Accelerated Genital Tract Aging in HIV: Estradiol Clinical Trial

Aging Clinical Trial

Official title:

The Impact of HIV on Accelerated Aging in the Female Genital Tract: a Pilot Trial of Topical Estradiol to Improve the Vaginal Microbiome and Symptoms of Vaginal Atrophy in Menopausal Women With HIV

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04079218
• Other study ID #: 2019-10529
• Secondary ID: 1K23AG062400-01A
• Status: Completed
• Phase: Phase 4
• Start date: September 1, 2020
• Est. completion date: August 9, 2023

Study information

• Verified date: February 2024
• Source: Albert Einstein College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: August 9, 2023
• Est. primary completion date: August 9, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Aging
• Aging, Premature
• Atrophic Vaginitis
• Atrophy
• Dysbiosis
• HIV Infection
• HIV Infections
• Menopause
• Menopause Related Conditions
• Premature Aging
• Vaginal Atrophy
• Vaginitis

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Albert Einstein College of Medicine	Bronx	New York

Sponsors (3)

Lead Sponsor	Collaborator
Albert Einstein College of Medicine	National Institute on Aging (NIA), Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Sci Rep. 2016 Nov 29;6:34119. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vaginal Atrophy Symptoms	Change in clinical symptoms measured by most bothersome symptom (MBS) of vaginal atrophy after estradiol treatment	Between baseline and 6 and 12 weeks
Primary	Vaginal Microbiome	Changes in the vaginal microbiome, specifically the relative abundance of protective lactobacillus species L. crispatus as measured by lllumina sequencing and quantities of protective lactobacilli species (L. crispatus, L. jensenii and L. gasseri) as measured by quantitative PCR (qPCR)	Between baseline and 6 and 12 weeks
Secondary	Vaginal Microbiome	Changes in relative abundance and quantities of bacterial vaginosis associated species	Between baseline and 6 and 12 weeks
Secondary	Vaginal cytokines and chemokines	Changes in concentrations of cytokines and chemokines in cervicovaginal lavage (CVL)	Between baseline and 6 and 12 weeks
Secondary	Immunoglobulin (Ig)A and IgG coated bacteria	Differences in levels of live IgA+IgG+ coated, live IgA+IgG- coated, live IgA-IgG-coated and dead bacteria	Baseline and 6 and 12 weeks
Secondary	HIV-1 RNA levels in the genital tract	HIV-1 RNA testing from cervicovaginal lavage fluid	Baseline and 6 and 12 weeks