Randomized trial of multi-strain Lactobacillus crispatus vaginal live biotherapeutic products after antibiotic therapy for bacterial vaginosis: study protocol for VIBRANT (vaginal lIve biotherapeutic RANdomized trial)
Callin Chetty, Nomfuneko A. Mafunda, Anna‐Ursula Happel, Anam Khan, Briah Cooley Demidkina, Nonhlanhla Yende‐Zuma, Yusra Saidi, Asthu Mahabeer Polliah, Lara Lewis, Farzana Osman, Precious Radebe, Jo-Ann S. Passmore, Doug Kwon, Jacques Ravel, Sinaye Ngcapu, Lenine J. P. Liebenberg, Laura Symul, Susan Holmes, Caroline M. Mitchell, Disebo Potloane
Abstract
Globally, approximately 30% of women have bacterial vaginosis (BV). Antibiotic treatment is frequently followed by recurrence, likely due to lack of colonization with beneficial lactobacilli. This is a Phase 1, randomized, placebo-controlled trial of vaginal live biotherapeutic products (LBP) after antibiotic treatment for BV to establish Lactobacillus colonization. The LBP are vaginal tablets containing 6 L. crispatus strains (LC106) or 15 L. crispatus strains (LC115), at 2 x 10 9 colony forming units (CFU) per dose. Participants with BV in the United States and South Africa will receive seven days of oral metronidazole twice daily and will be randomized 1:1:1:1:1 to: seven days placebo; seven days LC106; three days LC106/four days placebo; seven days LC106 starting day 3 of the metronidazole course; or seven days LC115. Safety will be assessed by the number and percentage of > Grade 2 related adverse events during or after product use. The primary outcome is LBP colonization defined as relative abundance ≥5% of any LBP strain or ≥10% of a combination of LBP strains by metagenomic sequencing any time in the 5 weeks after randomization. A generalized linear model will measure the association between treatment group and colonization, adjusting for site. This study seeks to establish proof of concept for a multi-strain LBP to promote vaginal L. crispatus colonization in two geographically distinct populations. South African National Clinical Trials Registry (SANCTR DOH-27-102023-8342; October 27, 2023) and ClinicalTrials.gov (NCT06135974; November 11, 2023). 2.0 dated October 03, 2023 Strengths: • This study is the first Phase 1 trial to assess multi-strain Lactobacillus crispatus LPBs. • This study is set in two distinct geographical locations (United States and South Africa), allowing for greater generalizability of results. Limitations: • This study’s sample size was calculated to detect a difference in colonization between the placebo arm and each individual LBP arm. It will not have power to detect a difference between the two LBPs (LC106 and LC115) or between dosing strategies for LC106. • Since the study is conducted across two sites, standardization of demographics questionnaires across sites is a challenge. Questionnaires assessing socio-economic status and race ethnicity are developed according to each site. • One arm of the trial is unblinded, due to a difference in the timing of dispensing study product.