Accelerated Genital Tract Aging in HIV: Estradiol Clinical Trial

NCT ID: NCT04079218

Last Updated: 2025-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2023-08-09

Brief Summary

During menopause, there is a decrease in a hormone estrogen, which leads to aging of the vagina. Vaginal aging includes changes in the type and amount of healthy bacteria in the vagina, inflammation and a breakdown of natural barriers that keep the vagina healthy and protected from infections. Some menopausal women develop a condition called vaginal atrophy, which causes vaginal dryness, irritation, pain with sex, and itching. We are testing whether an estradiol tablet placed inside the vagina will lead to fewer changes in the types of bacteria present in the vagina, improve vaginal atrophy symptoms and ultimately keep the vagina healthier for a longer. This is important for women with HIV as they are living longer, healthier, sexually active lives due to successful treatment with antiretrovirals.

Detailed Description

HIV may be associated with premature aging in the female genital tract including alterations in the vaginal microbiome and mucosal inflammation, which may increase risk for vaginal atrophy, urinary tract infections (UTI) and other genital tract infections. This study will determine whether use of vaginal estradiol for 12 weeks in menopausal women living with HIV with symptomatic vaginal atrophy will improve atrophy symptoms and the vaginal microbiome and reduce mucosal inflammation thereby improving vaginal health. This study will include 50 participants randomized to treatment with a vaginal estradiol insert or no therapy for 12 weeks and will have 4 study visits.

Conditions

HIV Infection; Vaginal Atrophy; Menopause; Menopause Related Conditions; Aging; Premature Aging; Atrophic Vaginitis; Dysbiosis; Vaginitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Estradiol Vaginal Insert

Using a pre-loaded single-use plastic applicator, participants will insert one 10 microgram estradiol tablet intravaginally daily for 2 weeks and then one tablet twice weekly for the remainder of the study for a total of 12 weeks.

Group Type: EXPERIMENTAL

Estradiol Vaginal Insert

Intervention Type: DRUG

Using a pre-loaded single-use plastic applicator, participants will insert one 10 microgram estradiol tablet intravaginally daily for 2 weeks and then one tablet twice weekly for the remainder of the study for a total of 12 weeks.

No treatment

No intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Estradiol Vaginal Insert

Using a pre-loaded single-use plastic applicator, participants will insert one 10 microgram estradiol tablet intravaginally daily for 2 weeks and then one tablet twice weekly for the remainder of the study for a total of 12 weeks.

Intervention Type: DRUG

Other Intervention Names

Vagifem®; Vagifem (estradiol vaginal tablet)

Eligibility Criteria

Inclusion Criteria

• HIV infection
• Females aged 45-70
• Menopause defined by having no menstrual periods for 12 consecutive months, confirmed with serum follicle-stimulating hormone (FSH) level >40 IU/ml and serum estradiol level <20 pg/ml
• Symptomatic vaginal atrophy defined as reporting at least once per week in the past 30 days, 1 or more of the following symptoms of moderate or severe intensity: Dryness, Itching, Irritation, Soreness or pain OR Pain associated with sexual activity at least once
• Evidence of atrophy on exam, including thin, pale and dry vaginal and vulvar surfaces
• Agrees not to use vaginal products other than vaginal estradiol tablet during the clinical trial

Exclusion Criteria

• Current or previous history of breast cancer or estrogen dependent neoplasia
• Current or past thromboembolic disease (deep vein thrombosis or pulmonary embolism, not including thrombophlebitis)
• Current or previous history of myocardial infarction or stroke
• Known blood clotting disorders including Protein C, Protein S and antithrombin deficiency, Factor V Leiden or prothrombin mutations
• Known severe liver disease including cirrhosis or active Hepatitis B
• History of adverse reaction to vaginal estradiol
• Current unexplained or unevaluated abnormal genital bleeding
• Current or suspected pregnancy
• If < age 55, had a hysterectomy and has at least one ovary
• Pelvic or vaginal surgery in the prior 60 days
• Use of systemic reproductive hormones in the past 2 months
• Antibiotic use in the past 30 days
• Use of immunosuppressive medications in the prior 60 days including biologics, chemotherapeutics or post-transplant immunosuppressive medications
• Use of any vaginal or vulvar preparations 1 month prior to enrollment
• Current active vaginal infection (diagnosed by wet mount at Visit 1 or 2)
• Any serious disease or chronic condition that might interfere with study compliance
• Unwilling to agree to the provisions of the protocol

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

Irma L and Abram S Croll Charitable Trust

UNKNOWN

Sponsor Role: collaborator

Kerry Murphy

OTHER

Sponsor Role: lead

Responsible Party

Kerry Murphy

Assistant Professor, Department of Medicine (Infectious Diseases)

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kerry J Murphy, MD

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein College of Medicine

Locations

Albert Einstein College of Medicine

The Bronx, New York, United States

Countries

United States

References

Murphy K, Keller MJ, Anastos K, Sinclair S, Devlin JC, Shi Q, Hoover DR, Starkman B, McGillick J, Mullis C, Minkoff H, Dominguez-Bello MG, Herold BC. Impact of reproductive aging on the vaginal microbiome and soluble immune mediators in women living with and at-risk for HIV infection. PLoS One. 2019 Apr 26;14(4):e0216049. doi: 10.1371/journal.pone.0216049. eCollection 2019.

Reference Type: BACKGROUND

PMID: 31026271 (View on PubMed)

Shen J, Song N, Williams CJ, Brown CJ, Yan Z, Xu C, Forney LJ. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis. Sci Rep. 2016 Apr 22;6:24380. doi: 10.1038/srep24380.

Reference Type: BACKGROUND

PMID: 27103314 (View on PubMed)

Hummelen R, Macklaim JM, Bisanz JE, Hammond JA, McMillan A, Vongsa R, Koenig D, Gloor GB, Reid G. Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. PLoS One. 2011;6(11):e26602. doi: 10.1371/journal.pone.0026602. Epub 2011 Nov 2.

Reference Type: BACKGROUND

PMID: 22073175 (View on PubMed)

Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, Viscidi RP, Burke AE, Ravel J, Gravitt PE. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause. 2018 Nov;25(11):1321-1330. doi: 10.1097/GME.0000000000001236.

Reference Type: BACKGROUND

PMID: 30358729 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29554173 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1K23AG062400-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2019-10529

Identifier Type: -

Identifier Source: org_study_id