The Vaginal Health Trial

Overview

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.

Full Title of Study: “The Vaginal Health Trial – Effects of Vaginal Estradiol Tablet and Moisturizing Gel on Postmenopausal Vaginal Symptoms”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: May 2017

Detailed Description

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.

Interventions

  • Drug: Vagifem
    • One tablet is to be inserted vaginally daily for 2 weeks, then 2 days/week for the remaining 10 weeks of the study.
  • Device: Replens
    • 2.5 gm to be applied vaginally every 3 days over 12 weeks.
  • Other: Placebo tablet
    • Dispensed in visually identical bottle and tablet form to Vagifem.
  • Other: Placebo gel
    • Dispensed in visually identical tube and gel form to Replens.

Arms, Groups and Cohorts

  • Active Comparator: Vagifem
    • One hundred participants will be randomized into the Vagifem® ‘active’ arm. These women will receive a bottle of Vagifem® tablets (estradiol 10 mcg). One tablet is to be inserted vaginally daily for 2 weeks, then 2 days/week for the remaining 10 weeks of the study. Vagifem® tablets contain 10.3 mcg of estradiol hemihydrate equivalent to 10 mcg of estradiol. The excipient (inactive) ingredients are hypromellose, lactose monohydrate, maize starch, and magnesium stearate. Vagifem® comes as a small white film-coated tablet. The coating is made of hypromellose and polyethylene glycol. A placebo gel visually similar to Replens composed of inert hydroxyethylcellulose gel (pH adjusted) applied every 3 days over entire 12 weeks.
  • Active Comparator: Replens
    • One hundred participants will be randomized into the Replens® ‘active’ arm. These women will receive a tube containing Replens® vaginal gel, with 2.5 gm applied vaginally every 3 days over 12 weeks. Replens® is a bioadhesive polycarbophil-based moisturizing vaginal gel containing; purified water (vehicle humectant), glycerin (moisturizer), mineral oil (as a moisturizer), polycarbophil and carbomer homopolymer type B (allow the product to stick to the vaginal wall), hydrogenated palm oil glyceride (moisturizer), sorbic acid (preservative, antimicrobial), methylparaben, sodium hydroxide (adjusts pH of product so it is suitable for vaginal use). A placebo tablet visually identical to Vagifem® is inserted daily for 2 weeks, then 2 days/week for remaining 10 weeks.
  • Placebo Comparator: Placebo
    • One hundred participants will be randomized into the ‘placebo’ arm of the study. This arm is comprised of two placebo preparations; placebo tablet and placebo gel applied on the same schedule as ‘active’ arms. The placebo tablet coating and excipient ingredients will be the same as are used for Vagifem®; the coating is made of hypromellose and polyethylene glycol and the excipient (inactive) ingredients are hypromellose, lactose monohydrate, maize starch, and magnesium stearate. Placebo gel. The product is an inert hydroxyethylcellulose gel (pH adjusted).

Clinical Trial Outcome Measures

Primary Measures

  • Most Bothersome Symptom (MBS) Severity
    • Time Frame: Baseline, Week 4, Week 12
    • Mean change from baseline to 12 weeks in the severity of the MBS on a scale of 0-3, better to worse.

Secondary Measures

  • Vaginal Symptoms Index
    • Time Frame: Baseline, Week 4, Week 12
    • 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.
  • Female Sexual Function Index
    • Time Frame: Baseline, Week 4, Week 12
    • 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.
  • Treatment Satisfaction
    • Time Frame: Week 12
    • Likert Scale 0 = no to 10 = complete satisfaction.
  • Patient Benefit Evaluation
    • Time Frame: Week 12
    • Patient Benefit Evaluation: Overall, do you believe that you experienced a meaningful benefit from the study medication? (Yes/No).
  • pH
    • Time Frame: Week 12
    • Objective measures of genitourinary atrophy: pH (<5 or >5) at week 12
  • Vaginal Maturation Index
    • Time Frame: Week 12
    • Objective Measures of Genitourinary Atrophy: Vaginal Maturation Index (VMI) described by % parabasal, intermediate, and superficial cells (≤ 5% or >5% superficial cells) at week 12

Participating in This Clinical Trial

Inclusion Criteria

  • Females aged 45-70 years
  • 2 or more years since last natural menstrual period, or surgical menopause (bilateral oophorectomy)
  • At least 1 vaginal symptom (inside or outside the vagina) reported from the following list, experienced in the past 30 days which is moderate or severe:
  • Dryness at least once a week
  • Itching at least once a week
  • Irritation at least once a week
  • Soreness/Pain at least once a week
  • Pain associated with sexual activity at least once
  • Signed informed consent

Exclusion Criteria

  • Current unexplained abnormal genital bleeding (or any unevaluated bleeding since menopause)
  • Currently pregnant, attempting pregnancy or breast feeding
  • Current acute vaginal infection (as indicated by wet mount at V1)
  • Pelvic or vaginal surgery in prior 60 days
  • Antibiotic use in the past 30 days
  • Women under age 55 with endometrial ablation
  • Women under age 55 with hysterectomy and at least one ovary
  • Current cancer treatment (exception basal or squamous skin cell cancers)
  • Current or past thromboembolic disease (pulmonary embolus or deep vein thrombosis, not including thrombophlebitis), myocardial infarction or stroke
  • Current severe liver disease
  • Current or past breast or endometrial cancer or pre-cancer
  • Blood clotting disorder (e.g., Factor V Leiden, prothrombin mutation, protein C, protein or antithrombin deficiency)
  • Porphyria
  • Current or past lichen sclerosus or lichen planus
  • History of adverse reaction to vaginal estrogen or Replens
  • Use of any systemic reproductive hormones (hormonal contraception, postmenopausal hormone therapies, SERMS) in the past 2 months
  • Use of hormonal contraception in the past year
  • Use of any type of vaginal estrogen product (however interested women will be allowed to join the study if they abstain from use during the month preceding enrollment)
  • Use of any type of vaginal moisturizer, douche, vaginal prebiotic or probiotic, or soap in the vagina in the past month (however interested women will be allowed to join the study if they abstain from use during the month preceding enrollment)
  • Unwilling to abstain from use of any non-study vaginal moisturizer, vaginal estrogen, douche, or soap in the vagina throughout the trial
  • Unable to follow instructions, complete questionnaires, or physically unable to place product in the vagina
  • Current participation in another drug trial or intervention study
  • Chronic vulvo-vaginal symptoms in the 5 years before menopause (defined as a vaginal or vulvar condition requiring more than 4 visits to a health care provider in a given year)

Gender Eligibility: Female

Minimum Age: 45 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Fred Hutchinson Cancer Research Center
  • Collaborator
    • University of Minnesota
  • Provider of Information About this Clinical Study
    • Principal Investigator: Katherine Guthrie, Principal Investigator – Fred Hutchinson Cancer Research Center
  • Overall Official(s)
    • Katherine A Guthrie, PhD, Principal Investigator, Fred Hutchinson Cancer Research Center
    • Susan D Reed, MD, Principal Investigator, University of Washington
    • Andrea Z LaCroix, PhD, Principal Investigator, University of California, San Diego
    • Caroline Mitchell, MD, MPH, Principal Investigator, Massachusetts General Hospital

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.