Sacral Neuromodulation and the Microbiome

The Association Between the Urinary Microbiome and Response to Sacral Neuromodulation in Women With Urgency Urinary Incontinence

Sacral neuromodulation (SNM) which is approved as a treatment for men and women with urgency urinary incontinence (UUI), urgency frequency syndrome, urinary retention and anal incontinence, is a procedure designed to deliver electrical pulses to the sacral nerves, thereby influencing the bladder, sphincters, and pelvic floor. Although the success rates of this treatment are quite high, the precise mechanism of action of SNM in subjects with UUI remains unclear. Moreover, there are little data regarding specific patient characteristics that may serve as "predictors" for SNM success. Recent studies suggest that the bacterial community that lives in the urinary tract plays a role in the development and continuation of urinary symptoms. It is proposed that the urinary microbiome may change in women before and after SNM implantation and this study aims to describe these changes. Investigators in this study also hope to determine if differences in the urinary microbiome exist in women with a positive response to SNM treatment (responders) compared to those without symptom improvement (non-responders). This hypothesis will be tested by collecting urine samples as well as questionnaire and medical data from subjects with UUI that are already planning on undergoing SNM as part of clinical care before and after their SNM treatment.

Study Overview

• Status: Completed
• Conditions: Urgency Urinary Incontinence
• Intervention / Treatment: Device: InterStim Therapy

Detailed Description

One in four women reports bothersome symptoms of a pelvic floor disorder with 16% reporting urinary incontinence (UI). Sacral neuromodulation (SNM) which is approved for men and women with urgency urinary incontinence (UUI), urgency frequency syndrome, urinary retention and anal incontinence, is a procedure designed to deliver electrical pulses to the sacral nerves, thereby influencing the bladder, sphincters, and pelvic floor. SNM provides symptomatic relief in 70-86% of patients undergoing the procedure for UUI according to several recent prospective studies. Although the success rates are quite high, the precise mechanism of action of SNM in subjects with UUI remains unclear. Moreover, there are little data regarding specific patient characteristics that may serve as "predictors" for SNM success.

The microbiome refers to the genetic material of the micro-organisms present in a particular environment. The role of the microbiome has recently been implicated in several disease states (obesity, inflammatory bowel disease, and functional bowel disease. Initially, the urinary microbiome was not a part of the "human microbiome project" as it was widely accepted that urine is sterile. However, recent studies have noted the presence of a urinary microbiota in adult women without clinical urinary tract infections. Furthermore, recent studies have shown that the urinary microbiome differs among women with UUI versus those without UUI and also among women with interstitial cystitis / painful bladder syndrome versus those without it. These studies suggest that the urinary microbiome plays a role in the development and continuation of urinary symptoms.

Because of the invasiveness of the SNM procedure, it would be helpful to have a way to predict treatment success. Investigators in this study propose that the urinary microbiome may change in women before and after SNM implantation and hope to describe these changes by conducting this study. Investigators also hope to determine if differences in the urinary microbiome exist in women with a positive response to SNM treatment (responders) compared to those without symptom improvement (non-responders). This hypothesis will be tested by collecting urine samples from subjects with UUI that are already planning on undergoing SNM as part of clinical care before and after their SNM treatment.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women over the age of 18 with UUI planning to undergo placement of a sacral nerve modulator will be included if they have at least 2 UUI episodes on a 3-day diary.

Description

Inclusion Criteria:

• Women over the age of 18 with UUI planning to undergo SNM implantation will be included if they have at least 2 UUI episodes on a baseline 3-day diary.
• Willing and able to complete study visits, questionnaires and diaries
• Women previously treated with OAB medication are permitted to participate, but must be off of all medications for a minimum of 4 weeks prior to the performance of the baseline 3-day bladder diary and baseline assessments. They will be required to stay off any OAB medications for the duration of the study.

Exclusion Criteria:

• Neurologic disease (including multiple sclerosis, spinal cord injury, history of cerebrovascular accident, significant peripheral neuropathy)
• Pregnancy
• History of recurrent UTI in last 6 months by definition (3 culture proven UTI in 1 year or 2 culture proven UTI in 6 month period), or women who are receiving treatment for recurrent UTI
• Prolapse beyond the hymen
• Other contraindication to SNM
• Microscopic hematuria, as defined as 3 or more RBC/hpf on complete microscopic urinary analysis, without appropriate work-up (renal imaging and cystoscopy)
• History of pelvic radiation
• History of previous neuromodulation therapy including intravesical botulinum toxin, sacral neuromodulation or peripheral tibial nerve stimulation.

Deferral Criteria:

• Recent systemic antibiotic exposure (within the past 4 weeks)
• Urinary Tract Infection (UTI) at time of enrollment or sample

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
UUI patients undergoing SNM; Urine specimens, questionnaire, and medical data will be collected from subjects that have UUI and are undergoing InterStim placement (SNM).	Device: InterStim Therapy; Sacral Neuromodulation, delivered by the InterStim® System, offers long-term control of bladder control and bowel control symptoms through modulation of the nerves that help control the pelvic floor and lower urinary tract.; Other Names: Sacral Neuromodulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The abundance of bacteria associated with inflammatory processes in the urinary tract of women with a positive response to SNM (responders) versus those without symptom improvement (non-responders)	3 months after SNM treatment treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in the urinary microbial community of responders to SNM therapy	3 months after initiating SNM treatment

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: University of Missouri-Columbia; University of Pennsylvania; University of Washington; University of North Carolina; American Urogynecologic Society; Saint Francis Hospital and Medical Center
• Investigators: Principal Investigator: Margaret Mueller, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: July 12, 2016
• First Submitted That Met QC Criteria: July 13, 2016
• First Posted (Estimated): July 14, 2016

Study Record Updates

• Last Update Posted (Actual): November 18, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Urinary incontinence; Urinary microbiome; Urinary leakage; Sacral Neuromodulation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Elimination Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Incontinence; Enuresis
• Other Study ID Numbers: STU00202669

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No