The Estrogen Impact on Overactive Bladder Syndrome: Female Pelvic Floor Microbiomes and Antimicrobial Peptides

March 22, 2021 updated by: Elizabeth Mueller, Loyola University
The medical field is beginning to adopt treatments that alter an individual's microbiome to improve patient health; however, this approach has not been adopted for treatment of lower urinary tract symptoms (LUTS). Here, the investigators propose the first step in development of such a therapy. If the investigators hypothesis is correct, the investigators could change the first line of treatment for hypoestrogenic women and develop future therapies that modulate bacteria in the bladder to improve not only LUTS but also treatment response. This could lead to the first treatment for lower urinary disorders that incorporates a person's individual microbiome.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Overactive bladder (OAB) syndrome is characterized by the symptom complex of urinary urgency, usually with associated frequency and nocturia, with or without urgency urinary incontinence in the absence of infection or other pathology. Vaginal estrogen, a well-documented treatment for OAB in hypoestrogenic women, has been shown to improve symptoms of frequency, urgency and urgency urinary incontinence (UUI). Several theories have been proposed to explain the mechanism underlying estrogen's effect on lower urinary tract symptoms (LUTS). Investigators propose that estrogen treatment influences bacterial communities (microbiomes) in the vagina and bladder and alters urothelial and vaginal (AMPs); thereby improving OAB symptoms in hypoestrogenic women.

Long-standing medical dogma has been replaced by clear evidence that a female urinary microbiome (FUM) exists.This suggests that the FUM is a factor in lower urinary tract symptoms (LUTS) and that FUM diversity contributes to LUTS and treatment response, like the vaginal microbiome and its contribution to vaginal symptoms.

In hypoestrogenic women, the vaginal microbiome shifts from low diversity communities, commonly dominated by Lactobacillus, to more diverse communities dominated by anaerobes; this change can be reversed with estrogen treatment. Since the FUM of women with OAB includes bacteria similar to those of the vaginal microbiome (e.g. Lactobacillus, Gardnerella, and diverse anaerobes), investigators reason the FUM would respond similarly to estrogen and become less diverse. While almost nothing is known about urinary/vaginal microbiome interplay, even less is known about immune response modulation in the bladder and vagina. However, estrogen reduces the subsequent urinary tract infection (UTI) rate in hypoestrogenic women affected by recurrent UTI, and estrogen induces urothelial antimicrobial peptide (AMP) expression. Since AMPs exhibit microbicidal activity, stimulate inflammation, and facilitate epithelial barrier homeostasis, estrogen may work through AMPs as mediators to optimize microbial equilibrium.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

53 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Clinical diagnosis of Overactive bladder
  • Clinical diagnosis of Postmenopausal:
  • English language skills sufficient to complete questionnaires
  • Clinical indication for vaginal estrogen use
  • Not currently receiving vaginal estrogen therapy

Exclusion Criteria:

  • Currently on systemic hormone replacement therapy (HRT) Have been on HRT within the past three months
  • Clinical diagnosis of estrogen dependent malignancies
  • Allergy to local estrogen therapy
  • Insufficient language skills to complete study questionnaires
  • Women with active, urinary tract infection
  • Received antibiotics within the past two weeks
  • Clinical diagnosis of stage 3 or 4 pelvic organ prolapse
  • Patient unwilling to use vaginal estrogen preparation
  • Currently on anticholinergic medication Have received anticholinergic medication within the past three months
  • Previously failed two medications for treatment of OAB Previously received intra-vesicle botulinum toxin injections Previously had posterior tibial nerve stimulation Previously had implantation of sacral neuromodulator
  • Patients wishing to start anticholinergic medication at the initial encounter
  • Undiagnosed abnormal genital bleeding
  • Clinical diagnosis of deep vein thrombosis (DVT) Clinical diagnosis of pulmonary embolism (PE)
  • Clinical diagnosis of arterial thromboembolic disease
  • Clinical diagnosis of liver dysfunction or disease
  • Clinical diagnosis of protein C, protein S or antithrombin or deficiency other known thrombophilic disorders

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: conjugated estrogen
All patients in the study will receive 0.625 mg conjugated estrogen/gram to use 0.5 grams twice weekly with the applicator for 12 weeks.
Drug: conjugated estrogen
0.625 mg conjugated estrogen/gram and instructions to use 0.5 grams twice weekly with the applicator.
Other Names:
  • Vaginal estrogen Premarin Cream® 0.625 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Relative Abundance of Lactobacillus
Time Frame: 0, 12 weeks
The relative abundance of Lactobacillus to total microbes per sample was measured before and after treatment. The within-participant change in relative abundance of Lactobacillus was calculated subtracting pre-treatment from post-treatment.
0, 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in OAB Symptoms
Time Frame: 0, 12 weeks
OAB symptoms are measured using the Overactive Bladder Questionnaire (OAB-q). The OAB-q symptom score ranges from 0-100 with higher scores indicating greater symptom severity. A change score is calculated as the post-treatment score minus the pre-treatment score.
0, 12 weeks
OAB Symptoms Associated With Relative Abundance of Lactobacillus
Time Frame: 0, 12 weeks
The investigators will determine whether change in OAB symptoms using the OAB-q before and after treatment is associated with the change in participants' relative abundance of Lactobacillus before and after treatment. The OAB-q symptom score ranges from 0-100 with higher scores indicating greater symptom severity.
0, 12 weeks
Change in Urothelial Antimicrobial Peptide (AMP) Levels
Time Frame: 0, 12 weeks
The investigators will compare participants' AMP levels before and after treatment. AMP activity level is measured as bacterial growth inhibition in square millimeters normalized to the total peptide bond concentration. Change is calculated as the post-treatment AMP level minus the pre-treatment AMP level.
0, 12 weeks
Change in OAB Symptoms Associated With Change in AMP Levels
Time Frame: 0, 12 weeks
The investigators will determine whether any change in OAB symptoms using the OAB-q before and after treatment is associated with the change in participants' AMP levels before and after treatment. AMP activity level is measured as bacterial growth inhibition in square millimeters normalized to the total peptide bond concentration. The OAB-q symptom score ranges from 0-100 with higher scores indicating greater symptom severity.
0, 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loyola University

Investigators

  • Principal Investigator: Cynthia Brincat, MD, Loyola University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Actual)

November 1, 2016

Study Completion (Actual)

June 1, 2017

Study Registration Dates

First Submitted

August 7, 2015

First Submitted That Met QC Criteria

August 13, 2015

First Posted (Estimate)

August 17, 2015

Study Record Updates

Last Update Posted (Actual)

April 15, 2021

Last Update Submitted That Met QC Criteria

March 22, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 207152

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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