Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive

Abstract

Background: Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota.

Methods: Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays.

Results: The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08).

Conclusions: Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels of antimicrobial (lactoferrin) and anti-inflammatory (IL-1ra) proteins. These findings indicate the need for additional safety studies of this candidate non-hormonal contraceptive.

Trial registration: ClinicalTrials.gov NCT00850837.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Trial profile.

Figure 2. The pH of the vagina and cervix was significantly lower 2 hours after application of Acidform compared to HEC placebo gel.

Box-and-whisker plots showing the pH of the posterior fornix (a), lateral vaginal wall (b), cervix (c) and CVL (d) obtained at screening (Scr), 2 hours (2 h) and at Days 7, 14 and 21 after insertion of Acidform (white) or HEC placebo gel (gray). The line indicates the median values and the circles are outliers. The asterisks denote a significant difference between the Acidform and HEC placebo group.

Figure 3. The bactericidal activity of genital tract secretions against E. coli was significantly greater 2 hours after application of Acidform compared to HEC placebo gel.

Box-and-whisker plots showing the percent inhibition of E. coli (a) and HSV-2 plaque formation (b) in CVL samples collected at screening (Scr), 2 hours (2 h) and at Days 7, 14 and 21 after insertion of Acidform (white) or HEC placebo gel (gray). The line indicates the median values and the circles are outliers. The asterisk denotes a significant difference between the Acidform and HEC placebo group.