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.
Brief Title
Accelerated Genital Tract Aging in HIV: Estradiol Clinical Trial
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
HIV Infection
Vaginal Atrophy
Menopause
Menopause Related Conditions
Aging
Premature Aging
Atrophic Vaginitis
Dysbiosis
Vaginitis
Eligibility 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
* 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
* 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
Inclusion 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
* 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
Gender
Female
Gender Based
false
Keywords
HIV Infection
Vaginal Atrophy
Menopause
Vaginal Microbiome
Microbiome
Dysbiosis
Aging
Premature Aging
Atrophic Vaginitis
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
70 Years
Minimum Age
45 Years
NCT Id
NCT04079218
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2019-10529
Overall Status
Completed
Phases
Phase 4
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Change in Most Bothersome Symptom (MBS) of Vaginal Atrophy
Outcome Time Frame
Between baseline (Visit 2) and 12 weeks (Visit 5)
Outcome Description
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.
Outcome Measure
Vaginal Microbiome - Relative Abundance of Lactobacillus Crispatus (L. Crispatus)
Outcome Time Frame
Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Outcome Description
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.
Outcome Measure
Vaginal Microbiome - Quantitative Determination of Protective Lactobacilli Species
Outcome Time Frame
Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Secondary Ids
Secondary Id
1K23AG062400-01A1
Secondary Outcomes
Outcome Description
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)
Outcome Time Frame
Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Outcome Measure
Vaginal Microbiome - Relative Abundance of Bacterial Vaginosis Associated Species
Outcome Description
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.
Outcome Time Frame
Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Outcome Measure
Vaginal Microbiome - Quantitative Determination of Bacterial Vaginosis Associated Species
Outcome Description
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.
Outcome Time Frame
Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
Outcome Measure
Change in Vaginal Cytokine and Chemokine Concentrations
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
70
Minimum Age Number (converted to Years and rounded down)
45
Investigators
Investigator Type
Principal Investigator
Investigator Name
Kerry Murphy
Investigator Email
kerry.murphy@einsteinmed.edu