Sacral Neuromodulation in Dual Incontinence: Ultrasound and Afferent Nerve Sensation Assessment
Phase: NA
Conditions: Dual Incontinence, Fecal Incontinence, Urinary Incontinence, Sacral Neuromodulation
Sponsor: Northwestern University

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Sacral Neuromodulation in Dual Incontinence: Ultrasound and 
Afferent Nerve Sensation Assessment
(SaNDI)
PRINCIPAL INVESTIGATOR: 
Kimberly Kenton, MD, MS
250 E Superior St, Suite 05-2370
Chicago, IL 60611
(312) 472 - 3874
(312) 472 - 3690
kkenton@nmff.org
SUB-INVESTIGATORS:
Margaret Mueller, MD
Bhumy Dave, MD
Alix Leader-Cramer, MD
Christina Lewicky-Gaupp, MD
Anne Marie Boller, MD
Northwestern University
PARTICIPATING SITES:
Northwestern University Feinberg School of 
Medicine
Department of Obstetrics and Gynecology
Prentice Women’s Hospital 
250 E Superior Street, Chicago, IL 60611
312 – 926 -4747
FUNDING AGENCY:
American Urogynecologic Society
IRB #: STU00098840 Approved by NU IRB for use on or after 7/31/2017 through 7/30/2018.

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Synopsis
Title
Sacral Neuromodulation in Dual Incontinence: Ultrasound and Afferent 
Nerve Sensation Assessment
Short Title
SaNDI
Protocol Date
July 7, 2014
Study Duration
1.5 years
Study Center(s)
Northwestern University Feinberg School of Medicine
Objectives
1) To quantify the effect of sacral neuromodulation (SNM) on 
afferent innervation using current perception thresholds (CPT) in 
women with dual incontinence (urgency urinary incontinence 
(UUI) and fecal incontinence (FI)).
2) To identify neurophysiologic predictors of successful SNM in 
women with dual incontinence.
3) To quantify and compare baseline urethral and anal sphincter 
anatomy as assessed by ultrasound in women with dual 
incontinence who undergo successful and unsuccessful SNM.
4) To assess the quality of sexual relationships in women with dual 
incontinence and their male partners and to identify specific 
areas of dysfunction that are common in these patients. 
Number of Subjects
30
Diagnosis and Main 
Inclusion Criteria
Women with responses of at least “moderate bother” to PFDI-20 items 
10 ‘do you lose stool beyond your control if your stool is loose or 
liquid” and 16 “do you experience urine leakage associated with a 
feeling of urgency that is a strong sensation of needing to go to the 
bathroom” will be identified through routine screening in our 
multidisciplinary clinic. 
Inclusion criteria: Women over the age of 18 with idiopathic dual 
incontinence planning to undergo placement of a sacral nerve modulator 
and will be included if they have at least 5 UUI episodes on a 3-day 
diary and 2 FI episodes on a 7-day diary. 
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TABLE OF CONTENTS
Synopsis...........................................................................................................................................2
1.0. Introduction – Background and Rationale...........................................................................4
1.1. Introduction
1.2. Background and Significance 
1.3. Preliminary Work
1.4. Innovation
2.0. Objectives.................................................................................................................................7
2.1. Primary Objectives
2.2. Secondary Objectives
3.0  Selection of Subjects ...............................................................................................................7
3.1. Inclusion Criteria
3.2. Exclusion Criteria
4.0  Subject Registration................................................................................................................8
4.1. Informed Consent (IC) and Institutional Review Board (IRB)
5.0  Study Design & Methods........................................................................................................9
5.1. Pre-Treatment Evaluation
5.2. Stage I Procedure – Test Phase
5.3. Stage II Procedure – Permanent Device Implantation
5.4. Three Month Follow up Visit
6.0  Statistical Plan.......................................................................................................................13
6.1. Statistical Analysis
6.2. Sample Size Determination
7.0  Data Collection & Record Keeping.....................................................................................13
7.1. Data Collection
7.2. Record Retention
8.0  References..............................................................................................................................15
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1.0.
 INTRODUCTION - BACKGROUND AND RATIONALE
1.1 Introduction
One in four women reports bothersome symptoms of a pelvic floor disorder with 16% 
reporting urinary incontinence (UI)1.  Likewise, 1 in 5 women with UI reports fecal 
incontinence (FI).  Women with dual incontinence (UI/FI) often have more bothersome 
symptoms, quality of life impact, and sexual dysfunction than those with just UI or FI.  
Sacral neuromodulation is the only currently available treatment with Level 1 
effectiveness data for BOTH UUI and FI.  Yet, the precise mechanism of action of SNM 
on UI and FI is unclear.  Alterations in both afferent innervation and muscular function 
are believed to play a critical role in etiology of UI and FI as well as patient’s response to 
various treatments.  This study aims to use innovative techniques to further our 
understanding of the neural and muscular alterations associated with dual incontinence 
AND identify potential neuromuscular mechanisms to guide treatment success.  We will 
also study the impact of dual incontinence on sexual function in women and their 
partners.  While many investigators have attempted to describe sexual function in women 
with UI and FI, few have addressed the impact the disorders may have on their partner’s.
1.2 Background and Significance
1.2.1
Impact of UUI/FI on Quality of Life & Sexual Function
At least 1 in 5 women reports bothersome urgency urinary incontinence (UUI) and/or 
fecal incontinence (FI) with even higher prevalence rates among the elderly1,2. In a large, 
national recent cross-sectional analysis, nearly 25% of women reported bother from at 
least one pelvic floor disorder1. Urgency urinary incontinence and FI each can impact 
women’s quality of life; however, the combination of both UUI and FI often results in 
even more dramatic effects on a woman’s quality of life3. Urinary urgency incontinence 
affects women’s sexual function, which often improves after treatment4.  Likewise, FI 
causes mental burden and emotional frustration and is also associated with decreased 
sexual function 5,6.  Although many studies evaluate SNS treatment efficacy and ability to 
improve quality of life, few have assessed adequately assessed sexual health.  The 
complex relationships between urinary incontinence and a woman’s self image, sense of 
well being, sexual activity, and sexual function is well established, and one can only 
assume the impact of FI or dual incontinence would be even more dramatic7,8.  Sexual 
dysfunction in the context of a relationship is a shared dysfunction.
Female partners of men with erectile dysfunction demonstrate high levels of sexual 
dysfunction9.  It is reasonable to suspect UUI and FI in women have an impact on the 
sexual function of their male partners9,10.
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1.2.2
Pathophysiology of UUI/FI and Mechanism of Action of SNM
The etiologies of UUI and FI are complex and likely multifactorial; however, 
increasing data suggests neuromuscular dysfunction, particular alterations in afferent 
nerves, plays a role in both.  SNM has proven effective for treatment of UUI and FI11,12. 
Electrical stimulation is thought to modulate afferent nerves and reflex pathways, which 
in turn influence urinary and fecal continence mechanisms.  The exact mechanism of 
SNM for the treatment of UUI and FI remains unclear and few data exist to guide which 
patients will respond to therapy.   Further characterization of neural function of patients 
who undergo successful SNM may provide insight into appropriate patient selection as 
well as advance our understanding of pathophysiology of incontinence and SNM 
treatment.
A systematic review evaluating SNM in the treatment of lower urinary tract 
dysfunction, concluded SNM was clinically effective (>50% improvement) in 60-90% of 
women with UUI13.  Similarly, a multi-center trial demonstrated SNM success rates of 
90% for women with FI (>50% reduction in FI episodes)11. Fecal incontinence symptoms 
improved in 49% of women with dual incontinence who underwent SNM primarily for 
UUI14.
Although SNM successfully improves UUI and FI in some women, there are no 
reliable predictors of successful symptoms resolution with SNM15,16. Women > 55 and/or 
with >3 co-morbid conditions have lower UUI cure rates following SNM15, however, 
clinical phenotypes of women who will respond to SNM are unknown.  Identification of 
quantifiable afferent neural and sphincter muscular parameters associated with successful 
SNM will aid patient selection as well as further understanding of pathophysiology of 
UUI/FI and mechanism of action of SNM in treating these disorders.  This novel 
approach is the first to quantify objective afferent neural function with validated clinical 
measures and 3-dimenstional ultrasound assessments of both the urethral and anal 
sphincters in women with dual incontinence.
1.3 Preliminary Work
Our team has extensive expertise and experience in neurophysiologic testing of the 
pelvic floor in women with urinary incontinence17. We showed improvement in urethral 
afferent sensation using CPT in women with UUI treated with tolterodine18. Urethral 
afferent sensation at stimulation frequencies corresponding to A-δ and C fibers improved 
after treatment, suggesting anticholinergic medications modulated urethral afferent 
innervation. 
Urethral morphology using 2-D US is different in women with detrusor overactivity 
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compared to controls19,1.  We recently demonstrated that urethral sphincter complex was 
easily and reproducibly quantified using 3-D US in women with UI20.
1.4 Innovation
1.4.1 Sensory Nerve Testing: Urethral and Anal Sphincters
Current Perception Threshold testing is a neurophysiologic test that uses electrical 
stimulation in the lower urinary tract to further clinical investigation of afferent 
innervation in pelvic floor dysfunction21,22. CPT testing reliably uses electrical stimuli at 
varying frequencies to activate different subpopulations of afferent nerve fibers21. A 
constant current electrical stimulator delivers sine wave stimuli at three different 
frequencies, which selectively depolarize different types of sensory nerves based on 
variations in membrane ion channel concentration. Large myelinated A- β fibers are 
stimulated at 2000 Hz, smaller myelinated A- δ are stimulated at 250 Hz and 
unmyelinated C fibers are stimulated at 5 Hz.  In vivo, A- δ fibers are activated by 
increased tension on the bladder wall and C-fiber activation is associated with some 
pathologic states23-25.  Multiple authors described CPT testing in the bladder and/or 
urethra of women with lower urinary tract problems26-28.  The use of CPT testing in the 
anus will be a novel approach to evaluate the afferent nerve function of the anus.
We hope that afferent nerve function assessment can be a useful predictor of those 
women who will positively respond to SNM for the treatment of dual incontinence.  This 
would alter treatment algorithm for women with UUI and FI and might potentially save 
women from undergoing an invasive procedure that is unlikely to improve their 
incontinence.
1.4.2
3-Dimentional Ultrasound Imaging: Urethral and Anal Sphincters
Ultrasound imaging of the internal and external anal sphincter as well as 
puborectalis are part of routine clinical care in women with FI.  In fact, ultrasound 
evidence of sphincter defect has been associated with more severe disease29.  Likewise, 
urethral morphology using 2-D ultrasound is different in women with detrusor 
overactivity compared to controls.  The urethral longitudinal smooth muscle thickness 
was decreased in women with detrusor activity19 suggesting that anatomic changes in 
urethral sphincter may be associated with UUI.
This proposal is highly innovative in that it addresses two common theories for 
etiology of UUI and FI in women:  neural and muscular disruption.  This study will 
capture 3-dimentional ultrasound imaging and measure small fiber afferent innervation to 
both the urinary and anal sphincter muscles. We will be able to determine associations 
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and relationships between sphincter size/volume and afferent nerve function in both the 
anal and urethral sphincters, which may further our understanding of the complex 
etiology of these disorders and aid in predicting treatment outcomes. 
2.0
OBJECTIVES
2.1. Primary Objectives:
2.1.1. To quantify the effect of sacral neuromodulation (SNM) on afferent innervation 
using current perception thresholds (CPT) in women with dual incontinence 
(urgency urinary incontinence (UUI) and fecal incontinence (FI)).
2.2. Secondary Objectives: 
2.2.1. To identify neurophysiologic predictors of successful SNM in women with dual 
incontinence.
2.2.2. To quantify and compare baseline urethral and anal sphincter anatomy as 
assessed by ultrasound in women with dual incontinence who undergo 
successful and unsuccessful SNM.
2.2.3. Women who undergo successful SNM will have larger urethral and anal 
sphincter muscles.
3.0.
SELECTION OF SUBJECTS
3.1 INCLUSION CRITERIA 
3.1.1. Subject is a female over the age of 18 years old
3.1.2. Subject is diagnosed with idiopathic dual incontinence
3.1.3. Subject is planning to undergo placement of a sacral nerve modulator
3.1.4. Subject has at least 5 UUI episodes on a 3-day diary
3.1.5. Subject has 2 FI episodes on a 7-day diary
3.1.6. Subject has given signed, informed consent prior to registration on study
 
3.2
EXCLUSION CRITERIA
3.2.1. Subject has a neurologic disease
3.2.2. Subject has a disease that may impair sphincter tone or sensation
3.2.3. Subject is pregnant
3.2.4. Subject has > Stage II pelvic organ prolapse
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3.2.5. Subject underwent rectal surgery in the past year
3.2.6. Subject has chronic inflammatory bowel disease
3.2.7. Subject has diathermy
3.2.8. Subject has QTc prolongation
3.2.9. Subject has cardiac arrhythmia
3.2.10. Subject has other contraindication to SNM.
4.0
SUBJECT REGISTRATION 
The Women’s Integrated Pelvic Health Program (IPHP) of Northwestern Medicine and 
Prentice Women’s Hospital is a multidisciplinary center with urogynecologists and colon and 
rectal surgeons specializing in pelvic floor disorders.  Women are referred for comprehensive, 
interdisciplinary evaluation and treatment. Consecutive women undergoing SNM for dual 
incontinence will be approached for study participation. Consenting participants will complete 
the short form of the Pelvic Floor Distress Inventory (PFDI-20) as well as 3-day urinary and 7-
day bowel diaries to determine eligibility. Women with responses of at least “moderate bother” 
to PFDI-20 items 10 ‘do you lose stool beyond your control if your stool is loose or liquid” and 
16 “do you experience urine leakage associated with a feeling of urgency that is a strong 
sensation of needing to go to the bathroom” will be identified through routine screening in our 
multidisciplinary clinic. 
4.1.
 Informed Consent (IC) and Institutional Review Board (IRB)
4.1.1. Subject Informed Consent
The Study Coordinator and Principal Investigator will write the Subject Informed 
Consent Form based off a Northwestern University approved template. The 
Subject Informed Consent document to be used in this study must be submitted to 
and approved by the Investigator’s IRB prior to screening any potential subjects.  
Any revisions to the written Informed Consent Form should receive IRB approval 
in advance of use. 
The Site is responsible for obtaining Informed Consent for each subject by having 
them sign the Subject Informed Consent Form prior to performing any test 
specifically for this study or collecting any data specific to this study. Informed 
consent will be obtained from the woman participating in the study as well as her 
partner, who will be filling out questionnaires.  Study specific activities include:

Current Perception Threshold Testing

GRISS Questionnaire
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
FiQOL Questionnaire
In obtaining and documenting informed consent, the Investigator must comply 
with the applicable regulatory requirement(s), and should adhere to GCP and to 
the ethical principles that have their origin in the Declaration of Helsinki.  
We will waiver the documentation of consent process for the male participants in 
this study. Their only requirement for participation in this study is to complete a 
questionnaire, which will be administered to them via an online survey through 
RedCAP, a secure data capture platform. They will receive an email containing 
the link to the survey, and the body of the email to the male participants will 
include an online consent document. The male participant will read through this 
consent and have the option to voluntarily complete the survey, or not to complete 
the survey by exiting out of the email. We will keep the written consent forms for 
males that do not have internet or email access. 
4.1.2. Institutional Review Board
The IRB is responsible for safeguarding the rights, safety, and well being of all 
subjects.  It is the responsibility of the Investigator to submit all required 
documentation to the IRB including the Investigational Plan and Subject Informed 
Consent Form.  Written documentation of approval of the Investigational Plan and 
Subject Informed Consent Form must be provided to the Sponsor before starting 
the registry.  
5.0 STUDY DESIGN & METHODS
Summary of Study Design:
Baseline
Test phase
3 month follow-up
Bladder/bowel diary
X
X
X
Multichannel 
urodynamics
X
Endovaginal and 
endoanal ultrasound
X
CPT testing
X
X
PFDI
X
X
FISI
X
X
FiQOL
X
X
PISQ-IR
X
X
GRISS
X
X
5.1. Pre-Treatment Evaluation/Baseline
Once the participant and her partner consent, they will undergo a standardized assessment. 
After the completion of the CPT testing and filling out the required surveys, the participant 
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will receive a $50 Prepaid gift card at this initial baseline visit.
5.1.1. Data Collected:
5.1.1.1. Age
5.1.1.2. Race/Ethnicity
5.1.1.3. Medical Co-morbidities
5.1.1.4. Prior UUI or FI treatments
5.1.1.5. Parity
5.1.1.6. Prior Surgery
5.1.2. Standardized Physical Examination Tools:
5.1.2.1. Pelvic floor muscle strength using the Oxford scale
5.1.2.2. Quantification of pelvic organ prolapsed using POPQ
5.1.2.3. Anal Sphincter Tone
5.1.3. Other Examinations Performed
5.1.3.1. 3-D Endovaginal ultrasound
3-D endovaginal ultrasound will be performed using a BK 8838 12mHz, 
360degress rotational transducer (BK Medical, Herlev, Denmark). Women will 
come in with a comfortably full bladder.  In dorsal lithotomy, the ultrasound 
probe will be inserted into the vagina without excessive pressure.  The correct 
anterior-posterior orientation will be noted using the hyperechogenic aspect of the 
pubic bone which will be designated the 12 o’clock position, with the anal canal 
at the 6 o’clock position. The operator will hold the transducer still during the 
image acquisition that will be performed at a length of 6 cm to scan for 60 
seconds.  This will yield a 3-D rendered cube to measure the urethra sphincter.  
This technique has previously been demonstrated30,31 
5.1.3.2. 3-D Endoanal ultrasound
3-D Endoanal ultrasound will be performed with a BK 2052 360degress 
rotational transducer (BK Medical, Herlev, Denmark).  Prior to the endoanal 
ultrasound exam, women will undergo a digital rectal exam to estimate the 
orientation of the anal canal. In the dorsal lithotomy position the probe is 
introduced along the axis of the anal canal until the puborectalis muscle sling is 
visualized. The anal canal, is divided into three sonographically distinct levels: 
high, mid, and low.  The 3-D rendered cube is obtained at the level of the high 
anal canal for measurement32. 
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5.1.3.3. Multichannel urodynamic testing: 
All women will undergo standard urodynamic studies according to 
International Continence Society guidelines.
5.1.3.4. Current Perception Threshold Testing*: 
Subjects will undergo CPT testing in a standardized fashion using a 
Neurometer CPT device in the dorsal lithotomy position. The 2000 Hz frequency 
will be tested first using the method of limits technique. Next, the amplitude is 
slowly increased until the stimulus is perceived. This is recorded as the upper 
limit. Then the stimulus is turned off until the initial sensation subsides. The same 
stimulus is then slowly decreased until the patient no longer perceives the 
stimulus. The last stimulus the patient can perceive is termed the lower limit. The 
upper and lower limits are then averaged to obtain the sensory threshold by the 
method of limits. The subject is then given a series of forced choice tests by the 
Neurometer to determine the sensory threshold by the method of levels starting at 
the lower limit obtained by the method of limits. The Neurometer randomly picks 
real and false stimuli separated by a 3–5 second rest period. The subject indicated 
which stimulus was stronger as the intensity was decreased by 0.4μA increments. 
Both the method of limits and the method of levels are then repeated at 250 Hz 
and 5 Hz.
5.1.4. Questionnaires and Surveys Administered
5.1.4.1. Pelvic Floor Distress Inventory (PFDI-20)33: 
A validated, condition-specific pelvic symptom questionnaire for 
quantification of pelvic symptoms 
5.1.4.2. Fecal Incontinence Severity Index (FISI)34: 
A validated questionnaire designed to capture the severity of fecal 
incontinence symptoms.
5.1.4.3. Pelvic Organ Prolapse Incontinence Sexual Questionnaire, IUGA-
revised (PISQ-IR)35:
 A validated condition-specific female sexual function questionnaire 
developed to assess sexual function in women with pelvic floor dysfunction.
5.1.4.4. Golombok Rust Inventory of Sexual Satisfaction (GRISS)36: 
A questionnaire developed by sex therapists in the UK in the 1970s for the 
assessment of the existence and severity of sexual problems39. It can be used to 
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assess the quality of the sexual relationship of a couple and of an individual’s 
function within a relationship. The GRISS is designated as Grade A (highly 
recommended) by the Fourth International Consultation on Incontinence. It is 
easily self administered, allowing for privacy for subjects completing the survey. 
It takes approximately 15 minutes to complete. The GRISS consists of seven 
domains, five of which are shared (Non-communication, Infrequency, 
Dissatisfaction, Avoidance, Non-sensuality) and two of which are gender specific 
(Vaginismus and Anorgasmia for women, Impotence and Premature Ejaculation 
for men). Raw scores are transformed to a scaled scores ranging from 1 to 9, with 
higher scores indicating greater sexual dysfunction. A range of 1 to 4 is 
considered non-problematic and scores greater than or equal to five are consistent 
with dysfunction. It is expected that a “normal”, functional relationship will yield 
at least one score of 5 on one of the domains. For this analysis, a score of 5 or 
more in any category was considered to be consistent with sexual dysfunction.
5.1.4.5. 3-day urinary and 7-day bowel diary 
5.1.4.6. Fecal Incontinence Quality of Life Questionnaire: 
A validated questionnaire assessing the impact of fecal incontinence on 
one’s quality of life.
5.2. Stage I Procedure – Test Phase
Study participants will undergo a staged implant procedure as previously described37,38.  
A quadripolar electrode (Medtronic) will be placed into the sacral foramen (confirmed with 
fluoroscopy) and connected via a percutaneous extension kit (Medtronic) to an external test 
stimulator (Medtronic) for approximately 7 days.  During the test period, patients will record 
bladder and bowel diaries.  If the number of incontinence episodes is reduced by 50% the 
patients will undergo placement of a permanent device, InterStim (Medtronic, Minneapolis, 
MN).
5.3. Stage II Procedure – Permanent Device Implantation
During Stage II, the patient will undergo implantation of the permanent sacral 
neuromodulator, InterStim, if symptoms showed 50% improvement during the test phase. 
This will require a 2-3 day stay in the hospital and will be performed under general 
anesthesia. 
5.4. Three Month Follow up Visit
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At the time of this visit, patients who did receive the implanted InterStim will receive an 
additional $50 Prepaid gift card for undergoing CPT Testing and filling out surveys at the 3 
month follow up visit. 
5.4.1. Questionnaires and Surveys Administered
5.4.1.1. Pelvic Floor Distress Inventory (PFDI-20)33
5.4.1.2. Fecal Incontinence Severity Index (FISI)34
5.4.1.3. Pelvic Organ Prolapse Incontinence Sexual Questionnaire, IUGA-revised 
(PISQ-IR)35:
5.4.1.4. Golombok Rust Inventory of Sexual Satisfaction (GRISS)36:
5.4.1.5. 3-day urinary and 7-day bowel diary
5.4.1.6. Fecal Incontinence Quality of Life questionnaire (FiQOL)
5.1.4.2. Other Examinations Performed
5.1.4.2. Current Perception Threshold (CPT) Testing
6.0.
STATISTICAL PLAN 
6.1. Statistical Analysis:
 
Each sensory modality threshold as determined at each of the different anatomic sites 
will be evaluated separately. Sensory thresholds will be compared before and after SNM 
placement using paired t-test.  Multivariate regression models will be used to determine 
clinical and neurophysiologic predictors of symptom improvement. Urethral sphincter 
volumes and presence/absence and size of internal and external anal sphincter defects will be 
compared in responders and non-responders.
6.2. Sample Size Determination: 
The sample size estimate was based off data from our prior work and urethral CPT in 
women with overactive bladder symptoms before and after treatment of tolteradine .  
Assuming a mean urethral CPT of 1.3 at 250 Hz prior to treatment and a mean of 0.75 after 
treatment with a standard deviation of 0.66 we estimate that 13 subjects are needed to show a 
significant difference with a 80% power at 5% significance level.  Assuming a 20% dropout 
rate, we will recruit 15 women and their partners.
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7.0.       DATA COLLECTION & RECORD KEEPING
7.1. Data Collection:
7.1.1. General Data Recording Instructions
Data Collection will occur in accordance with the registry specific monitoring and data 
management plans and will follow established SOPs.  A combination of web-enabled and 
centralized data management will be used. Data will be collected into an online Data 
Capture program called REDCap. This is a secure, web-based application used for the 
management and collection of data from surveys and questionnaires that are used in this 
study. This program will also help with the analysis and scoring of the data entered by the 
patients into the questionnaires and surveys. Reasons for missing data should be 
documented on the appropriate case report form.
 
7.2.
Record Retention
Participating Investigators/sites shall maintain accurate, complete, and current records 
relating to the participation in a safe and secure area: 

All correspondence with other Investigators/sites, or IRB.

Approved protocols and approved Informed Consent Forms.

Subject specific case report forms and supporting data including, signed and 
dated Consent Forms and medical records including; progress notes of the 
physician, the information and data on the condition of each Subject upon 
entering, and during the course of, the investigation, information about 
relevant previous medical history and the results of all diagnostic tests. 
Any paper documentation will be kept in a locked cabinet, separate from other 
study documents. Following completion of the study, all linking documents will be 
deleted from the hard drive and hard copies placed in a HIPPA approved container for 
shredding. 
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8.0
REFERENCES
1.
Nygaard I, Barber MD, Burgio KL, et al. Prevalence of symptomatic pelvic floor 
disorders in US women. JAMA 2008;300:1311-6.
2.
Visco AG, Brubaker L, Richter HE, et al. Anticholinergic therapy vs. 
onabotulinumtoxina for urgency urinary incontinence. N Engl J Med 2012;367:1803-13.
3.
Miner PB, Jr. Economic and personal impact of fecal and urinary incontinence. 
Gastroenterology 2004;126:S8-13.
4.
Rogers R, Bachmann G, Jumadilova Z, et al. Efficacy of tolterodine on overactive 
bladder symptoms and sexual and emotional quality of life in sexually active women. Int 
Urogynecol J Pelvic Floor Dysfunct 2008;19:1551-7.
5.
Cichowski SB, Komesu YM, Dunivan GC, Rogers RG. The association between fecal 
incontinence and sexual activity and function in women attending a tertiary referral center. Int 
Urogynecol J 2013.
6.
Imhoff LR, Brown JS, Creasman JM, et al. Fecal incontinence decreases sexual quality of 
life, but does not prevent sexual activity in women. Dis Colon Rectum 2012;55:1059-65.
7.
Salonia A, Zanni G, Nappi RE, et al. Sexual dysfunction is common in women with 
lower urinary tract symptoms and urinary incontinence: results of a cross-sectional study. Eur 
Urol 2004;45:642-8; discussion 8.
8.
Coyne KS, Matza LS, Brewster-Jordan J. "We have to stop again?!": The impact of 
overactive bladder on family members. Neurourol Urodyn 2009;28:969-75.
9.
Fisher WA, Rosen RC, Eardley I, Sand M, Goldstein I. Sexual experience of female 
partners of men with erectile dysfunction: the female experience of men's attitudes to life events 
and sexuality (FEMALES) study. J Sex Med 2005;2:675-84.
10.
Shabsigh R, Anastasiades A, Cooper KL, Rutman MP. Female sexual dysfunction, 
voiding symptoms and depression: common findings in partners of men with erectile 
dysfunction. World J Urol 2006;24:653-6.
11.
Wexner SD, Coller JA, Devroede G, et al. Sacral nerve stimulation for fecal 
incontinence: results of a 120-patient prospective multicenter study. Ann Surg 2010;251:441-9.
12.
Schmidt RA, Jonas U, Oleson KA, et al. Sacral nerve stimulation for treatment of 
refractory urinary urge incontinence. Sacral Nerve Stimulation Study Group. J Urol 
1999;162:352-7.
13.
Monga AK, Tracey MR, Subbaroyan J. A systematic review of clinical studies of 
electrical stimulation for treatment of lower urinary tract dysfunction. Int Urogynecol J 
2012;23:993-1005.
14.
Caremel R, Damon H, Ruffion A, et al. Can sacral neuromodulation improve minor 
incontinence symptoms in doubly incontinent patients successfully treated for major 
incontinence symptoms? Urology 2012;79:80-5.
15.
Amundsen CL, Romero AA, Jamison MG, Webster GD. Sacral neuromodulation for 
intractable urge incontinence: are there factors associated with cure? Urology 2005;66:746-50.
16.
Yazdany T, Bhatia N, Nguyen J. Determining outcomes, adverse events, and predictors 
of success after sacral neuromodulation for lower urinary disorders in women. Int Urogynecol J 
2011;22:1549-54.
17.
Gleason JL, Kenton K, Greer WJ, et al. Sacral neuromodulation effects on periurethral 
sensation and urethral sphincter activity. Neurourol Urodyn 2013;32:476-9.
18.
Kenton K, Lowenstein L, Brubaker L. Tolterodine causes measurable restoration of 
urethral sensation in women with urge urinary incontinence. Neurourol Urodyn 2010;29:555-7.
IRB #: STU00098840 Approved by NU IRB for use on or after 7/31/2017 through 7/30/2018.

Version Date:  April 19, 2017
- 16 -
19.
Major H, Culligan P, Heit M. Urethral sphincter morphology in women with detrusor 
instability. Obstet Gynecol 2002;99:63-8.
20.
Ramm O, Kenton K, Abernethy M, Mueller ER. 3D Ultrasonography of the female 
urethral sphincter. Poster 8, AUGS Annual Meeting, Chicgao IL, 2012.
21.
Olsen AL, Ross M, Stansfield RB, Kreiter C. Pelvic floor nerve conduction studies: 
establishing clinically relevant normative data. Am J Obstet Gynecol 2003;189:1114-9.
22.
Fujihara A, Ukimura O, Iwata T, Miki T. Neuroselective measure of the current 
perception threshold of A-delta and C-fiber afferents in the lower urinary tract. Int J Urol 
2011;18:341-9.
23.
Kenton K, Lowenstein L, Simmons J, Brubaker L. Aging and overactive bladder may be 
associated with loss of urethral sensation in women. Neurourol Urodyn 2007;26:981-4.
24.
Kenton K, Simmons J, FitzGerald MP, Lowenstein L, Brubaker L. Urethral and bladder 
current perception thresholds: normative data in women. J Urol 2007;178:189-92; discussion 92.
25.
De Laet K, De Wachter S, Wyndaele JJ. Current perception thresholds in the lower 
urinary tract: Sine- and square-wave currents studied in young healthy volunteers. Neurourol 
Urodyn 2005;24:261-6.
26.
Chung CP, Kuehl TJ, Spoonts KM, et al. Lack of preoperative predictors of the 
immediate return of postoperative bladder emptying after uterosacral ligament suspension. South 
Med J 2013;106:267-9.
27.
Davis C, Lowenstein L, Mueller E, Brubaker L, Kenton K. Measuring Urinary Sensation 
with Current Perception Threshold: A Comparison between Method of Limits and Method of 
Levels. Obstet Gynecol Int 2012;2012:868915.
28.
Ukimura O, Ushijima S, Honjo H, et al. Neuroselective current perception threshold 
evaluation of bladder mucosal sensory function. Eur Urol 2004;45:70-6.
29.
Papathanasopoulos A, Van Oudenhove L, Katsanos K, Christodoulou D, Tack J, Tsianos 
EV. Severity of fecal urgency and incontinence in inflammatory bowel disease: clinical, 
manometric and sonographic predictors. Inflamm Bowel Dis 2013;19:2450-6.
30.
Santoro GA, Wieczorek AP, Shobeiri SA, et al. Interobserver and interdisciplinary 
reproducibility of 3D endovaginal ultrasound assessment of pelvic floor anatomy. Int 
Urogynecol J 2011;22:53-9.
31.
Shobeiri SA, White D, Quiroz LH, Nihira MA. Anterior and posterior compartment 3D 
endovaginal ultrasound anatomy based on direct histologic comparison. Int Urogynecol J 
2012;23:1047-53.
32.
Corton MM, McIntire DD, Twickler DM, Atnip S, Schaffer JI, Leveno KJ. Endoanal 
ultrasound for detection of sphincter defects following childbirth. Int Urogynecol J 2013;24:627-
35.
33.
Barber MD, Walters MD, Bump RC. Short forms of two condition-specific quality-of-life 
questionnaires for women with pelvic floor disorders (PFDI-20 and PFIQ-7). Am J Obstet 
Gynecol 2005;193:103-13.
34.
Rockwood TH, Church JM, Fleshman JW, et al. Patient and surgeon ranking of the 
severity of symptoms associated with fecal incontinence: the fecal incontinence severity index. 
Dis Colon Rectum 1999;42:1525-32.
35.
Rogers RG, Rockwood TH, Constantine ML, et al. A new measure of sexual function in 
women with pelvic floor disorders (PFD): the Pelvic Organ Prolapse/Incontinence Sexual 
Questionnaire, IUGA-Revised (PISQ-IR). Int Urogynecol J 2013;24:1091-103.
36.
Rust J, Golombok S. The Golombok-Rust Inventory of Sexual Satisfaction (GRISS). Br J 
Clin Psychol 1985;24 ( Pt 1):63-4.
IRB #: STU00098840 Approved by NU IRB for use on or after 7/31/2017 through 7/30/2018.

Version Date:  April 19, 2017
- 17 -
37.
Boyle DJ, Murphy J, Gooneratne ML, et al. Efficacy of sacral nerve stimulation for the 
treatment of fecal incontinence. Dis Colon Rectum 2011;54:1271-8.
38.
Mellgren A, Wexner SD, Coller JA, et al. Long-term efficacy and safety of sacral nerve 
stimulation for fecal incontinence. Dis Colon Rectum 2011;54:1065-75.
39. 
Rust J, Golombok S. The Golombok-Rust Inventory of Sexual Satisfaction (GRISS). Br J 
Clin Psychol 1985;24 ( Pt 1):63-4.)
IRB #: STU00098840 Approved by NU IRB for use on or after 7/31/2017 through 7/30/2018.