Female Urogenital DiseasesPhase 4IMPLORENCT03996603
Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy
A Phase 4 study testing Conjugated Estrogens Cream in people with Female Urogenital Diseases and Vaginal Atrophy, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
In this proposed pilot study, 16S ribosomal RNA (rRNA) gene sequencing will be used in the analysis of bacterial communities (microbiomes) in postmenopausal women with vulvovaginal atrophy (VVA) before and after eight weeks of vaginal estrogen use. Read more about this study
- Who is it for?
- Ages 55 years and older, women only
- Conditions the study is for
- Female Urogenital Diseases, Vaginal Atrophy, Postmenopausal Atrophic Vaginitis
- What is being tested?
- Conjugated Estrogens Cream
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2019to 14 Jan 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal with vulvovaginal atrophy
- Age ≥55 years old and a screening vaginal pH of ≥5.
- Without menses for ≥12 months.
- No uterovaginal or vaginal vault prolapse beyond the hymen.
- No estrogen replacement within the last month (may come off current treatment, i.e. wash out, to join the study)
Who cannot join
- Patients with BMI >35kg/m2
- Any patients with infections requiring antibiotic or antifungal therapy during the study period.
- Study patients may not use any vaginal suppositories, douches, or vaginal hygiene wipes within the month preceding enrollment. For patients already on hormone therapy, will be allowed to undergo a "wash out" period of estrogen or progesterone products for one month prior to enrollment.
- Additional exclusions included patients with systemic conditions requiring immunosuppressive drugs, currently receiving chemotherapy, or history of pelvic radiation.
- Any patients with contraindications to vaginal estrogen therapy including: vaginal bleeding of unknown etiology; known, suspected, or history of breast cancer or estrogen-dependent neoplasia; active DVT, PE, or h/o these conditions; active arterial thromboembolic disease (ie. stroke or MI) or h/o of these; known liver disease or thrombophilic disorders.
- Current tobacco use.
- Allergy to Premarin® or its constituents.
- Concurrent use of steroid creams for other indications (ie. lichen sclerosis)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35233
About this study
Official title: IMPLORE Study: Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy
In this proposed pilot study, 16S ribosomal RNA (rRNA) gene sequencing will be used in the analysis of bacterial communities (microbiomes) in postmenopausal women with vulvovaginal atrophy (VVA) before and after eight weeks of vaginal estrogen use. The investigators plan to characterize the composition and dynamics of the microbiomes of the vagina, bladder, and rectum for quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) before and after eight weeks of local vaginal estrogen therapy. Although the vagina, bladder, and gut microbiomes have been increasingly independently studied, less is known about the interactions of the bacterial communities among the three environments as well as the dynamic relationship with menopausal status and vaginal estrogen therapy and the investigators seek to elucidate these relationships further.
Read the detailed description
This is an open-label pilot study of vaginal estrogen therapy in postmenopausal participants with vulvovaginal atrophy. The investigators seek to evaluate the effects of vaginal estrogen therapy on the vaginal, urinary, and rectal bacterial communities (microbiomes) and assess the (i) quantitative change in relative abundance of Lactobacillus among the community composition of bacteria in the vagina, and (ii) to evaluate the vaginal maturation index (VMI), vaginal pH, and vaginal inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF (IL - Interleukin, TNF - tumor necrosis factor, MCP - monocyte chemoattractant protein, GM - granulocyte macrophage, CSF - colony stimulating factor) and correlate any notable changes with changes noted in the vaginal microbiome, and (iii and iv) observe for quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) among the bladder and rectal microbiomes. These changes will also be compared to the results yielded from the vaginal microbiome analysis. Additionally the investigators will assess for quantitative changes in the bladder and rectal inflammatory biomarkers (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF) and correlate these findings with any notable changes in the bladder and rectal microbiomes. Furthermore, changes in these biomarkers will be compared with the data (inflammatory and microbial) yielded from vaginal sampling. Bio-specimens and patient questionnaires will be assessed at baseline and again after eight weeks of vaginal estrogen therapy.
20 participants will receive the intervention (vaginal estrogen therapy) for 8 weeks. 5 participants who meet the same inclusion/exclusion criteria will not receive the intervention and will be sampled at the same time points. The additional 5 participants are intended to serve as a control cohort to demonstrate stability of the microbiome over the study period. The 5 participants may be compared to the 20 participants receiving therapy but that is not part of the primary or secondary outcomes.
The investigators believe that examining the dynamic relationships of the genitourinary-rectal region is innovative and vital to validating the investigator's understanding and assumptions of the pathophysiology and treatment approaches of this disorder.
- Conditions
- Female Urogenital Diseases, Vaginal Atrophy, Postmenopausal Atrophic Vaginitis, Genitourinary Disease, Postmenopausal Symptoms
- Being tested
- Conjugated Estrogens Cream
- Keywords
- Genitourinary Syndrome of Menopause, Vaginal Atrophy, Vaginal Estrogen Therapy, Inflammatory Response, Microbial Colonization, Urinary Microbiome, Vaginal Microbiome, Rectal Microbiome, Conjugated Estrogen Cream
- Medical subject headings
- Female Urogenital Diseases, Atrophic Vaginitis, Urogenital Diseases, Communicable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conjugated Estrogens CreamDrug
Also called Premarin Vaginal Cream
0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Conjugated Estrogens Cream | Experimental | 0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks Receives: Drug: Conjugated Estrogens Cream |
| Control Cohort | No intervention | No intervention will be given. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantitative Change in Relative Abundance of Lactobacillus Among the Community Composition of Bacteria in the Vagina
The relative abundance of the Lactobacillus genus, as measured by 16S ribosomal RNA (rRNA) gene sequencing, is the proportion of Lactobacillus genus among the total vaginal microbiome. After analysis of the gene sequencing, the total yield of bacteria at the genus level equals 1.
The quantitative change in relative abundance of Lactobacillus among the community composition of bacteria in the vagina will be assessed from baseline to 8 weeks. The investigators hypothesize that a pre-specified statistically significant quantitative increase in the relative abundance of Lactobacillus will be seen among the participants that receive treatment.
Measured: Baseline, 8 weeks
Secondary outcomes (3)
Change in Vaginal Maturation Index (VMI)
The maturation value (MV) is calculated with the following formula: MV = % surface cells + (0.5 × % intermediate cells).
The outcome data is reported as the delta change from baseline to 8 weeks.
The data for the primary outcome has been entered using the "measure type - NUMBER" because the outcome is a delta or change in the vaginal maturation index.
Measured: Baseline, 8 weeks
Change in Vaginal pH
Change in the vaginal pH from baseline to 8 weeks
Measured: Baseline, 8 weeks
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
Change in the vaginal inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF from baseline to 8 weeks
Measured: Baseline, 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2019
- Study start1 Aug 2019
- Primary completion14 Jan 2021
- Study completion14 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Female Urogenital DiseasesStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kyle P Norris, MD, University of Alabama at Birmingham
- Investigators
- Kyle P Norris, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03996603
- Sponsor's protocol ID
- IRB-300002968
- Acronym
- IMPLORE
- Status last verified
- Apr 2024
- First submitted
- 11 Jun 2019
- Last updated
- 7 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IMPLORE Study: Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy
- ClinicalTrials.gov ID
- NCT03996603
- Acronym / sponsor ID
- IMPLORE / IRB-300002968
- Conditions
- Female Urogenital Diseases, Vaginal Atrophy, Postmenopausal Atrophic Vaginitis, Genitourinary Disease, Postmenopausal Symptoms
- Keywords
- Genitourinary Syndrome of Menopause, Vaginal Atrophy, Vaginal Estrogen Therapy, Inflammatory Response, Microbial Colonization, Urinary Microbiome, Vaginal Microbiome, Rectal Microbiome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 14 Jan 2021 (actual)
- Study completion
- 14 Jan 2021 (actual)
- First posted
- 25 Jun 2019 (actual)
- Results
- Posted 7 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this proposed pilot study, 16S ribosomal RNA (rRNA) gene sequencing will be used in the analysis of bacterial communities (microbiomes) in postmenopausal women with vulvovaginal atrophy (VVA) before and after eight weeks of vaginal estrogen use. The investigators plan to characterize the composition and dynamics of the microbiomes of the vagina, bladder, and rectum for quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) before and after eight weeks of local vaginal estrogen therapy. Although the vagina, bladder, and gut microbiomes have been increasingly independently studied, less is known about the interactions of the bacterial communities among the three environments as well as the dynamic relationship with menopausal status and vaginal estrogen therapy and the investigators seek to elucidate these relationships further.
Detailed description
This is an open-label pilot study of vaginal estrogen therapy in postmenopausal participants with vulvovaginal atrophy. The investigators seek to evaluate the effects of vaginal estrogen therapy on the vaginal, urinary, and rectal bacterial communities (microbiomes) and assess the (i) quantitative change in relative abundance of Lactobacillus among the community composition of bacteria in the vagina, and (ii) to evaluate the vaginal maturation index (VMI), vaginal pH, and vaginal inflammatory biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF (IL - Interleukin, TNF - tumor necrosis factor, MCP - monocyte chemoattractant protein, GM - granulocyte macrophage, CSF - colony stimulating factor) and correlate any notable changes with changes noted in the vaginal microbiome, and (iii and iv) observe for quantitative and qualitative changes in the distribution of operational taxonomic units (OTUs) among the bladder and rectal microbiomes. These changes will also be compared to the results yielded from the vaginal microbiome analysis. Additionally the investigators will assess for quantitative changes in the bladder and rectal inflammatory biomarkers (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF) and correlate these findings with any notable changes in the bladder and rectal microbiomes. Furthermore, changes in these biomarkers will be compared with the data (inflammatory and microbial) yielded from vaginal sampling. Bio-specimens and patient questionnaires will be assessed at baseline and again after eight weeks of vaginal estrogen therapy.
20 participants will receive the intervention (vaginal estrogen therapy) for 8 weeks. 5 participants who meet the same inclusion/exclusion criteria will not receive the intervention and will be sampled at the same time points. The additional 5 participants are intended to serve as a control cohort to demonstrate stability of the microbiome over the study period. The 5 participants may be compared to the 20 participants receiving therapy but that is not part of the primary or secondary outcomes.
The investigators believe that examining the dynamic relationships of the genitourinary-rectal region is innovative and vital to validating the investigator's understanding and assumptions of the pathophysiology and treatment approaches of this disorder.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conjugated Estrogens Cream | Experimental | Drug: Conjugated Estrogens Cream0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks |
| Control Cohort | No intervention | –No intervention will be given. |
Who may qualify
- Ages
- 55 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Postmenopausal with vulvovaginal atrophy
- Age ≥55 years old and a screening vaginal pH of ≥5.
- Without menses for ≥12 months.
- No uterovaginal or vaginal vault prolapse beyond the hymen.
- No estrogen replacement within the last month (may come off current treatment, i.e. wash out, to join the study)
Key exclusion criteria (8 listed)
- Patients with BMI >35kg/m2
- Any patients with infections requiring antibiotic or antifungal therapy during the study period.
- Study patients may not use any vaginal suppositories, douches, or vaginal hygiene wipes within the month preceding enrollment. For patients already on hormone therapy, will be allowed to undergo a "wash out" period of estrogen or progesterone products for one month prior to enrollment.
- Additional exclusions included patients with systemic conditions requiring immunosuppressive drugs, currently receiving chemotherapy, or history of pelvic radiation.
- Any patients with contraindications to vaginal estrogen therapy including: vaginal bleeding of unknown etiology; known, suspected, or history of breast cancer or estrogen-dependent neoplasia; active DVT, PE, or h/o these conditions; active arterial thromboembolic disease (ie. stroke or MI) or h/o of these; known liver disease or thrombophilic disorders.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Conjugated Estrogens CreamAlso: Premarin Vaginal Cream0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks | Drug | Conjugated Estrogens Cream |
Primary outcome
Quantitative Change in Relative Abundance of Lactobacillus Among the Community Composition of Bacteria in the Vagina
Time frame: Baseline, 8 weeks
The relative abundance of the Lactobacillus genus, as measured by 16S ribosomal RNA (rRNA) gene sequencing, is the proportion of Lactobacillus genus among the total vaginal microbiome. After analysis of the gene sequencing, the total yield of bacteria at the genus level equals 1. The quantitative change in relative abundance of Lactobacillus among the community composition of bacteria in the vagina will be assessed from baseline to 8 weeks. The investigators hypothesize that a pre-specified statistically significant quantitative increase in the relative abundance of Lactobacillus will be seen among the participants that receive treatment.
3 secondary outcomes
Change in Vaginal Maturation Index (VMI)
Time frame: Baseline, 8 weeks
Change in Vaginal pH
Time frame: Baseline, 8 weeks
Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF
Time frame: Baseline, 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kyle P Norris, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Conjugated Estrogens Cream in people with Female Urogenital Diseases and Vaginal Atrophy, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantitative Change in Relative Abundance of Lactobacillus Among the Community Composition of Bacteria in the Vagina (time frame: Baseline, 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024.