Accelerated Genital Tract Aging in HIV: Estradiol Clinical Trial

February 26, 2025 updated by: Kerry Murphy

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Most Bothersome Symptom (MBS) of Vaginal Atrophy
Time Frame: 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 asked to identify and assess the severity of their MBS. The degree of severity of the MBS reported at baseline was then compared to the severity of the MBS reported at 12 weeks and categorically summarized and reported as either "Severity Increased" "Severity Decreased" or "No change in Severity" for the given MBS. Participants whose MBS reported at baseline changed during the follow-up visit at 12 weeks were excluded from the analysis. Participants who did not report an MBS during the baseline visit were also excluded. Data for each possible type of MBS is summarized by study arm.
Between baseline (Visit 2) and 12 weeks (Visit 5)
Vaginal Microbiome - Relative Abundance of Lactobacillus Crispatus (L. Crispatus)
Time Frame: 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 between baseline (visit 2) and 12 weeks (visit 5) will be summarized by study arm.
Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Vaginal Microbiome - Quantitative Determination of Protective Lactobacilli Species
Time Frame: 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 statistics.
Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Vaginal Microbiome - Relative Abundance of Bacterial Vaginosis Associated Species
Time Frame: Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
The relative abundance of bacterial vaginosis (BV) associated bacterial species as quantified by lllumina MiSeq sequencing, will be calculated by dividing the total number of the individual BV-associated species sequences 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 between baseline (visit 2) and 12 weeks (visit 5) will be summarized by study arm for the 3 most common BV-associated species; Gardnerella vaginalis (G. vaginalis); Fannyhessea vaginae (F. vaginae); and Prevotella bivia (P. bivia)
Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Vaginal Microbiome - Quantitative Determination of Bacterial Vaginosis Associated Species
Time Frame: Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Changes in quantities of BV-associated species as measured by quantitative PCR (qPCR) will be determined. BV-associated species will be detected and quantified in colony forming units per milliliter of sample (CFU/mL). Changes in abundance from baseline for each detected species will be summarized by study arm using basic descriptive statistics.
Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Change in Vaginal Cytokine and Chemokine Concentrations
Time Frame: Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Change in concentrations from baseline of vaginal cytokines and chemokines in cervicovaginal lavage (CVL) was determined. Following assay, concentrations for the following cytokines and chemokines, as individually expressed, were reported in picograms per milliliter (pg/mL): IL-1A, Interleukin-8 (IL8); Interferon-gamma inducible protein 10 (IP-10); Monocyte Chemoattractant Protein-1 (MCP-1); and Secretory Leukocyte Protease Inhibitor (SLPI). Change in concentrations for the respective cytokines and chemokines from baseline are summarized by study arm using basic descriptive statistics.
Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
HIV-1 RNA Levels in the Genital Tract
Time Frame: Baseline and 6 and 12 weeks

HIV-1 RNA testing from cervicovaginal lavage fluid will be used to assess HIV-1 concentrations in the genital tract. Concentrations will be summarized by study arm and subsequently analyzed by multivariate linear regression.

Cervicovaginal lavage (CVL) fluid was collected for other measures however due to insufficient funding, CVL HIV-1 viral loads were not run at any time point therefore the data is not available, nor will it be available in the future.
Baseline and 6 and 12 weeks
Immunoglobulin (Ig)A and IgG Coated Bacteria
Time Frame: Baseline and 6 and 12 weeks

Relative differences in levels of live IgA+IgG+ coated, live IgA+IgG- coated, live IgA-IgG-coated and dead bacteria will be summarized using basic descriptive statistics and subsequently analyzed by multivariate linear regression.

Vaginal swabs were collected for quantification of subsets of IgA and IgG coated bacteria however due to insufficient funding, sequencing of these samples has not been performed and therefore data is not available. If we are able to secure additional funding, the sequencing may be performed in the future.
Baseline and 6 and 12 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kerry Murphy

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novo Nordisk A/S
National Institute on Aging (NIA)
Irma L and Abram S Croll Charitable Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 9, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 9, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 3, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 6, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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