The goal of this randomized clinical trial is to evaluate safety and biologic effect of a multi-strain vaginal L. crispatus live biotherapeutic product (LBP) in people receiving antibiotic treatment for bacterial vaginosis (BV). The main question\[s\] it aims to answer are whether the intervention is safe, and whether the strains of L. crispatus will colonize recipients' vagina. The study will evaluate one LBP with 6 strains of L. crispatus (LC106) and one LBP with 15 strains (LC115) vs. placebo. Participants will: * be treated with oral antibiotics for BV * receive 7 days of vaginal study product * collect daily home swabs and make short daily diary entries for 5 weeks, including the week of antibiotic treatment and the week of study product treatment. Researchers will compare the 3 groups receiving different dosing strategies of LC106 and 1 group receiving LC115 vs. 1 group receiving placebo to see if the live biotherapeutic strains colonize the vagina after antibiotic treatment for BV.
This is a Phase I randomized trial of a novel live biotherapeutic intervention containing multiple strains of L. crispatus. L. crispatus is a species of Lactobacillus commonly found in the human vagina, which is associated with optimal reproductive health outcomes. Detection of, and dominance of the community by, L. crispatus is associated with lower risk for bacterial vaginosis (BV), but no intervention to date has demonstrated the ability to durably shift the vaginal microbiome to L. crispatus dominance in a majority of treated people. In this study, we will compare safety and biologic effects of two formulations of a consortia of L. crispatus strains, and a variety of dosing strategies in women with BV who receive antibiotic treatment. Our primary outcome is colonization with any of the L. crispatus strains contained in the live biotherapeutic product. All participants will have menses suppressed with either injectable progesterone contraception or continuous oral contraceptive pills for the duration of the study. All participants will receive 7 days of oral metronidazole (500mg twice daily) and will be randomized to one of five groups: 1. Placebo daily for 7d after metronidazole treatment 2. LC-106 daily for 7d after metronidazole treatment 3. LC-106 daily for 3d + 4 days of placebo, starting after metronidazole treatment 4. LC-106 daily for 7d, starting on day 3 of metronidazole treatment 5. LC-115 daily for 7d after metronidazole treatment
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
24
Tablet containing at least 2 x 10\^6 CFU/tablet, and comprised of 6 strains of Lactobacillus crispatus
Tablet containing at least 2 x 10\^6 CFU/tablet, and comprised of 15 strains of Lactobacillus crispatus
Vaginal tablets containing primarily microcrystalline cellulose and no live bacteria
Metronidazole tablet orally twice daily for 7 days
Massachusetts General Hospital
Boston, Massachusetts, United States
CAPRISA - Vulindlela
Msunduzi Municipality, KwaZulu-Natal, South Africa
Detection of LBP strains by metagenomic sequencing
Detection of any one strain from the LBP at 5% relative abundance or greater, or any combination of strains at 10% relative abundance or greater using shotgun metagenomic sequencing
Time frame: Over 5 weeks
Adverse events
Assessment of safety by comparing number and severity of adverse events
Time frame: Over 12 weeks
Kinetics of colonization
Presence and quantity of each strain contained in the LBP measured by strain-specific quantitative PCR
Time frame: Over 12 weeks
Recurrent BV by Amsel and Nugent criteria
Presence of BV by Amsel criteria and/or Nugent criteria
Time frame: Over 12 weeks
Non-iners Lactobacillus dominance and abundance
Using 16S rRNA sequencing, relative abundance of non-iners Lactobacillus species in the vaginal fluid, and proportion with dominance by these species (\> 50% relative abundance)
Time frame: Over 12 weeks
Alpha and beta diversity of the microbial community
Comparison of alpha and beta diversity metrics between arms before and after treatment with LBP
Time frame: Over 12 weeks
Proportion of participants reporting product was acceptable to use
Participant perceptions of and preferences for the vaginal LBP treatment
Time frame: Over 12 weeks
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