A Phase 4 interventional study of Estradiol Vaginal Insert in HIV Infection, Vaginal Atrophy and Menopause, sponsored by Kerry Murphy. Completed at 1 site in United States. Open to female participants aged 45 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-03-14.
Sponsored by Kerry Murphy · Phase 4, Interventional, and Treatment
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.
4,734 studies on the registry are indexed under HIV Infections; 244 are open to participants now.
This study's enrollment of 60 is below the median of 80 across 3,489 interventional studies indexed under HIV Infections.
Browse HIV Infections studies →This is the only study on the registry with Kerry Murphy as lead sponsor.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
No intervention
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.
Also known as: Vagifem®, Vagifem (estradiol vaginal tablet)
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.
Time frame: 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.
Time frame: 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.
Time frame: Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
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)
Time frame: 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.
Time frame: 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.
Time frame: Between baseline (Visit 2) and 6 weeks and 12 weeks (Visit 5)
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.
Time frame: 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.
Time frame: Baseline and 6 and 12 weeks
| Milestone | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| Started | 33 | 27 |
| Completed | 25 | 26 |
| Not completed | 8 | 1 |
| Withdrew: Death | 1 | 0 |
| Withdrew: Withdrawal by subject | 3 | 0 |
| Withdrew: Physician decision | 4 | 0 |
| Withdrew: Lost to follow-up | 0 | 1 |
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 | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| Itching — Severity Increased | 0 | 1 |
| Itching — Severity Decreased | 8 | 4 |
| Itching — No change in Severity | 0 | 1 |
| Dryness — Severity Increased | 0 | 1 |
| Dryness — Severity Decreased | 9 | 3 |
| Dryness — No change in Severity | 1 | 6 |
| Soreness — Severity Increased | 0 | 0 |
| Soreness — Severity Decreased | 1 | 0 |
| Soreness — No change in Severity | 0 | 0 |
| Irritation — Severity Increased | 0 | 0 |
| Irritation — Severity Decreased | 0 | 0 |
| Irritation — No change in Severity | 0 | 0 |
| Dyspareunia — Severity Increased | 0 | 0 |
| Dyspareunia — Severity Decreased | 2 | 0 |
| Dyspareunia — No change in Severity | 0 | 0 |
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.
| change in percentage of sequences | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| Vaginal Microbiome - Relative Abundance of Lactobacillus Crispatus (L. Crispatus) | -1.37 ± 4.25 | -6.9 ± 25.14 |
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.
No measurements were reported for this outcome.
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)
| change in percentage of sequences | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| G. vaginalis | 3.15 ± 27.69 | -1.22 ± 17.03 |
| F. vaginae | -5.17 ± 7.49 | -1.14 ± 8.72 |
| P. bivia | -0.82 ± 1.79 | -1.09 ± 2.75 |
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.
No measurements were reported for this outcome.
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.
| pg/mL | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| IL-1A | 0.17 ± 0.53 | -0.07 ± 0.14 |
| IL-8 | -0.07 ± 0.28 | 0.11 ± 0.07 |
| IP-10 | -0.04 ± 0.23 | 0.02 ± 0.06 |
| MCP-1 | -0.13 ± 0.02 | 0.04 ± 0.21 |
| SLPI | 0.18 ± 0.03 | -0.07 ± 0.00 |
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.
Results for this outcome have not been posted.
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.
Results for this outcome have not been posted.
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.
| score on a scale | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| Change in Vaginal Symptom Index (VSI) | -1.01 ± 0.65 | -0.38 ± 0.62 |
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.
| Participants | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| Vaginal Microbiome - Detectable Lactobacillus Crispatus (L. Crispatus) | 3 | 5 |
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.
| Participants | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| G. vaginalis | 11 | 16 |
| F. vaginae | 11 | 11 |
| P. bivia | 8 | 9 |
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).
| percentage change detectable sequences | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| Change in Vaginal Microbiome - Detectable Lactobacillus Crispatus (L. Crispatus) | -9.1 | -8.0 |
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).
| percentage change detectable sequences | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| G. vaginalis | -13.6 | 8.0 |
| F. vaginae | 0 | -4.0 |
| P. bivia | -13.6 | -24.0 |
Collected over Up to 13 weeks following randomization. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Estradiol Vaginal Insert | 1/33 (3%) | 4/33 (12.1%) | 20/33 (60.6%) |
| No Treatment | 0/27 (0%) | 2/27 (7.4%) | 10/27 (37%) |
| Event | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| HypoglycemiaMetabolism and nutrition disorders | 0/33 | 1/27 |
| Fractured Right Distal FibulaInjury, poisoning and procedural complications | 0/33 | 1/27 |
| Myocardial InfarctionCardiac disorders | 1/33 | 0/27 |
| Hospitalization for Gastrointestinal Bleed (GIB)Gastrointestinal disorders | 1/33 | 0/27 |
| Liver CancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/33 | 0/27 |
| Hospitalization for Chest PainCardiac disorders | 1/33 | 0/27 |
| Event | Estradiol Vaginal Insert | No Treatment |
|---|---|---|
| Back PainMusculoskeletal and connective tissue disorders | 3/33 | 0/27 |
| Hemoglobin DecreasedBlood and lymphatic system disorders | 1/33 | 2/27 |
| Brown (Vaginal) DischargeReproductive system and breast disorders | 2/33 | 0/27 |
| COPD exacerbationRespiratory, thoracic and mediastinal disorders | 2/33 | 0/27 |
| Vaginal DischargeReproductive system and breast disorders | 1/33 | 1/27 |
| Edema LimbsGeneral disorders | 1/33 | 1/27 |
| Vulvar ErythemaReproductive system and breast disorders | 0/33 | 1/27 |
| TrichomonasInfections and infestations | 1/33 | 1/27 |
| Yeast InfectionInfections and infestations | 1/33 | 1/27 |
| Bacterial VaginosisInfections and infestations | 1/33 | 1/27 |
| Age, Continuous(years) | Estradiol Vaginal Insert | No Treatment | Total |
|---|---|---|---|
| Mean | 59.3 ± 4.66 | 59.5 ± 4.92 | 59.4 ± 4.75 |
| Age, Customized(Participants) | Estradiol Vaginal Insert | No Treatment | Total |
|---|---|---|---|
| 45-55 years old | 4 | 6 | 10 |
| 56-70 years old | 21 | 20 | 41 |
| Sex: Female, Male(Participants) | Estradiol Vaginal Insert | No Treatment | Total |
|---|---|---|---|
| Female | 25 | 26 | 51 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Estradiol Vaginal Insert | No Treatment | Total |
|---|---|---|---|
| Hispanic or Latino | 5 | 9 | 14 |
| Not Hispanic or Latino | 19 | 17 | 36 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Race (NIH/OMB)(Participants) | Estradiol Vaginal Insert | No Treatment | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 20 | 20 | 40 |
| White | 2 | 2 | 4 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 3 | 6 |
| Region of Enrollment(participants) | Estradiol Vaginal Insert | No Treatment | Total |
|---|---|---|---|
| United States | 25 | 26 | 51 |
| Plasma HIV-1 Viral Load(Participants) | Estradiol Vaginal Insert | No Treatment | Total |
|---|---|---|---|
| Detectable | 5 | 5 | 10 |
| Undetectable | 20 | 21 | 41 |
| Vaginal Cytokine and Chemokine Concentrations(pg/mL) | Estradiol Vaginal Insert | No Treatment | Total |
|---|---|---|---|
| IL-1A | 1.88 ± 0.701 | 1.93 ± 0.669 | 1.91 ± 0.68 |
| IL-8 | 2.58 ± 0.675 | 2.33 ± 1.06 | 2.45 ± 0.89 |
| IP-10 | 2.24 ± 0.740 | 1.96 ± 0.848 | 2.10 ± 0.80 |
| MCP-1 | 1.28 ± 0.753 | 1.12 ± 0.972 | 1.20 ± 0.87 |
| SLPI | 4.42 ± 0.584 | 4.47 ± 0.722 | 4.45 ± 0.65 |
3 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — After publication of the main study findings, external investigators may contact the Principal Investigator Dr. Kerry Murphy for de-identified datasets.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
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 of the drug tested here: Estradiol