The Vaginal Health Trial

Menopause Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02516202
• Other study ID #: MsFLASH 05
• Secondary ID: 8378
• Status: Completed
• Phase: Phase 3
• Start date: April 2016
• Est. completion date: July 2017

Study information

• Verified date: June 2018
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 302
• Est. completion date: July 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Atrophy
• Atrophy of Vagina
• Dyspareunia
• Dyspareunia (Female)
• Menopause

Intervention

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.
• Placebo gel
Dispensed in visually identical tube and gel form to Replens.

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota
United States	Kaiser Permanente Washington Health Research Institute	Seattle	Washington

Sponsors (7)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	Kaiser Permanente, Kaiser Permanente Washington Health Research Institute, Massachusetts General Hospital, University of California, San Diego, University of Minnesota - Clinical and Translational Science Institute, University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Week 4, Week 12
Secondary	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.	Baseline, Week 4, Week 12
Secondary	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.	Baseline, Week 4, Week 12
Secondary	Treatment Satisfaction	Likert Scale 0 = no to 10 = complete satisfaction.	Week 12
Secondary	Patient Benefit Evaluation	Patient Benefit Evaluation: Overall, do you believe that you experienced a meaningful benefit from the study medication? (Yes/No).	Week 12
Secondary	pH	Objective measures of genitourinary atrophy: pH (<5 or >5) at week 12	Week 12
Secondary	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	Week 12

External Links

•   Fred Hutchinson Cancer Research Center website