Lubricant Investigation in Men to Inhibit Transmission of HPV Infection (LIMIT-HPV): design and methods for a randomised controlled trial

Abstract

IntroductionGay, bisexual and other men who have sex with men (gbMSM) have an increased risk of human papillomavirus (HPV) infection and HPV-associated diseases, such as anal cancer and anogenital warts. A carrageenan-based lubricant could prevent HPV infection, thereby reducing the disease burden in this population. This paper describes the protocol for the Lubricant Investigation in Men to Inhibit Transmission of HPV Infection (LIMIT-HPV) study, an ongoing randomised controlled trial (RCT), evaluating efficacy of a carrageenan-based personal lubricant in reducing type-specific anal HPV incidence and prevalence among sexually active gbMSM, efficacy by HIV status, safety and tolerability of the gel and participant adherence to the intervention.Methods and analysisThe study is a double-blinded, placebo-controlled RCT. Volunteer gbMSM 18 years and older are randomly assigned 1:1 to receive the treatment (a self-applied anal microbicide gel with carrageenan) or placebo (a self-applied placebo gel). At each visit, computerised questionnaires are used to collect data on sociodemographic and clinical variables, lifestyle, sexual behaviour and the gels’ safety and tolerability. At baseline and each follow-up visit (months 1, 2, 3, 6, 9 and 12), nurses collect anal specimens tested for 36 HPV types (linear array assay). HIV status is determined at baseline and 12 months. The primary outcome is incidence of type-specific anal HPV infection(s) undetected at baseline. Secondary outcomes are prevalence of type-specific anal HPV infection, safety, tolerability and adherence. We aim to recruit 380 participants to attain the study’s objectives. Data will be analysed using intention-to-treat and per-protocol approaches with subgroup analyses by HIV status.Ethics and disseminationEthics approval was obtained by the Research Ethics Boards of McGill University, the McGill University Health Centre, Concordia University and Centre Hospitalier de l’Université de Montréal. Trial results will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberNCT02354144.

Assessment of the possible inhibitory effect of carrageenan in human papillomavirus DNA testing by polymerase chain reaction amplification

“…Although samples from participants in the placebo arm were not inhibited in Experiment #3, in concentrated samples the internal control was not amplified in 3% of samples in the placebo arm, suggesting the presence of other inhibitors. For ongoing or recently completed studies evaluating carrageenan, 2,11–13 the current results provide reassurance that carrageenan infrequently inhibits the amplification of DNA, and carrageenan does not impede HPV DNA extraction.…”

Carrageenan as a Preventive Agent Against Human Papillomavirus Infection: A Narrative Review

“…26 The 3 protocols were also from North America. [27][28][29] For studies in humans, the sample size ranged from 13 to 348 for published studies 16,24 and from 13 to 380 for protocols. 27,28 Of the 16 in vitro (Table 1) and in vivo studies (Table 2), the majority used pseudovirion (PsV) as the source of HPV, 9,10,[12][13][14][15][16][17][18]20,22,23 whereas other studies used bovine papillomavirus type 1 (BPV1), 8 furin-cleaved PsV (fcPsV), 19 or virus-like particle (VLP) 21 in addition to PsV.…”

“…Results from ongoing or recently completed studies evaluating carrageenan could potentially provide more evidence for (or against) carrageenan's potential as a preventive agent against HPV. 25,[27][28][29] These ongoing or recently completed studies that tested carrageenan alone or carrageenan-combination products are discussed hereinafter.…”

“…A similar study, also conducted by our research group, the Lubricant Investigation in Men to Inhibit Transmission of HPV Infection (LIMIT-HPV), was designed to assess the efficacy of a carrageenan lubricant against incidence and prevalent anal HPV infections among gay, bisexual, and other men who have sex with men (gbMSM). 27 Sexually active gbMSM are randomized 1:1 to the carrageenan or placebo gel arm. GbMSM were instructed to use their assigned gel during intercourse for the duration of the study (12-month follow-up period).…”

Protamine Sulfate Is a Potent Inhibitor of Human Papillomavirus InfectionIn VitroandIn Vivo

“…For example, the CATCH clinical trials showed a 36% reduction in newly acquired HPV infection in women who had applied carrageenan-containing gels ( 67 ). However, there have been safety concerns and absence of protective effects with carrageenan against anal HPV infections ( 39 , 68 ). Another carrageenan study (ClinicalTrials registration no.…”