Phase 1 Dose-Ranging Safety Trial of Lactobacillus crispatus CTV-05 for the Prevention of Bacterial Vaginosis

Abstract

Background Bacterial vaginosis is a very common vaginal infection. The lack of endogenous lactobacilli and overgrowth of pathogens facilitate numerous gynecological complications. Methods A phase I dose-ranging safety trial tested the safety, tolerability and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) administered by vaginal applicator. Twelve healthy volunteers were enrolled in three blocks of four (5 × 108, 1 × 109 and 2 × 109 cfu/dose). Each block was randomized in a 3:1 ratio of active product to placebo. Participants used study product for 5 consecutive days, returned for follow up on Days 7 and 14, and had phone interviews on Days 2 and 35. Results All 12 participants took 5 doses and completed study follow-up. Overall, 45 adverse events (AEs) occurred, of which 31 (69%) were genitourinary (GU) AEs. GU AEs appeared evenly distributed between the three treatment blocks and between LACTIN-V and placebo arms. The most common GU AEs were vaginal discharge in 5 subjects (42%), abdominal pain in 4 subjects (33%), metrorrhagia in 4 subjects (33%), vulvovaginitis in 4 subjects (33%), vaginal candidiasis in 3 subjects (25%), and vaginal odor in 3 subjects (25%). Forty one (91%) AEs were mild (grade 1) in severity. All four moderate AEs (grade 2) were unrelated to product use. No grade 3 or 4 AEs or serious adverse events (SAE) occurred. Laboratory parameters and colposcopy findings were within normal limits or clinically insignificant. The product was well tolerated and accepted. Conclusion All three dose levels of LACTIN-V appeared to be safe and acceptable in healthy volunteers.

Nanoparticle-based drug delivery to the vagina: A review

“…Approximately one-third of all women have BV at any given time, a fraction that is increased in certain populations of women at high risk of acquiring sexually transmitted infections [44]. Thus, changes in the vaginal environment caused by BV may be particularly important to consider when designing microbicide products.…”

Sexually transmitted infections: challenges ahead

“…Effectiveness of chlamydia screening in clinical trials 307 The rationale for chlamydia screening is that testing should detect asymptomatic infections in 308 women before they cause PID or other reproductive complications; if a large enough 309 proportion of the population can be screened, reduced incidence and prevalence of infection 310 ought to further prevent reproductive complications indirectly by reducing exposure to 311 infection. 91 …”

Exploring a Road Map to Counter Misconceptions About the Cervicovaginal Microbiome and Disease

“…54 As BV is a risk factor for HIV, rather than use microbicides that are toxic to the epithelium, the administration of lactobacilli and extended periods of maintenance of microbial homeostasis might also be worth pursuing to prevent HIV. Whether probiotics can also decrease the risk of HIV in women infected with human papilloma virus (HPV), itself a risk factor (new ref 55) remains to be seen, but one study suggests that HPV positive women treated with L. rhamnosus GR-1 and L. reuteri RC-14 have lower incidence of BV (new ref 56). The potential for long-term maintenance of a lactobacilli-dominated vagina is being explored with L crispatus CTV05.…”

“…56 In addition, there needs to be a consensus drawn on what tests can be done in different settings (private practice, clinics, hospitals, rural areas), what information can be gained from each, and how to interpret the findings. When symptoms are reported, on-site wet mount microscopy is arguably the most revealing in diagnosing AV, BV, or yeast infection and a normal condition, 14 and, contrary to common perception, the learning curve of fresh wet mount microscopy is relatively short, provided proper training is administered (Donders et al, submitted for publication).…”