Investigation of the Effect of the Female Urinary Microbiome on Incontinence (FUM)
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|ClinicalTrials.gov Identifier: NCT02835846|
Recruitment Status : Completed
First Posted : July 18, 2016
Last Update Posted : January 21, 2019
|Condition or disease||Intervention/treatment||Phase|
|Overactive Bladder Incontinence Nocturia||Drug: Estrogen Cream||Phase 4|
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. OAB affects approximately 31% of women over the age of 65. 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). The 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Long-standing medical dogma has been replaced by clear evidence that a female urinary microbiome (FUM) exists. The investigators recently reported that the FUM in women without OAB is less diverse than the FUM of women with OAB. The investigators soon will report that FUM status stratifies women with OAB into treatment response groups and women with less diverse FUMs are more likely to respond to anti-cholinergic OAB therapy (Thomas-White et al., in preparation). 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), the investigators reason the FUM would respond similarly to estrogen and become less diverse. Although transvaginal medications likely alter nearby bacterial niches (e.g. the bladder), no study has reported the urinary microbiomic response to vaginal estrogen.
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.
The investigators hypothesize that, following estrogen treatment of hypoestrogenic women with OAB, symptom improvement will be associated with 1) reduced FUM diversity, 2) alteration of other FUM characteristics and 3) increased AMP levels. The investigators propose two specific aims:
Aim 1: To compare pelvic floor microbiome (PFM) diversity and AMP levels before and after estrogen treatment in hypoestrogenic women with OAB symptoms.
Aim 2: Determine if FUM characteristics correlate with OAB symptoms.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||64 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Investigation of the Effect of the Female Urinary Microbiome on Incontinence|
|Actual Study Start Date :||September 2016|
|Actual Primary Completion Date :||March 2018|
|Actual Study Completion Date :||May 2018|
Experimental: Estrogen Arm
The intervention for this study is an estrogen cream (i.e., Premarin Cream®). Women in this study will receive this estrogen cream and apply it to their vagina twice weekly for 12 weeks
Drug: Estrogen Cream
Participants are provided a vaginal estrogen cream (i.e., Premarin Cream® 0.625 mg conjugated estrogen/gram) and instructed to use 0.5 grams with an applicator twice weekly for 12 weeks.
Other Name: Premarin Cream®
- Diversity of the pelvic floor microbiome (PFM) before and after treatment [ Time Frame: 12 weeks ]Diversity of the PFM will be measured as counts of microbial taxa. The investigators will compare participants' counts of microbial taxa before and after treatment.
- OAB symptoms before and after treatment [ Time Frame: 12 weeks ]OAB symptoms will be measured using the Overactive Bladder Questionnaire (OAB-q). The investigators will compare participants' OAB symptoms using the OAB-q before and after treatment.
- OAB Symptoms as a function of the PFM diversity [ Time Frame: 12 Weeks ]The investigators will determine whether any change in OAB symptoms using the OAB-q before and after treatment is moderated by the change in participants' counts of microbial taxa before and after treatment.
- Urothelial antimicrobial peptide (AMP) levels before and after treatment [ Time Frame: 12 weeks ]The investigators will compare participants' AMP peptide levels before and after treatment.
- OAB Symptoms as a function of AMP levels [ Time Frame: 12 weeks ]The investigators will determine whether any change in OAB symptoms using the OAB-q before and after treatment is moderated by the change in participants' AMP levels before and after treatment.
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): NCT02835846
|United States, Illinois|
|Loyola University Medical Center|
|Maywood, Illinois, United States, 60153|
|Principal Investigator:||Alan Wolfe, PhD||Loyola University|