This is a new application from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) Clinical Trials network. Here we propose to conduct a large multicenter trial comparing two common treatments, a vaginal hormone tablet and an over-the-counter gel, with placebo to evaluate their effects on bothersome vaginal symptoms and sexual function, and to create a biorepository of specimens for future translational, mechanistic research on the etiology of vaginal symptoms.
The Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) Clinical Trials network was established in 2009. By the end of 2014, the network completed 4 clinical trials testing 7 interventions in approximately 1000 women ages 40-62 with vasomotor (VMS) and other menopause symptoms. The current trial will evaluate a relatively understudied area of menopause - vaginal health and sexual function. This is a 3-arm, randomized, controlled, double-blind, clinical trial among postmenopausal women ages 45-70. Our primary aim is to evaluate the effectiveness of ultra-low dose vaginal estradiol (Vagifem 10 mcg), non-hormonal hydrophilic non-prescriptive vaginal gel (Replens) and placebo in reducing the Most Bothersome Symptom (MBS) severity. Choices for MBS include vulvovaginal itching, pain, dryness, irritation, or pain with penetration. Secondary aims include an evaluation of a composite score of vaginal symptoms, sexual function, treatment satisfaction, menopause quality of life, and objective measures of genitourinary atrophy. We will also create a biorepository of vaginal and blood specimens. In a subset of women, we will examine whether treatment response is related to: a) the post-menopausal vaginal microbiome; b) vaginal mucosal inflammation; and c) reproductive hormone profiles. The in-depth focus on the mechanisms associated with postmenopausal vaginal symptoms will use state of the art microbiologic techniques on longitudinally collected biologic specimens and will guide future translational studies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
302
One tablet is to be inserted vaginally daily for 2 weeks, then 2 days/week for the remaining 10 weeks of the study.
2.5 gm to be applied vaginally every 3 days over 12 weeks.
Dispensed in visually identical bottle and tablet form to Vagifem.
University of Minnesota
Minneapolis, Minnesota, United States
Kaiser Permanente Washington Health Research Institute
Seattle, Washington, United States
Most Bothersome Symptom (MBS) Severity
Mean change from baseline to 12 weeks in the severity of the MBS on a scale of 0-3, better to worse.
Time frame: Baseline, Week 4, Week 12
Vaginal Symptoms Index
Mean change from baseline to 12 weeks in composite Vaginal Symptoms Index (VSI). The VSI is a Modified Bachman scale measuring vulvovaginal itching, dryness, irritation, soreness, and pain with sexual activity among sexually active women, each rated 0=none to 3=severe, and then averaged for a total score of 0-3.
Time frame: Baseline, Week 4, Week 12
Female Sexual Function Index
Female Sexual Function Index (FSFI); Evaluate dyspareunia, sexual function and distress. A composite score from 2 (not sexually active and no desire) to 36 and 6 domains.
Time frame: Baseline, Week 4, Week 12
Treatment Satisfaction
Likert Scale 0 = no to 10 = complete satisfaction.
Time frame: Week 12
Patient Benefit Evaluation
Patient Benefit Evaluation: Overall, do you believe that you experienced a meaningful benefit from the study medication? (Yes/No).
Time frame: Week 12
pH
Objective measures of genitourinary atrophy: pH (\<5 or \>5) at week 12
Time frame: Week 12
Vaginal Maturation Index
Objective Measures of Genitourinary Atrophy: Vaginal Maturation Index (VMI) described by % parabasal, intermediate, and superficial cells (≤ 5% or \>5% superficial cells) at week 12
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Dispensed in visually identical tube and gel form to Replens.
Time frame: Week 12