Investigation of Microbiomes of Postmenopausal Women Looking for Outcomes and Response to Estrogen Therapy

NCT ID: NCT03996603

Last Updated: 2024-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2021-01-14

Brief 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. 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.

Conditions

Female Urogenital Diseases; Vaginal Atrophy; Postmenopausal Atrophic Vaginitis; Genitourinary Disease; Postmenopausal Symptoms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Conjugated Estrogens Cream

0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks

Group Type: EXPERIMENTAL

Conjugated Estrogens Cream

Intervention Type: DRUG

0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks

Control Cohort

No intervention will be given.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Conjugated Estrogens Cream

0.625mg/1g cream, 1g applied vaginally nightly for 2 weeks then 2x/week for 8 weeks

Intervention Type: DRUG

Other Intervention Names

Premarin Vaginal Cream

Eligibility Criteria

Inclusion Criteria

• 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)

Exclusion Criteria

• 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)

• Minimum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Kyle P Norris, MD

Instructor Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kyle P Norris, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB-300002968

Identifier Type: -

Identifier Source: org_study_id