Accelerated Genital Tract Aging in HIV: Estradiol Clinical Trial

Kerry Murphy

Status and phase: Completed; Phase 4

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

Treatments: Drug: Estradiol Vaginal Insert

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT04079218

1K23AG062400-01A1 (U.S. NIH Grant/Contract)

2019-10529

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: Female

Ages: 45 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Estradiol Vaginal Insert

Experimental group

Description:

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.

Treatment:

Drug: Estradiol Vaginal Insert

No treatment

No Intervention group

Description:

No intervention