Microbicide Safety and Acceptability in Young Men (Project Gel)

• Stage 1AB Primary behavioral outcomes [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Identification of factors related to acceptability and adherence
  • Proportion of participants who report via the acceptability questionnaire that they would be very likely to use a similar candidate microbicide gel during receptive anal intercourse (RAI)
  • Proportion of RAI episodes in which the gel was used
  • Comparison between self-reports of placebo gel use and applicator counts in Stage 1B
  
  
• Stage 1AB Primary clinical outcome [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  the presence of STIs and anal and rectal pathologies as detected by standard anoscopy
  
  
• Stage 2 Primary clinical outcomes [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  Grade 2 or higher AEs, as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 and/or Addenda 3 (Rectal Grading Tables for Use in Microbicide Studies).
  
  

• Stage 1AB Secondary clinical endpoint [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  Percent of agreement between reports of anal and rectal pathologies by two assessment methods (standard anoscopy versus high-resolutions anoscopy).
  
  
• Stage 2 Secondary behavioral outcomes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Identification of factors related to sexual behaviors (e.g., douching, lubricant use, recreational drug use, condom use, partner selection)
  • Prevalence of risky sexual practices, douching, lubricant use, recreational drug use, and condom use
  
  
• Stage 1AB Secondary behavioral outcomes [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Identification of factors related to sexual behaviors (e.g., condom use, lubricant use, douching, risky sexual practices, and recreational drug use)
  • Prevalence of condom use, lubricant use, douching, risky sexual practices, and recreational drug use
  
  

Microbicides are products that can be applied in the vagina or rectum to decrease the chances of transmission of sexually transmitted infections (STIs) including HIV. In the US, one of the most vulnerable groups for acquiring HIV infection is young men, especially young Black and Latino men who have sex with men (MSM). This study will be conducted with a young 18-30 year-old ethnically diverse sample of HIV-negative MSM who report engaging in receptive anal intercourse (RAI) using condoms inconsistently or not at all. Our goal is to test whether patterns of use of a placebo rectal gel prior to RAI suggest that the product would be used correctly and consistently in real life circumstances and whether this highly vulnerable population could safely use tenofovir gel, a microbicide candidate. The University of Pittsburgh is the coordinating center for this study; a separate coordinating center protocol for Stage 1AB was approved by the IRB on 10/13/10 under IRB#1009001, and the Stage 2 modification is pending. This study will be conducted by the University of Pittsburgh in collaboration with researchers at the HIV Center for Clinical and BehavioralStudies at Columbia University; the Fenway Community Health in Boston; and the University of Puerto Rico Clinical Trial Unit in San Juan, Puerto Rico. Subjects will be enrolled at the University of Pittsburgh, Fenway Community Health, and the University of Puerto Rico. This is a two-stage longitudinal study including a clinical and behavioral evaluation (Stage 1A) with an acceptability and adherence trial (Stage 1B), followed by a Phase 1 randomized, double-blind, multi-site, placebo-controlled trial (Stage 2). Participants who complete Stage 1A are eligible to be selected for enrollment into Stage 1B; a similar transition occurs between Stage 1B and Stage 2.

• In Stage 1A, 240 eligible participants (approximately 80 at each site) will undergo a baseline medical evaluation and a detailed Web-based baseline behavioral assessment. The first 120 eligible participants (approximately 40 at each site) reporting at least one occasion of unprotected RAI in the previous 3 months will continue onto the acceptability and adherence stage of the study (Stage 1B).
• In Stage 1B, participants will be asked to apply a placebo gel (HEC) rectally prior to each episode of RAI over a 3-month period, reporting each use via a phone reporting system. At the end of the 3 months, participants will complete a Web-based questionnaire and take part in a video teleconference.The first 42 eligible participants (approximately 14 at each site) completing Stage 1B with a reported adherence of 80% or greater will be invited to enroll in Stage 2.
• In Stage 2, participants will be randomized to receive either tenofovir 1% gel or HEC placebo gel. Following a baseline visit, participants will return to the clinic, where a single dose of the study gel will be administered. Within approximately 30 minutes, rectal swab, stool, and rectal biopsy specimens will be obtained via anoscopy. After a one-week recovery period participants will return to the clinic for assessment. If no significant adverse events (AEs) are reported they will begin to self-administer once-daily outpatient doses of the study gel for 7 days, after which they will return to the clinic for evaluation and specimen collection. The Full Board of the NY State Psychiatric Institute IRB, which oversees research conducted at the HIV Center for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University, convened on May 3, 2010 to determine whether the rectal applicator we will use in this study poses a significant risk to humans. Based on the Food and Drug Administration's definition of a Significant Risk Device, the Full Board determined that the rectal applicator is a non-significant risk device and does not require an IDE (NYSPI IRB Protocol #6169; letter attached under References and Other Attachments).