effectiveness of screening and pose a significant
      barrier to its widespread integration into routine HIV care. A model for predicting which
      patients are at greatest risk for progressive of anal dysplasia is needed in order to
      decrease the need for excessive confirmatory procedures in this population. Without such a
      model, anal carcinoma screening may remain cost prohibitive for many HIV clinics.

      The objective of this study is to develop a predictive model to identify patients who are at
      greatest risk for progression of anal intraepithelial neoplastic changes. The central
      hypotheses are: 1) that progression of early HPV-related anal dysplasia is associated with
      environmental, virological, and host molecular factors and 2) that it is possible to develop
      a predictive statistical model with a high sensitivity and specificity for predicting disease
      progression. These hypotheses have been formulated on the basis of strong evidence from
      studies of HPV-related cervical dysplasia that smoking, HPV E2 expression, HPV E6/E7 protein
      expression, high-risk HPV type, HPV viral load, p16 expression, p53 expression and Ki67
      expression are associated with progressive cervical dysplasia. The rationale for the proposed
      research is that development of a predictive model will allow clinicians to design more
      cost-effective screening and follow-up strategies which focus resources on intensively
      testing only those patients with a significant risk for progression. Further, the models
      developed will allow clinicians to identify a population of patients who may benefit from
      early treatment interventions. Finally, information learned from this research may provide
      information applicable to other HPV-related cancers.
observational model: Cohort
time perspective: Prospective
measure: histological diagnosis of high-grade squamous intra-epithelial lesion confirmed by anal biopsy
time frame: 12 months, 24 months, 36 months
measure: Regression of lesions defined by normal appearance on anoscopy and normal histology on anal biopsy following previous diagnosis of squamous intraepithelial lesion.
time frame: 12 months, 24 months, 36 months
Anal cytology Anal biopsies
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jaime C Robertson, MD
role: Principal Investigator
affiliation: University of Cincinnati
last name: Jaime C Robertson, MD
phone: (513) 584-5827
email: roberj5@ucmail.uc.edu
last name: Eva Moore, RN
phone: (513) 584-4819
email: mooreev@ucmail.uc.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
url: http://intmed.uc.edu/divisions/infectious_diseases/
description: University of Cincinnati - Division of Infectious Diseases
url: http://www.cincinnati.va.gov/
description: Cincinnati VA Medical Center
responsible party type: Principal Investigator
investigator affiliation: University of Cincinnati
investigator full name: Jaime Robertson
investigator title: Assistant Professor
mesh term: Papillomavirus Infections
mesh term: Neoplasms, Squamous Cell