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


BACKGROUND
ClinicalTrials.gov NCT00850837.
Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, United States of America. marla.keller@einstein.yu.edu
Marla J
MJ
Keller
Colleen A
CA
Carpenter
Yungtai
Y
Lo
Mark H
MH
Einstein
Congzhou
C
Liu
David N
DN
Fredricks
Betsy C
BC
Herold
D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D002021:Buffers; D002584:Cervix Uteri / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D005260:Female; D058869:Gynecological Examination; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018836:Inflammation Mediators / Q000378:metabolism; D019344:Lactic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D054892:Metagenome / Q000187:drug effects; D008875:Middle Aged; D012449:Safety; D013089:Spermatocidal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D013997:Time Factors; D014621:Vagina / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D014622:Vaginal Creams, Foams, and Jellies; D055815:Young Adult; D016903:Drug Monitoring
D000890:Anti-Infective Agents; D002021:Buffers; D018836:Inflammation Mediators; D013089:Spermatocidal Agents; D014622:Vaginal Creams, Foams, and Jellies; D019344:Lactic Acid