Sacral Neuromodulation and the Microbiome

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.

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