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

NCT03996603 | Completed Phase 4 Results FDA Drug

• 1 other identifier: IRB-300002968
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

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; Conjugated Estrogen Cream

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, 8 weeks

Secondary Outcomes (3)

• Change in Vaginal Maturation Index (VMI)

  Baseline, 8 weeks

• Change in Vaginal pH

  Baseline, 8 weeks

• Vaginal Inflammatory Biomarkers: IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF

  Baseline, 8 weeks

Other Outcomes (4)

• Quantitative and Qualitative Changes in the Distribution of Operational Taxonomic Units (OTUs) in the Bladder Microbiome.

  Baseline, 8 weeks

• Quantitative and Qualitative Changes in the Distribution of Operational Taxonomic Units (OTUs) in the Rectal Microbiome.

  Baseline, 8 weeks

• Bladder Inflammatory Biomarkers (IL-1B, IL-4, IL-6, IL-8, IL-10, TNF-a, MCP-1, GM-CSF)

  Baseline, 8 weeks

Study Arms (2)

Conjugated Estrogens Cream

EXPERIMENTAL

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

Drug: Conjugated Estrogens Cream

Control Cohort

NO INTERVENTION

No intervention will be given.

Interventions

Conjugated Estrogens Cream DRUG

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

Also known as: Premarin Vaginal Cream

Conjugated Estrogens Cream

Eligibility Criteria

• Age: 55 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

MeSH Terms

Conditions

Female Urogenital Diseases; Atrophic Vaginitis; Urogenital Diseases; Communicable Diseases

Condition Hierarchy (Ancestors)

Female Urogenital Diseases and Pregnancy Complications; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Genital Diseases; Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Kyle Norris, MD Principal Investigator
• Organization: University of Alabama at Birmingham

kyleparkernorris@gmail.com

(205) 934-1704

Study Officials

• Kyle P Norris, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor Fellow

Study Record Dates

• First Submitted: June 11, 2019
• First Posted: June 25, 2019
• Study Start: August 1, 2019
• Primary Completion: January 14, 2021
• Study Completion: January 14, 2021
• Last Updated: May 7, 2024
• Results First Posted: May 7, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)