Anal Dysplasia Study of Men Who Have Sex With Men Living With HIV - Full Text View

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:

To compare the efficacy of ablative therapy to topical imiquimod therapy in the management of anal dysplasia in HIV-infected men.
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.
To describe demographic, sexual practices, HPV-specific, and HIV-specific correlates of anal dysplasia.
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:

Anal Pap cytologic grade, including regression and recurrence during course of study
HPV type in anal canal, including regression and recurrence during course of study
Anal histology, including regression and recurrence during course of study
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 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:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Imiquimod

U.S. FDA Resources

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

Primary Outcome Measures:

cytologic grade [ Time Frame: 3 months ]
Anal Pap cytologic grade, including regression and recurrence during course of study

Secondary Outcome Measures:

HPV [ Time Frame: 3 months ]
HPV type in anal canal, including regression and recurrence during course of study

Other Outcome Measures:

histologic grade [ Time Frame: 3 months ]
Anal histology, including regression and recurrence during course of study


Enrollment:	0
Study Start Date:	May 2015
Estimated Study Completion Date:	May 2016
Estimated Primary Completion Date:	December 2015 (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 (Adult, Senior)
Sexes 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

Locations


United States, California
NMCSD
San Diego, California, United States, 92134

Sponsors and Collaborators

United States Naval Medical Center, San Diego

Investigators


Principal Investigator:	John D Malone, MD	United States Naval Medical Center, San Diego

More Information


Responsible Party:	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 18, 2016
Individual Participant Data
Plan to Share IPD:	No

Keywords provided by United States Naval Medical Center, San Diego:


anal dysplasia HPV HIV MSM

Additional relevant MeSH terms:


Hyperplasia Papilloma Pathologic Processes Neoplasms, Squamous Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms	Imiquimod Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents Interferon Inducers

ClinicalTrials.gov processed this record on June 23, 2017