NCT02516202

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
302

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Apr 2016

Shorter than P25 for phase_3

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 3, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 5, 2015

Completed
8 months until next milestone

Study Start

First participant enrolled

April 1, 2016

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2017

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2017

Completed
1 year until next milestone

Results Posted

Study results publicly available

July 12, 2018

Completed
Last Updated

July 12, 2018

Status Verified

June 1, 2018

Enrollment Period

1.1 years

First QC Date

August 3, 2015

Results QC Date

May 7, 2018

Last Update Submit

June 13, 2018

Conditions

Atrophy of VaginaMenopauseDyspareunia (Female)

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (6)

  • Vaginal Symptoms Index

    Baseline, Week 4, Week 12

  • Female Sexual Function Index

    Baseline, Week 4, Week 12

  • Treatment Satisfaction

    Week 12

  • Patient Benefit Evaluation

    Week 12

  • pH

    Week 12

  • +1 more secondary outcomes

Study Arms (3)

Vagifem

ACTIVE COMPARATOR

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: VagifemOther: Placebo gel

Replens

ACTIVE COMPARATOR

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: ReplensOther: Placebo tablet

Placebo

PLACEBO COMPARATOR

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 tabletOther: Placebo gel

Interventions

VagifemDRUG

One tablet is to be inserted vaginally daily for 2 weeks, then 2 days/week for the remaining 10 weeks of the study.

Also known as: vaginal estradiol
Vagifem
ReplensDEVICE

2.5 gm to be applied vaginally every 3 days over 12 weeks.

Also known as: non-hormonal hydrophilic non-prescriptive vaginal gel
Replens
Placebo tabletOTHER

Dispensed in visually identical bottle and tablet form to Vagifem.

PlaceboReplens
Placebo gelOTHER

Dispensed in visually identical tube and gel form to Replens.

PlaceboVagifem

Eligibility Criteria

Age45 Years - 70 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Females aged 45-70 years
  • 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

You may not qualify if:

  • 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
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Kaiser Permanente Washington Health Research Institute

Seattle, Washington, 98101, United States

Location

Related Publications (8)

  • Mitchell CM, Larson JC, Reed SD, Guthrie KA. The complexity of genitourinary syndrome of menopause: number, severity, and frequency of vulvovaginal discomfort symptoms in women enrolled in a randomized trial evaluating treatment for genitourinary syndrome of menopause. Menopause. 2023 Aug 1;30(8):791-797. doi: 10.1097/GME.0000000000002212. Epub 2023 Jul 4.

    PMID: 37402281DERIVED

  • Mitchell CM, Larson JC, Crandall CJ, Bhasin S, LaCroix AZ, Ensrud KE, Guthrie KA, Reed SD. Association of Vaginal Estradiol Tablet With Serum Estrogen Levels in Women Who Are Postmenopausal: Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2022 Nov 1;5(11):e2241743. doi: 10.1001/jamanetworkopen.2022.41743.

    PMID: 36374501DERIVED

  • Srinivasan S, Hua X, Wu MC, Proll S, Valint DJ, Reed SD, Guthrie KA, LaCroix AZ, Larson JC, Pepin R, Bhasin S, Raftery D, Fredricks DN, Mitchell CM. Impact of Topical Interventions on the Vaginal Microbiota and Metabolome in Postmenopausal Women: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2022 Mar 1;5(3):e225032. doi: 10.1001/jamanetworkopen.2022.5032.

    PMID: 35353163DERIVED

  • Mitchell CM, Ma N, Mitchell AJ, Wu MC, Valint DJ, Proll S, Reed SD, Guthrie KA, Lacroix AZ, Larson JC, Pepin R, Raftery D, Fredricks DN, Srinivasan S. Association between postmenopausal vulvovaginal discomfort, vaginal microbiota, and mucosal inflammation. Am J Obstet Gynecol. 2021 Aug;225(2):159.e1-159.e15. doi: 10.1016/j.ajog.2021.02.034. Epub 2021 Mar 4.

    PMID: 33675793DERIVED

  • Hudson PL, Ling W, Wu MC, Hayward MR, Mitchell AJ, Larson J, Guthrie KA, Reed SD, Kwon DS, Mitchell CM. Comparison of the Vaginal Microbiota in Postmenopausal Black and White Women. J Infect Dis. 2021 Dec 1;224(11):1945-1949. doi: 10.1093/infdis/jiaa780.

    PMID: 33367735DERIVED

  • Mitchell CM, Guthrie KA, Larson J, Diem S, LaCroix AZ, Caan B, Shifren JL, Woods NF, Heiman JR, Lindau ST, Reed SD. Sexual frequency and pain in a randomized clinical trial of vaginal estradiol tablets, moisturizer, and placebo in postmenopausal women. Menopause. 2019 Aug;26(8):816-822. doi: 10.1097/GME.0000000000001341.

    PMID: 30994576DERIVED

  • Diem SJ, Guthrie KA, Mitchell CM, Reed SD, Larson JC, Ensrud KE, LaCroix AZ. Effects of vaginal estradiol tablets and moisturizer on menopause-specific quality of life and mood in healthy postmenopausal women with vaginal symptoms: a randomized clinical trial. Menopause. 2018 Oct;25(10):1086-1093. doi: 10.1097/GME.0000000000001131.

    PMID: 29738424DERIVED

  • Mitchell CM, Reed SD, Diem S, Larson JC, Newton KM, Ensrud KE, LaCroix AZ, Caan B, Guthrie KA. Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial. JAMA Intern Med. 2018 May 1;178(5):681-690. doi: 10.1001/jamainternmed.2018.0116.

    PMID: 29554173DERIVED

Related Links

MeSH Terms

Conditions

Dyspareunia

Interventions

Estradiolsegesterone acetate and ethinyl estradiol vaginal system

Condition Hierarchy (Ancestors)

Genital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesGenital Diseases, MaleSexual Dysfunction, PhysiologicalMale Urogenital DiseasesSexual Dysfunctions, PsychologicalMental Disorders

Intervention Hierarchy (Ancestors)

EstrenesEstranesSteroidsFused-Ring CompoundsPolycyclic CompoundsEstradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

Title
Dr. Katherine A. Guthrie
Organization
Fred Hutchinson Cancer Research Center
kguthrie@fredhutch.org
2066675595

Study Officials

  • Katherine A Guthrie, PhD

    Fred Hutchinson Cancer 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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

August 3, 2015

First Posted

August 5, 2015

Study Start

April 1, 2016

Primary Completion

May 1, 2017

Study Completion

July 1, 2017

Last Updated

July 12, 2018

Results First Posted

July 12, 2018

Record last verified: 2018-06

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP, ICF

Locations

US(2)