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Accelerated Genital Tract Aging in HIV: Estradiol Clinical Trial

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ClinicalTrials.gov Identifier: NCT04079218
Recruitment Status : Not yet recruiting
First Posted : September 5, 2019
Last Update Posted : September 5, 2019
Sponsor:
Collaborators:
National Institute on Aging (NIA)
Novo Nordisk A/S
Information provided by (Responsible Party):
Kerry Murphy, Albert Einstein College of Medicine

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.

Condition or disease Intervention/treatment Phase
HIV Infection Vaginal Atrophy Menopause Menopause Related Conditions Aging Premature Aging Atrophic Vaginitis Dysbiosis Vaginitis Drug: Estradiol Vaginal Insert Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomly assigned to receive treatment with estradiol vaginal tablets or no treatment.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : September 1, 2019
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : August 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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



Primary Outcome Measures :
  1. 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

  2. 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)


Secondary Outcome Measures :
  1. Vaginal Microbiome [ Time Frame: Between baseline and 6 and 12 weeks ]
    Changes in relative abundance and quantities of bacterial vaginosis associated species

  2. Vaginal cytokines and chemokines [ Time Frame: Between baseline and 6 and 12 weeks ]
    Changes in concentrations of cytokines and chemokines in cervicovaginal lavage (CVL)

  3. 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

  4. HIV-1 RNA levels in the genital tract [ Time Frame: Baseline and 6 and 12 weeks ]
    HIV-1 RNA testing from cervicovaginal lavage fluid



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  • Endometrial hyperplasia or polyps
  • Current unexplained abnormal genital bleeding
  • Current or suspected pregnancy
  • Known current or past thromboembolic disease (deep vein thrombosis or pulmonary embolism, not including thrombophlebitis), myocardial infarction or stroke
  • Known blood clotting disorders including Protein C, Protein S and antithrombin deficiency, Factor V Leiden or prothrombin mutations
  • Hysterectomy
  • Known severe liver disease
  • Use of hormones in the 3 months prior to study enrollment
  • Use of any vaginal or vulvar preparations 1 month prior to enrollment
  • Antibiotic use in the past 30 days
  • Abnormal Pap test in the past year
  • Current acute vaginal infection (diagnosed by wet mount at Visit 1 or 2)
  • History of adverse reaction to vaginal estradiol
  • Any serious disease or chronic condition that might interfere with study compliance
  • Unwilling to agree to the provisions of the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04079218


Contacts
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Contact: Kerry J Murphy, MD 718-839-7885 kerry.murphy@einstein.yu.edu
Contact: Marla J Keller, MD 718-430-3240 marla.keller@einstein.yu.edu

Locations
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United States, New York
Albert Einstein College of Medicine Not yet recruiting
Bronx, New York, United States, 10461
Contact: Kerry J Murphy, MD    718-839-7885    kerry.murphy@einstein.yu.edu   
Contact: Marla J Keller, MD    718-430-3240    marla.keller@einstein.yu.edu   
Sponsors and Collaborators
Albert Einstein College of Medicine
National Institute on Aging (NIA)
Novo Nordisk A/S
Investigators
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Principal Investigator: Kerry J Murphy, MD Albert Einstein College of Medicine

Publications:

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Responsible Party: Kerry Murphy, Assistant Professor, Department of Medicine (Infectious Diseases), Albert Einstein College of Medicine
ClinicalTrials.gov Identifier: NCT04079218     History of Changes
Other Study ID Numbers: 2019-10529
First Posted: September 5, 2019    Key Record Dates
Last Update Posted: September 5, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After publication of the main study findings, external investigators may contact the Principal Investigator Dr. Kerry Murphy for de-identified datasets.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Within 12 months after publication
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.

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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
Keywords provided by Kerry Murphy, Albert Einstein College of Medicine:
HIV Infection
Vaginal Atrophy
Menopause
Vaginal Microbiome
Microbiome
Dysbiosis
Aging
Premature Aging
Atrophic Vaginitis
Additional relevant MeSH terms:
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HIV Infections
Vaginitis
Atrophic Vaginitis
Atrophy
Dysbiosis
Aging, Premature
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Pathological Conditions, Anatomical
Vaginal Diseases
Genital Diseases, Female
Pathologic Processes
Signs and Symptoms
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol
Polyestradiol phosphate
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female