Anal Dysplasia Study of Men Who Have Sex With Men Living With HIV

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2013 by United States Naval Medical Center, San Diego
Sponsor:
Information provided by (Responsible Party):
Robert Carpenter, United States Naval Medical Center, San Diego
ClinicalTrials.gov Identifier:
NCT01663558
First received: August 9, 2012
Last updated: August 15, 2013
Last verified: August 2013
  Purpose

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

Condition Intervention Phase
Anal Dysplasia
Human Papilloma Virus
HIV
Drug: imiquimod
Procedure: ablative
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Anal Dysplasia Study of Men Who Have Sex With Men Living With HIV

Resource links provided by NLM:


Further study details as provided by United States Naval Medical Center, San Diego:

Primary Outcome Measures:
  • cytologic grade [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Anal Pap cytologic grade, including regression and recurrence during course of study


Secondary Outcome Measures:
  • HPV [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    HPV type in anal canal, including regression and recurrence during course of study


Other Outcome Measures:
  • histologic grade [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Anal histology, including regression and recurrence during course of study


Estimated Enrollment: 70
Study Start Date: December 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: imiquimod

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.

Drug: imiquimod
Other Name: Aldara
Active Comparator: ablative

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.

Procedure: ablative
No Intervention: Observation

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).


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male gender, ≥18 years of age
  • HIV-infected and taking ARVs with suppressed HIV VL (<48 copies/mL) on 2 consecutive measurements within the previous 6 months
  • Any CD4 count will be considered appropriate for study
  • Plasma INR < 1.5
  • Plasma partial thromboplastin time (PTT) < 35s
  • Blood WBC > 2.0x103/mm3 and absolute neutrophils count > 500
  • Blood hemoglobin > 10.0 g/dL
  • Blood platelet count > 50x103/mm3
  • Serum total bilirubin < 6.0 mg/dL (subjects taking atazanavir-based ARV regimens may have elevated total bilirubin but are generally < 6)
  • Blood aspartate aminotransferase (AST) < 100 U/L (<2 ULN)
  • Blood alanine aminotransferase (ALT) < 130 U/L (<2 ULN)
  • Serum creatinine < 1.5 mg/dL
  • ECOG performance status < 3
  • Tricare beneficiary

Exclusion Criteria:

  • History of AIN
  • Anal canal condyloma requiring surgical treatment
  • Anal cancer (current or history of)
  • History of prior anal surgery, including hyfrecation, excision, cryotherapy, photocoagulation
  • Use of anticoagulants (warfarin, heparin, Pradaxa)
  • Inability to attend study visits
  • Participation in any other drug study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01663558

Contacts
Contact: Patricia Schiffler 619-532-6251 patricia.schiffler@med.navy.mil

Locations
United States, California
NMCSD Not yet recruiting
San Diego, California, United States, 92103
Sponsors and Collaborators
United States Naval Medical Center, San Diego
Investigators
Principal Investigator: Robert J. Carpenter, DO FACP NMCSD
  More Information

No publications provided

Responsible Party: Robert Carpenter, pricipal investigator, United States Naval Medical Center, San Diego
ClinicalTrials.gov Identifier: NCT01663558     History of Changes
Other Study ID Numbers: 23592103
Study First Received: August 9, 2012
Last Updated: August 15, 2013
Health Authority: United States: Federal Government

Keywords provided by United States Naval Medical Center, San Diego:
anal dysplasia
HPV
HIV
MSM

Additional relevant MeSH terms:
Papilloma
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Imiquimod
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Interferon Inducers

ClinicalTrials.gov processed this record on September 11, 2014