Clinical trial NCT01663558: Anal Dysplasia Study of Men Who Have Sex With Men Living With HIV
Official title: Anal Dysplasia Study of Men Who Have Sex With Men Living With HIV
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Anal Dysplasia
Human Papilloma Virus
HIV
Keywords: anal dysplasia
HPV
HIV
MSM
Lead sponsor: United States Naval Medical Center, San Diego
Sponsor class: FED
First posted: 2012-08-13
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility 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

Primary outcomes:
measure: cytologic grade
timeFrame: 3 months
Secondary outcomes:
measure: HPV
timeFrame: 3 months
Other outcomes:
measure: histologic grade
timeFrame: 3 months
Locations:
city: San Diego
country: United States
facility: NMCSD
state: California
Study officials:
affiliation: United States Naval Medical Center, San Diego
name: John D Malone, MD
role: PRINCIPAL_INVESTIGATOR
References: