The Estrogen Impact on Overactive Bladder Syndrome: Female Pelvic Floor Microbiomes and Antimicrobial Peptides
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|ClinicalTrials.gov Identifier: NCT02524769|
Recruitment Status : Completed
First Posted : August 17, 2015
Results First Posted : April 15, 2021
Last Update Posted : April 15, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Overactive Bladder||Drug: conjugated estrogen||Not Applicable|
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Long-standing medical dogma has been replaced by clear evidence that a female urinary microbiome (FUM) exists.This suggests that the FUM is a factor in lower urinary tract symptoms (LUTS) and that FUM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 (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Estrogen Impact on Overactive Bladder Syndrome: Female Pelvic Floor Microbiomes and Antimicrobial Peptides|
|Study Start Date :||December 2015|
|Actual Primary Completion Date :||November 2016|
|Actual Study Completion Date :||June 2017|
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 Name: Vaginal estrogen Premarin Cream® 0.625 mg
- 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.
- 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.
- 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.
- 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.
- 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.
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|Ages Eligible for Study:||55 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Accepts Healthy Volunteers:||No|
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02524769
|United States, Illinois|
|Loyola University Medical Center|
|Maywood, Illinois, United States, 60153|
|Principal Investigator:||Cynthia Brincat, MD||Loyola University|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Elizabeth Mueller, M.D. PhD, Loyola University|
|Other Study ID Numbers:||
|First Posted:||August 17, 2015 Key Record Dates|
|Results First Posted:||April 15, 2021|
|Last Update Posted:||April 15, 2021|
|Last Verified:||March 2021|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
Urge Urinary Incontinence
Urinary Bladder, Overactive
Urinary Bladder Diseases
Lower Urinary Tract Symptoms
Estrogens, Conjugated (USP)
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs