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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
Sponsor:
Collaborators:
University of Minnesota - Clinical and Translational Science Institute
Massachusetts General Hospital
University of California, San Diego
University of Washington
Kaiser Permanente
Information provided by (Responsible Party):
Katherine Guthrie, Fred Hutchinson Cancer Research Center

Brief 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.

Condition or disease Intervention/treatment Phase
Atrophy of Vagina Menopause Dyspareunia (Female) Drug: Vagifem Device: Replens Other: Placebo tablet Other: Placebo gel Phase 3

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  (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

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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.


  2. 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.

  3. Treatment Satisfaction [ Time Frame: Week 12 ]
    Likert Scale 0 = no to 10 = complete satisfaction.

  4. 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).

  5. pH [ Time Frame: Week 12 ]
    Objective measures of genitourinary atrophy: pH (<5 or >5) at week 12

  6. 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



Information from the National Library of Medicine

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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
Criteria

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)

Information from the National Library of Medicine

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


Locations
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
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
University of Minnesota - Clinical and Translational Science Institute
Massachusetts General Hospital
University of California, San Diego
University of Washington
Kaiser Permanente
Investigators
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
  Study Documents (Full-Text)

Documents provided by Katherine Guthrie, Fred Hutchinson Cancer Research Center:
Informed Consent Form  [PDF] November 1, 2016


Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Katherine Guthrie, Principal Investigator, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT02516202     History of Changes
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
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Atrophy
Dyspareunia
Pathological Conditions, Anatomical
Sexual Dysfunction, Physiological
Genital Diseases, Male
Genital Diseases, Female
Sexual Dysfunctions, Psychological
Mental Disorders
Estradiol
Polyestradiol phosphate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Psyllium
Calcium polycarbophil
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Cathartics
Gastrointestinal Agents
Antidiarrheals