The Vaginal Health Trial
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ClinicalTrials.gov Identifier: NCT02516202 |
Recruitment Status :
Completed
First Posted : August 5, 2015
Results First Posted : July 12, 2018
Last Update Posted : July 12, 2018
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Condition or disease | Intervention/treatment | Phase |
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Atrophy of Vagina Menopause Dyspareunia (Female) | Drug: Vagifem Device: Replens Other: Placebo tablet Other: Placebo gel | Phase 3 |
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 (Clinical Trial) |
Actual Enrollment : | 302 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | The Vaginal Health Trial - Effects of Vaginal Estradiol Tablet and Moisturizing Gel on Postmenopausal Vaginal Symptoms |
Actual Study Start Date : | April 2016 |
Actual Primary Completion Date : | May 2017 |
Actual Study Completion Date : | July 2017 |

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 Name: 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 Name: 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 tablet
Dispensed in visually identical bottle and tablet form to Vagifem. Other: Placebo gel Dispensed in visually identical tube and gel form to Replens. |
- 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.
- 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

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Ages Eligible for Study: | 45 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
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)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02516202
United States, Minnesota | |
University of Minnesota | |
Minneapolis, Minnesota, United States, 55455 | |
United States, Washington | |
Kaiser Permanente Washington Health Research Institute | |
Seattle, Washington, United States, 98101 |
Principal Investigator: | Katherine A Guthrie, PhD | Fred Hutchinson Cancer Research Center | |
Principal Investigator: | Susan D Reed, MD | University of Washington | |
Principal Investigator: | Andrea Z LaCroix, PhD | University of California, San Diego | |
Principal Investigator: | Caroline Mitchell, MD, MPH | Massachusetts General Hospital |
Documents provided by Katherine Guthrie, Fred Hutchinson Cancer Research Center:
Responsible Party: | Katherine Guthrie, Principal Investigator, Fred Hutchinson Cancer Research Center |
ClinicalTrials.gov Identifier: | NCT02516202 |
Other Study ID Numbers: |
MsFLASH 05 8378 ( Other Identifier: FHCRC IRB ) |
First Posted: | August 5, 2015 Key Record Dates |
Results First Posted: | July 12, 2018 |
Last Update Posted: | July 12, 2018 |
Last Verified: | June 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
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. |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | Yes |
Dyspareunia Atrophy Pathological Conditions, Anatomical Sexual Dysfunction, Physiological Sexual Dysfunctions, Psychological Mental Disorders |
Estradiol Estrogens Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |