Accelerated Genital Tract Aging in HIV: Estradiol Clinical Trial

What this trial studies

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.

Conditions in scope

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

Interventions

• Estradiol Vaginal Insert (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.

Who can join

Women only · Ages 45 Years to 70 Years · 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

Eligibility wording paraphrased from the public record. View the full criteria on ClinicalTrials.gov before contacting a site.

Where it’s happening

Status & timeline

• Overall status: Completed
• Study type: Interventional
• Phase: PHASE4
• Start date: 2020-09-01
• Primary completion: 2023-08-09
• Last update posted: 2025-03-14
• First posted: 2019-09-06

Sponsor & contact

Lead sponsor: Kerry Murphy (Other)

Collaborators: National Institute on Aging (NIA), Novo Nordisk A/S, Irma L and Abram S Croll Charitable Trust

For trial site contact information, use the official record at ClinicalTrials.gov. Contact details change frequently and the public record is the source of truth.

Outcome measures

Primary outcomes

• Change in Most Bothersome Symptom (MBS) of Vaginal Atrophy (Between baseline (Visit 2) and 12 weeks (Visit 5))
  Change in the severity of MBS of vaginal atrophy as reported during the baseline visit was assessed at 12 weeks (Visit 5). During the baseline visit, participants were asked to identify their MBS and assess the severity of the MBS on an ordinal scale of "None," "Mild," "Moderate," or "Severe." During the follow-up visit at 12 weeks participants were again…
• Vaginal Microbiome - Relative Abundance of Lactobacillus Crispatus (L. Crispatus) (Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5))
  The relative abundance of the protective Lactobacillus species, L. crispatus, as quantified by lllumina MiSeq sequencing will be calculated by dividing the total number of L crispatus sequences detected in a sample by the total number of sequences from all bacterial species detected in the same sample. This proportion will be expressed as a percentage. The change in relative abundance…
• Vaginal Microbiome - Quantitative Determination of Protective Lactobacilli Species (Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5))
  Changes in the vaginal microbiome, specifically the quantities of protective Lactobacilli species (L. crispatus, L. jensenii and L. gasseri) as measured by quantitative PCR (qPCR) will be determined. The three Lactobacilli species will be identified and quantified in colony forming units per milliliter of sample (CFU/mL). Changes in abundance from baseline will be summarized by study arm using basic descriptive…

Related ClearedRx care

If you’re reading this trial because you have menopause symptoms now, you don’t have to wait for a trial to access evidence-based care. ClearedRx prescribes the same FDA-approved and compounded HRT products that have been studied in trials like this one for decades.