Accelerated Genital Tract Aging in HIV: Estradiol Clinical Trial

February 1, 2024 updated by: Albert Einstein College of Medicine

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • New York
      • Bronx, New York, United States, 10461
        • Albert Einstein College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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.
Other Names:
  • Vagifem®
  • Vagifem (estradiol vaginal tablet)
No Intervention: No treatment
No intervention

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vaginal Microbiome
Time Frame: Between baseline and 6 and 12 weeks
Changes in relative abundance and quantities of bacterial vaginosis associated species
Between baseline and 6 and 12 weeks
Vaginal cytokines and chemokines
Time Frame: Between baseline and 6 and 12 weeks
Changes in concentrations of cytokines and chemokines in cervicovaginal lavage (CVL)
Between baseline and 6 and 12 weeks
Immunoglobulin (Ig)A and IgG coated bacteria
Time Frame: 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
Baseline and 6 and 12 weeks
HIV-1 RNA levels in the genital tract
Time Frame: Baseline and 6 and 12 weeks
HIV-1 RNA testing from cervicovaginal lavage fluid
Baseline and 6 and 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Albert Einstein College of Medicine

Collaborators

Novo Nordisk A/S
National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Kerry J Murphy, MD, Albert Einstein College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2020

Primary Completion (Actual)

August 9, 2023

Study Completion (Actual)

August 9, 2023

Study Registration Dates

First Submitted

September 3, 2019

First Submitted That Met QC Criteria

September 3, 2019

First Posted (Actual)

September 6, 2019

Study Record Updates

Last Update Posted (Actual)

February 2, 2024

Last Update Submitted That Met QC Criteria

February 1, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-10529
  • 1K23AG062400-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After publication of the main study findings, external investigators may contact the Principal Investigator Dr. Kerry Murphy for de-identified datasets.

IPD Sharing Time Frame

Within 12 months after publication

IPD Sharing Access Criteria

De-identified electronic datasets of published results will be made available to external investigators in a format in which subsequent statistical analyses can be performed.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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