Accelerated Genital Tract Aging in HIV: Estradiol Clinical Trial

Phase 4

Completed

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

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.

Recruitment & 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

Arm && Interventions

Group	Intervention	Description
Estradiol Vaginal Insert	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.

Primary Outcome Measures

Name	Time	Method
Vaginal Microbiome	Between baseline and 6 and 12 weeks	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)
Vaginal Atrophy Symptoms	Between baseline and 6 and 12 weeks	Change in clinical symptoms measured by most bothersome symptom (MBS) of vaginal atrophy after estradiol treatment

Secondary Outcome Measures

Name	Time	Method
HIV-1 RNA levels in the genital tract	Baseline and 6 and 12 weeks	HIV-1 RNA testing from cervicovaginal lavage fluid
Vaginal Microbiome	Between baseline and 6 and 12 weeks	Changes in relative abundance and quantities of bacterial vaginosis associated species
Vaginal cytokines and chemokines	Between baseline and 6 and 12 weeks	Changes in concentrations of cytokines and chemokines in cervicovaginal lavage (CVL)
Immunoglobulin (Ig)A and IgG coated bacteria	Baseline and 6 and 12 weeks	Differences in levels of live IgA+IgG+ coated, live IgA+IgG- coated, live IgA-IgG-coated and dead bacteria

Locations (1): Albert Einstein College of Medicine
🇺🇸
Bronx, New York, United States