The Vaginal Health Trial

June 13, 2018 updated by: Katherine Guthrie, Fred Hutchinson Cancer Center

The Vaginal Health Trial - Effects of Vaginal Estradiol Tablet and Moisturizing Gel on Postmenopausal Vaginal Symptoms

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

302

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Washington
      • Seattle, Washington, United States, 98101
        • Kaiser Permanente Washington Health Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

43 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
Other Names:
  • vaginal estradiol
Other: Placebo gel
Dispensed in visually identical tube and gel form to Replens.
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.
Device: Replens
2.5 gm to be applied vaginally every 3 days over 12 weeks.
Other Names:
  • non-hormonal hydrophilic non-prescriptive vaginal gel
Other: Placebo tablet
Dispensed in visually identical bottle and tablet form to Vagifem.
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).
Other: Placebo gel
Dispensed in visually identical tube and gel form to Replens.
Other: Placebo tablet
Dispensed in visually identical bottle and tablet form to Vagifem.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, Week 4, Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, Week 4, Week 12
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.
Baseline, Week 4, Week 12
Treatment Satisfaction
Time Frame: Week 12
Likert Scale 0 = no to 10 = complete satisfaction.
Week 12
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).
Week 12
pH
Time Frame: Week 12
Objective measures of genitourinary atrophy: pH (<5 or >5) at week 12
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
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

Massachusetts General Hospital
University of California, San Diego
University of Washington
University of Minnesota
Kaiser Permanente

Investigators

  • Principal Investigator: Susan D Reed, MD, University of Washington
  • Principal Investigator: Caroline Mitchell, MD, MPH, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2016

Primary Completion (Actual)

May 1, 2017

Study Completion (Actual)

July 1, 2017

Study Registration Dates

First Submitted

August 3, 2015

First Submitted That Met QC Criteria

August 3, 2015

First Posted (Estimate)

August 5, 2015

Study Record Updates

Last Update Posted (Actual)

July 12, 2018

Last Update Submitted That Met QC Criteria

June 13, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MsFLASH 05
  • 8378 (FHCRC IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

The MsFLASH Data Coordinating Center will perform the statistical analyses for the primary and secondary study results papers. Within a 12-month period after publication of the main study results, the Data Coordinating Center will prepare datasets for public release that include all data elements in the main publication with certain deletions and recoding to protect study subject confidentiality. The public release datasets will include substantial documentation in electronic form, thus allowing external investigators to independently analyze the data.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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