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| ID | Type | Description | Link |
|---|---|---|---|
| 1K23AG062400-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
| Novo Nordisk A/S | INDUSTRY |
| Irma L and Abram S Croll Charitable Trust | UNKNOWN |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Estradiol Vaginal Insert | Experimental | 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. |
|
| No treatment | No Intervention | No intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Most Bothersome Symptom (MBS) of Vaginal Atrophy | 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) | 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 | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Vaginal Microbiome - Relative Abundance of Bacterial Vaginosis Associated Species | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| HIV-1 RNA Levels in the Genital Tract | 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kerry J Murphy, MD | Albert Einstein College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Albert Einstein College of Medicine | The Bronx | New York | 10461 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31026271 | Background | Murphy K, Keller MJ, Anastos K, Sinclair S, Devlin JC, Shi Q, Hoover DR, Starkman B, McGillick J, Mullis C, Minkoff H, Dominguez-Bello MG, Herold BC. Impact of reproductive aging on the vaginal microbiome and soluble immune mediators in women living with and at-risk for HIV infection. PLoS One. 2019 Apr 26;14(4):e0216049. doi: 10.1371/journal.pone.0216049. eCollection 2019. | |
| 27103314 | Background | Shen J, Song N, Williams CJ, Brown CJ, Yan Z, Xu C, Forney LJ. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis. Sci Rep. 2016 Apr 22;6:24380. doi: 10.1038/srep24380. |
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After publication of the main study findings, external investigators may contact the Principal Investigator Dr. Kerry Murphy for de-identified datasets.
Within 12 months after publication
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.
Not provided
60 participants were consented and randomized into the study. Of these, 51 completed the trial. One participant in the non treatment arm and 8 participants in the estradiol arm did not complete the study. An additional 19 participants were screened but deemed ineligible for the study and not randomized. There were no HIV negative participants in the trial. Study documents refer to two related but separate studies: a trial for HIV+ participants and another study which includes HIV- participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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. |
| FG001 | No Treatment | No intervention |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Most Bothersome Symptom (MBS) of Vaginal Atrophy | 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. | Participants whose MBS reported at baseline changed during the follow-up visit at 12 weeks and participants who did not report a MBS during the baseline visit were excluded. The overall number of participants analyzed has been updated to reflect this. | Posted | Count of Participants | Participants | Between baseline (Visit 2) and 12 weeks (Visit 5) |
Up to 13 weeks following randomization
The Division of AIDS (DAIDS) Female Genital Grading Table for Use in Microbicide Studies will be the primary tool for grading adverse events (https://rsc.niaid.nih.gov/sites/default/files/addendum-1-female-genitalgrading-table-v1-nov-2007.pdf.)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoglycemia | Metabolism and nutrition disorders | Non-systematic Assessment | Verbatim Term: Blood Sugar dropped. Patient was hospitalized. Grade 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pigmentation loss | Reproductive system and breast disorders | Non-systematic Assessment | Verbatim Term. Pigmentation loss of bilateral internal labia/complete vulvar area. Grade 3 |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kerry Murphy | Albert Einstein College of Medicine | 718-839-7885 | kerry.murphy@einsteinmed.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 9, 2021 | Dec 19, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 14, 2023 | Dec 19, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D019588 | Aging, Premature |
| D059268 | Atrophic Vaginitis |
| D064806 | Dysbiosis |
| D014627 | Vaginitis |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| D004958 | Estradiol |
| ID | Term |
|---|---|
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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Participants will be randomly assigned to receive treatment with estradiol vaginal tablets or no treatment.
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|
| Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5) |
| Vaginal Microbiome - Quantitative Determination of Bacterial Vaginosis Associated Species | 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 | 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) |
| Baseline and 6 and 12 weeks |
| Immunoglobulin (Ig)A and IgG Coated Bacteria | 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 |
| 22073175 | Background | Hummelen R, Macklaim JM, Bisanz JE, Hammond JA, McMillan A, Vongsa R, Koenig D, Gloor GB, Reid G. Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. PLoS One. 2011;6(11):e26602. doi: 10.1371/journal.pone.0026602. Epub 2011 Nov 2. |
| 30358729 | Background | Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, Viscidi RP, Burke AE, Ravel J, Gravitt PE. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause. 2018 Nov;25(11):1321-1330. doi: 10.1097/GME.0000000000001236. |
| 29554173 | Background | Mitchell CM, Reed SD, Diem S, Larson JC, Newton KM, Ensrud KE, LaCroix AZ, Caan B, Guthrie KA. Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial. JAMA Intern Med. 2018 May 1;178(5):681-690. doi: 10.1001/jamainternmed.2018.0116. |
| Physician Decision |
|
| Lost to Follow-up |
|
| BG001 | No Treatment | No intervention |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Customized age ranges were collected and reported as described in the study protocol. | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Plasma HIV-1 Viral Load | Plasma HIV-1 Viral Load was assessed at baseline as a dichotomous variable. The number of participants who were determined to have "Detectable" vs "Undetectable" HIV-1 load was summarized by study arm. A viral load of <40 copies/ml was defined as undetectable. A viral > or = 40 copies/ml was defined as detectable. | Count of Participants | Participants |
|
| Vaginal Cytokine and Chemokine Concentrations | Concentrations of vaginal cytokines and chemokines in cervicovaginal lavage (CVL) was determined. Upon assay, concentrations for the following cytokines and chemokines as individually expressed was 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). Concentrations are summarized by study arm using basic descriptive statistics. | Mean | Standard Deviation | pg/mL |
|
| Vaginal Symptom Index (VSI) | VSI was assessed at baseline. The VSI is a composite measure, calculated as the mean of 5 vaginal symptoms: dryness, itching, irritation, soreness, dyspareunia. Each symptom was given a score of 0-3 corresponding to either no symptoms, mild, moderate, or severe symptoms. | Mean | Standard Deviation | score on a scale |
|
| Vaginal Microbiome - Detectable Lactobacillus Crispatus (L. Crispatus) | The number/percentage of participants with detectable concentrations of the protective Lactobacillus species, L. crispatus, as quantified by lllumina MiSeq sequencing, is summarized by study arm. | Data was not collected for 3 participants in the 'Estradiol' study arm and 1 participant in the 'No Treatment' study arm at Visit 2 (baseline). | Count of Participants | Participants |
|
| Vaginal Microbiome - Detectable Bacterial Vaginosis-Associated Species | The number/percentage of participants with detectable concentrations of the three most common Bacterial Vaginosis-associated species: Gardnerella vaginalis (G. vaginalis); Fannyhessea vaginae (F. vaginae); and Prevotella bivia (P. bivia), as quantified by lllumina MiSeq sequencing, is summarized by study arm. | Data was not collected for 3 participants in the 'Estradiol' study arm and 1 participant in the 'No Treatment' study arm at Visit 2 (baseline). | Count of Participants | Participants |
|
|
|
|
| Primary | Vaginal Microbiome - Relative Abundance of Lactobacillus Crispatus (L. Crispatus) | 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. | Samples were not available for microbiome studies for 3 participants in the 'Estradiol' study arm and 1 participant in the 'No Treatment' study arm at both Visits 2 & 5 therefore there is no microbiome data available nor will there be in the future for these participants. Vaginal swabs were also collected at 6 weeks for all participants however due to lack of funding, sequencing was not performed therefore the data is not available nor will it be in the future. | Posted | Mean | Standard Deviation | change in percentage of sequences | Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5) |
|
|
|
| Primary | Vaginal Microbiome - Quantitative Determination of Protective Lactobacilli Species | 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. | Though cervicovaginal lavage samples were collected and utilized for other outcome measures reported including cytokine levels, etc, the portion of the cervicovaginal lavage that was collected for qPCR for the quantitative determination of protective Lactobacilli species was not utilized as we did not have sufficient funding to run qPCR. Therefore qPCR was not performed on any sample at any time point. qPCR data is not available nor will it be available in the future. | Posted | Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5) |
|
|
| Secondary | Vaginal Microbiome - Relative Abundance of Bacterial Vaginosis Associated Species | 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) | Samples were not available for microbiome studies for 3 participants in the 'Estradiol' study arm and 1 participant in the 'No Treatment' study arm at both Visits 2 & 5 therefore there is no microbiome data available nor will there be in the future for these participants. Vaginal swabs were also collected at 6 weeks for all participants however due to lack of funding, sequencing was not performed therefore the data is not available nor will it be in the future. | Posted | Mean | Standard Deviation | change in percentage of sequences | Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5) |
|
|
|
| Secondary | Vaginal Microbiome - Quantitative Determination of Bacterial Vaginosis Associated Species | 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. | Though cervicovaginal lavage samples were collected and utilized for other outcome measures reported including cytokine levels, etc, the portion of the cervicovaginal lavage sample collected for qPCR for the quantitative determination of bacterial vaginosis associated species was not utilized as we did not have sufficient funding to run qPCR. Therefore qPCR was not performed on any sample at any time point. qPCR data for these species is not available nor will it be available in the future. | Posted | Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5) |
|
|
| Secondary | Change in Vaginal Cytokine and Chemokine Concentrations | 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. | CVL was collected at 6 weeks however due to insufficient funding, levels of cytokines and chemokines were not run at this time point. Therefore the data is not available nor will it be in the future. | Posted | Mean | Standard Deviation | pg/mL | Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5) |
|
|
|
| Other Pre-specified | HIV-1 RNA Levels in the Genital Tract | 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. | Not Posted | Baseline and 6 and 12 weeks | Participants |
| Other Pre-specified | Immunoglobulin (Ig)A and IgG Coated Bacteria | 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. | Not Posted | Baseline and 6 and 12 weeks | Participants |
| Post-Hoc | Change in Vaginal Symptom Index (VSI) | Change in VSI was determined between Visit 2 and Visit 5. The VSI is a composite measure, calculated as the mean of 5 vaginal symptoms: dryness, itching, irritation, soreness, dyspareunia. Each symptom was given a score of 0-3 corresponding to either no symptoms, mild, moderate, or severe symptoms. | Posted | Mean | Standard Deviation | score on a scale | Between Baseline (Visit 2) and 12 weeks (Visit 5) |
|
|
|
| Post-Hoc | Vaginal Microbiome - Detectable Lactobacillus Crispatus (L. Crispatus) | The number/percentage of participants with detectable concentrations of the protective Lactobacillus species, L. crispatus, as quantified by lllumina MiSeq sequencing, is summarized by study arm. | Data was not collected for 3 participants in the 'Estradiol' study arm and 1 participant in the 'No Treatment' study arm at Visit 5 (12 weeks) therefore data is not and will not be available. Samples were collected at 6 weeks however due to insufficient finding, sequencing was not performed at the 6 week timepoint and therefore is not available and will not be available in the future. | Posted | Count of Participants | Participants | 12 weeks (Visit 5) |
|
|
|
| Post-Hoc | Vaginal Microbiome - Detectable Bacterial Vaginosis-Associated Species | The number/percentage of participants with detectable concentrations of the three most common Bacterial Vaginosis-associated species: Gardnerella vaginalis (G. vaginalis); Fannyhessea vaginae (F. vaginae); and Prevotella bivia (P. bivia), as quantified by lllumina MiSeq sequencing, is summarized by study arm. | Data was not collected for 3 participants in the 'Estradiol' study arm and 1 participant in the 'No Treatment' study arm at Visit 5 (12 weeks) therefore data is not and will not be available. Samples were collected at 6 weeks however due to insufficient finding, sequencing was not performed at the 6 week timepoint and therefore is not available and will not be available in the future. | Posted | Count of Participants | Participants | 12 weeks (Visit 5) |
|
|
|
| Post-Hoc | Change in Vaginal Microbiome - Detectable Lactobacillus Crispatus (L. Crispatus) | Change from baseline in the percentage of participants with detectable concentrations of the protective Lactobacillus species, L. crispatus, as quantified by lllumina MiSeq sequencing, is summarized by study arm. The value was obtained by calculating the percentage difference in participants with a detectable level at baseline (Visit 2) when compared to 12 weeks (Visit 5). | Data was not collected for 3 participants in the 'Estradiol' study arm and 1 participant in the 'No Treatment' study arm at Visit 5 (12 weeks) therefore data is not and will not be available. Samples were collected at 6 weeks however due to insufficient finding, sequencing was not performed at the 6 week timepoint and therefore is not available and will not be available in the future. | Posted | Number | percentage change detectable sequences | Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5) |
|
|
|
| Post-Hoc | Change in Vaginal Microbiome - Detectable Bacterial Vaginosis-Associated Species | Change from baseline in the percentage of participants with detectable concentrations of the three most common Bacterial Vaginosis-associated species: Gardnerella vaginalis (G. vaginalis); Fannyhessea vaginae (F. vaginae); and Prevotella bivia (P. bivia), as quantified by lllumina MiSeq sequencing, is summarized by study arm. Values were obtained for each species by calculating the percentage difference in participants with a detectable level at baseline (Visit 2) when compared to 12 weeks (Visit 5). | Data was not collected for 3 participants in the 'Estradiol' study arm and 1 participant in the 'No Treatment' study arm at Visit 5 (12 weeks) therefore data is not and will not be available. Samples were collected at 6 weeks however due to insufficient finding, sequencing was not performed at the 6 week timepoint and therefore is not available and will not be available in the future. | Posted | Number | percentage change detectable sequences | Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5) |
|
|
|
| 1 |
| 33 |
| 4 |
| 33 |
| 20 |
| 33 |
| EG001 | No Treatment | No intervention | 0 | 27 | 2 | 27 | 10 | 27 |
|
| Myocardial Infarction | Cardiac disorders | Non-systematic Assessment | Secondary to drug use. Determined by autopsy. Patient expired. |
|
| Hospitalization for Gastrointestinal Bleed (GIB) | Gastrointestinal disorders | Non-systematic Assessment | Grade 4 |
|
| Fractured Right Distal Fibula | Injury, poisoning and procedural complications | Non-systematic Assessment | Grade 3 |
|
| Liver Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| Hospitalization for Chest Pain | Cardiac disorders | Non-systematic Assessment | Admit for pulmonary edema and hypertensive emergency in setting of end stage renal disease and known underlying cardiac disease |
|
|
| Hemoglobin Decreased | Blood and lymphatic system disorders | Non-systematic Assessment | Verbatim Term: Hemoglobin levels 9.8 g/dL (chronic anemia), 10.0 g/dL and 10.3 g/dL. All Grade 1 |
|
| Leg weakness | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Groin Pain | Renal and urinary disorders | Non-systematic Assessment | Worsening of chronic condition. Secondary to non-obstructing kidney stone and myomatous uterus. Grade 1 |
|
| Vaginal Discharge | Reproductive system and breast disorders | Non-systematic Assessment | Both Grade 1 |
|
| Urinary Frequency | Renal and urinary disorders | Non-systematic Assessment | Verbatim Term: More frequent urination at night. Grade 1 |
|
| Brown (Vaginal) Discharge | Reproductive system and breast disorders | Non-systematic Assessment | Both Grade 1 |
|
| Vaginal Cramping | Reproductive system and breast disorders | Non-systematic Assessment | Grade 1 |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment | Grade 1 |
|
| Rash maculopapular | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Pruritic rash on left forearm. Grade 1 |
|
| Edema Limbs | General disorders | Non-systematic Assessment | Verbatim Term: Lower extremity edema. Grade 1; Edema to medial/lateral foot after surgery. Grade 2 |
|
| Vulvar Erythema | Reproductive system and breast disorders | Non-systematic Assessment | Bilateral. Grade 2 |
|
| Trichomonas | Infections and infestations | Non-systematic Assessment | Grade 2 |
|
| Yeast Infection | Infections and infestations | Non-systematic Assessment | Both Grade 1 |
|
| Healing Biopsy Sites | Injury, poisoning and procedural complications | Non-systematic Assessment | Grade 1 |
|
| Urinary Tract Infection | Infections and infestations | Non-systematic Assessment | Grade 1 |
|
| Back Pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | One Grade 1 and one Grade 2 |
|
| Abdominal Pain | Gastrointestinal disorders | Non-systematic Assessment | Grade 1 |
|
| Bacterial Vaginosis | Infections and infestations | Non-systematic Assessment | Grade 2 |
|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment | Secondary to GIB |
|
| Dark Stools | Gastrointestinal disorders | Non-systematic Assessment | Secondary to GIB |
|
| Hemoglobin decreased 8.7 | Blood and lymphatic system disorders | Non-systematic Assessment | Hemoglobin decreased from 10.1 to 8.7 in setting of heavy nose bleeds, grade 2 |
|
| Epigastric pain | Gastrointestinal disorders | Non-systematic Assessment | ED visit for epigastric pain, symptoms treated and sent home. Grade 2 |
|
| Headache | Nervous system disorders | Non-systematic Assessment | Seen in ED for worsening migraines, treated and sent home from ED. Grade 2 |
|
| Bronchitis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | See in ED for bronchitis symptoms, treated and send home from ED. Grade 2 |
|
| Chest pain | Gastrointestinal disorders | Non-systematic Assessment | Seen in ED for chest pain, attributed to acid reflux, treated and send home from ED. Grade 2 |
|
| Diarrhea and abdominal cramping | Gastrointestinal disorders | Non-systematic Assessment | In setting of new medications including metformin and jardiance as well as a viral illness. Grade 2 |
|
| Tooth extraction | Surgical and medical procedures | Non-systematic Assessment | Tooth extraction under local anesthesia, grade 1 |
|
| Sinus infection | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Sinus infection treated with antibiotics. Grade 1 |
|
| COPD exacerbation | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Seen in ED for COPD exacerbation, treated and send home from ED. Grade 2; Hospitalized for COPD exacerbation. Grade 3 |
|
Not provided
Not provided
Not provided
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D014623 | Vaginal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D010335 | Pathologic Processes |
| D011083 |
| Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Severity Decreased |
|
| No change in Severity |
|
| Severity Decreased |
|
| No change in Severity |
|
| Severity Decreased |
|
| No change in Severity |
|
| Severity Decreased |
|
| No change in Severity |
|
| P. bivia |
|
| IP-10 |
|
| MCP-1 |
|
| SLPI |
|
| P. bivia |
|
| P. bivia |
|