Randomized Controlled Trial of PTNS Versus Sham Efficacy in Treatment of Bladder Pain Syndrome
Phase: NA
Conditions: Interstitial Cystitis Bladder Pain Syndromes
Sponsor: NYU Langone Health

Version Date: March 18, 2016, 
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Title of Study: “Randomized Controlled Trial of PTNS versus Sham Efficacy in Treatment of 
Bladder Pain Syndrome.”
Principal Investigator: Benjamin Brucker, MD
Study Number: s15-01447

PURPOSE OF THE STUDY AND BACKGROUND – 
o
Our primary aim in this pilot study is to evaluate the efficacy of the systematic 
effects of posterior tibial nerve stimulation (PTNS) treatment compared to an 
inactive sham intervention in female subjects with interstitial cystitis/bladder 
pain syndrome (IC/BPS) in an intent-to-treat analysis. Our primary outcome 
measure will be the Patient Global Impression of Improvement (PGI-I) a single 
item questionnaire assessing overall impression of improvement over time at the 
initial 12 weeks endpoint. 
o
Our secondary outcomes will include change from baseline in SF-12 quality of life 
scores, Visual Analog Scale (VAS) and O’Leary –Sant pain scores at 12 weeks To 
confirm the validity of the sham, subjects will be asked to identify which 
intervention they believed they received during the study at study conclusion. 
Additionally subjects will be presented with OAB-Q short forms. This will allow 
for evaluation of subjects with concomitant overactive bladder and painful 
bladder syndrome characteristics. 
o
We hypothesize that subjects randomized to the PTNS arm will demonstrate a 
greater improvement in both pain and quality of life scores, when compared 
with subjects who are randomized to the sham arm. Additionally, we 
hypothesize that the validity of the inactive sham intervention will be 
appropriately confirmed in our study population. 
 

Background: 

Bladder Pain Syndrome (BPS), which includes the sub-variant of interstitial cystitis (IC), is 
defined as “an unpleasant sensation (pain, pressure, discomfort) perceived to be related 

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to the urinary bladder, associated with lower urinary tract symptoms of more than six 
weeks duration, in the absence of infection or other identifiable causes”(1). 
Characteristically, it is pain lasting longer than 6 months, which is often refractory to 
treatment. BPS significantly impairs function of daily activities and is associated with 
decreasing ability to perform activities of daily living  (1,2).  A complete medical history 
including urinary and bowel symptoms, history of reproductive tract disease, 
psychoneurological disorders and musculoskeletal syndromes is key in patients who 
suffer from this disorder (6). It is important to consider psychological and social factors 
associated with BPS, in addition to possible physical causes. BPS is a diagnosis of 
exclusion and the symptoms cited are variable and have a wide-range. Additionally the 
etiology of this disease is unknown, making the development of directed therapies a 
challenge. BPS affects approximately 4.3% of patients in the United States who are seen 
in a primary care setting(3). The overall healthcare costs for women with a diagnosis of 
BPS are more than twice that of age matched controls. A woman with a diagnosis of BPS 
is expected to incur a mean cost of $6,614 a year, including $1,572 for medications and 
$3,463 for outpatient medical services (4,5). The adverse effects on a patient’s quality of 
life can be severe, and are similar to those reported for other chronic diseases such as 
congestive heart failure, Crohn’s disease and diabetes mellitus (5).  

How to effectively treat IC/BPS has remained a major challenge. Despite multiple 
modalities used to treat this syndrome including antihistamines, antidepressants, local 
anesthetics, neuromodulation, dietary and behavioral modifications and rarely surgery, 
many patients experience only short-term relief from these treatments and a large 
cohort of patients are refractory to these treatment options and resort to using a 
combination of therapies (5). In a recent Gallop poll of 5,325 US women concerning 
generalized pelvic pain,  11% of those polled limited their home activity, 11.9% limited 
their sexual activity, 15.8% took medication, and 3.9% missed at least 1 day of work per 
month due to the condition (6). The true incidence and prevalence of BPS are unknown 
due to the difficulty of diagnosis, however pelvic pain is a common problem 
encountered in the healthcare field and this poll reveals that currently available 
treatments do not adequately manage patient symptoms. 

Posterior tibial nerve stimulation (PTNS) is a minimally invasive method of 
neuromodulation, originating from traditional Chinese medicine. The technique 
identifies an acupuncture point that lies over the tibial nerve, and this point together 
with points at sacral and pubic sites have been used to treat pelvic disorders. McGuire 
and colleagues first tested this point as treatment for detrusor instability and found a 
decline in urinary urgency symptoms in this patient population (7,8). Since then, 

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multiple other trials have studied PTNS as a potential treatment for overactive bladder 
(OAB), chronic prostatitis, fecal incontinence, bladder pain syndromes or sexual 
dysfunction (9-12). PTNS has also been tested as a method to manage generalized pelvic 
pain, and favorable results have been demonstrated (13-15). To date, however, there is 
a paucity of robust literature on PTNS treatment for bladder pain specifically, and 
currently there are no randomized controlled trials comparing long-term effects of PTNS 
with control group. An evaluation of the literature revealed that more studies are 
required to understand the potential role for PTNS in the treatment of BPS (16). A sham 
PTNS model was recently validated as a mode to help identify the true efficacy of PTNS 
on overactive bladder and other disorders. Peters and colleagues found that patients 
were unable to identify the sham model correctly, resulting in a validated model to use 
when comparing PTNS treatment to placebo (17). There are few studies in the literature 
comparing PTNS to sham. One study revealed that PTNS is superior in the OAB 
population when compared with sham, however there is a paucity of data looking at the 
placebo effect in neuromodulation therapies in general and how this can specifically 
affect PTNS results (18-19). Additionally, there have been no trials looking at PTNS 
versus placebo for the treatment of BPS. Given the high rate of efficacy of placebo in 
pain syndromes, the lack of robust randomized controlled trials in this area inhibits our 
ability to understand whether PTNS is truly an effective treatment for BPS. 

Innovation:

There are currently multiple accepted treatment methods for BPS. Recently, in addition 
to medical therapies, neuromodulation techniques have been described for treatment 
of bladder pain, both in the form of percutaneous nerve stimulation (PTNS) and sacral 
neuromodulation (SNM). Both of these techniques are FDA approved treatments for 
other pelvic floor disorders such as OAB and fecal incontinence. While there is some 
literature to suggest that SNM therapies are associated with higher rates of efficacy, this 
therapy is more invasive when compared to PTNS and has been associated with 
significantly higher costs. 

In addition to the aforementioned PTNS trials, there have been some reports on the 
benefit of SNM treatments, although the data is sparse and there are no direct 
comparisons of SNM with PTNS for the management of bladder pain (20-21). It seems 
imperative that we continue to study the effects of PTNS on bladder pain, so we can 
better understand the role of this treatment for our patients, and better recognize the 
characteristics of the patient population that would obtain the greatest benefit. 
Furthermore, once the efficacy of PTNS is better defined, a future direction comparing 
different modes of neuromodulation to assess presence of superiority in treatment 

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could be undertaken. The estimated cost of PTNS is approximately $1,800 for 12 
sessions, which is the approved number of sessions currently outlined in the FDA usage 
of PTNS for other pelvic floor disorders. In contrast, the cost of sacral nerve stimulation 
is significantly higher. A recent study comparing costs of neuromodulation therapies for 
OAB revealed that cost after completing initial therapy with PTNS was $4867.00 while 
completion of SNM implantation and initial treatment cost an average of $24,342.00. 
Additionally, it was found that both methods had high levels of adherence, reaching 
71% and 90%, respectively, however data revealed an incremental cost-effectiveness 
ratio of $99,872 in favor of PTNS (22). The proposed study can provide critical data to 
build cost-effectiveness models that will help answer important questions as health care 
resources become more limited. PTNS, if proven effective for treatment of bladder pain 
syndromes, could improve quality of life for many of the approximately 7 million women 
in the United States who are affected by bladder pain. Cost-effectiveness data may lead 
to savings that are significant to the healthcare system.   A longer term look at the 
persistence of treatment will factor into this model as many patients with bladder pain 
are involved in a clinical paradigm, which includes multiple office and emergency room 
visits due to titration of analgesic interventions, etc. If PTNS proves to be an efficacious 
and has medium and long-term benefit for the treatment for BPS, this could result in 
even more cost savings for the healthcare system and the patient. This study is the first 
step to an accurate cost-analysis study in BPS. 

Study Design: This is a prospective, single center, double-blind, randomized, controlled 
trial comparing the efficacy of percutaneous tibial nerve stimulation to sham in the 
treatment of Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) through 12 weeks of 
therapy. 

Investigational Device : The device used will be the NUROTM Neuromodulation system, 
Medtronic Device Model # 3533, which is a non-implanted peripheral electrical 
continence device. The NURO neuromodulation system (stimulator model NURO 100) is  
currently FDA approved for use to treat patients with overactive bladder (OAB) and 
associated symptoms of urinary urgency, urinary frequency and urgency incontinence. 
As described previously in this document PTNS is widely used as an efficacious 
treatment for patients with lower urinary tract symptoms. It provides a minimally 
invasive alternative to sacral neuromodulation as it modulates the innervation of the 
bladder, urinary sphincter and pelvic floor peripherally. Given this, and the fact that 
many patients with bladder pain syndrome (BPS) have concomitant symptoms of 
urgency/frequency, it is reasonable to investigate the use of this product for treatment 
of bladder pain syndrome. While this has been described as a tool used for both BPS and 
chronic pelvic pain syndromes, there is a paucity of literature looking at this treatment 

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for these specific indications and more data needs to be collected (23). This device is of 
Non-significant risk due to the following:
o
This device is not implanted and is not represented to be for use supporting or 
sustaining human life.
o
While the device is for a use of substantial importance in treating disease there have 
been no previous studies identifying serious risk to the health, safety or welfare of a 
subject. Based on three randomized trials and one long term durability trial using PTNS, 
the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom 
issued guidance about this treatment technique stating “PTNS for OAB demonstrates 
effectiveness without major safety concerns”(24). The use of PTNS for Bladder Pain 
syndrome would be effectively the same use of the device, simply for another lower 
urinary tract symptom, bladder pain instead of overactive bladder. As discussed 
previously these symptom profiles often overlap in the community. In the previous 
studies using PTNS for bladder pain, no major adverse events were reported (18, 19, 
24). 
o
Adverse events associated with PTNS are reported as mild, transient and 
relatively uncommon and include bruising and/or bleeding at the needle site and 
tingling or mild pain at the needle site. These adverse events have been 
documented at an incidence of 1-2% (18,25). These adverse events are much 
more favorable than those of sacral neuromodulation, which is a current off-
label treatment used for bladder pain syndrome. Adverse events for sacral 
neuromodulation include pain at implant site, lead migration and infection, to 
name a few, with incidence rates of 5-15% (24-26). 
o
It is not purported or represented to be for use supporting or sustaining human 
life 
o
While it is desired that this device can be integral in providing improvement of 
symptoms, it is not used of substantial importance in diagnosing, curing, 
mitigating, or treating disease, 

CHARACTERISTICS OF THE RESEARCH POPULATION
o
Number of subjects: We aim to enroll 100 subjects in our study. Patients presenting 
to NYU Center for Female Pelvic Medicine and meet the inclusion criteria for the 
study will be recruited to participate in the study. 
o
Gender of Subjects: BPS/IC is a condition found predominantly in women and thus 
only female subjects will be recruited. 
o
Age of subjects: Subjects over the age of 18 will be recruited for the study. BPS/IC is 
a condition that generally does not afflict children and therefore they would be 
inappropriate to include in our study population. 
o
Racial and Ethnic Origin: There are no enrollment restrictions based upon race or 
ethnic origin for this study. All subjects meeting the inclusion criteria for the study 

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will be approached. The patient population of the NYU Center for Female Pelvic 
Medicine come from diverse backgrounds. BPS/IC is a condition that 
disproportionately affects Caucasian women over Hispanic or African American 
women (ref) and the racial makeup of our patient population reflects this. 
o
Inclusion Criteria: 

Women > 18 years old with visual analog scale > 5

Cessation of all analgesics or other medication for pain for at least 2 
weeks prior the PTNS intervention

Discontinuation of any other electrical stimulation methods 3 months 
prior to PTNS intervention

Capable of giving informed consent

Ambulatory

Capable and willing to follow all study-relation procedures 
o
Exclusion Criteria: 

Patients pregnant or planning to become pregnant during the study 
duration

Botox use in pelvic floor muscles within the last year

Current urinary or vaginal infections

Current use of Interstim device

History of a cardiac pacemaker

Diagnosis of neuropathy
o
Vulnerable Subjects: No vulnerable subject populations based on federal regulations 
are included in this trial. Children and fetuses are not affected by this disease, 
pregnant women are not PTNS candidates, and prisoners are not treated at the 
study site. The elderly are a potential, albeit likely small proportion of the patients 
with the diagnosis of BPS, thus they need to be included in our study population to 
make the results useful in clinical practice. They will be included in our study; 
however those who are no longer able to provide consent for themselves will be 
excluded.

 METHODS AND PROCEEDURES
o
Methods and Procedures: 

Approach: 

All patients seen at New York University Center for Female Pelvic Medicine to in the 
Department of Urology who suffer from BPS/IC, as defined above, will be offered 

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participation in this prospective randomized controlled study. 
o
Inclusion criteria will include: women > 18 years old with visual analog scale > 5, 
cessation of all analgesics or other medication for pain for at least 2 weeks prior 
the PTNS intervention, discontinuation of any other electrical stimulation 
methods 3 months prior to PTNS intervention, capable of giving informed 
consent, ambulatory, capable and willing to follow all study-relation procedures.
o
Exclusion criteria will include patients pregnant or planning to become pregnant 
during the study duration, Botox use in pelvic floor muscles within the last year, 
current urinary or vaginal infections, current use of Interstim, history of a cardiac 
pacemaker, diagnosis of neuropathy. 
o
Randomization will be carried out using computer-generated random 
allocations. A computerized random number generator will be used to generate 
a number 1-100. All odd numbers will be randomized to PTNS arm and all even 
numbers will be randomized to sham arm. This number will be generated by a 
co-investigator who is not involved in the consent process. He or she will provide 
an envelope revealing the randomization result to the investigator who is 
consenting the subject. Institutional Review Board approval from the NYU IRB 
will be obtained prior to starting the study. 

On-site training of investigators and research staff will include a study protocol lecture, 
demonstration of blinding apparatus setup, use of a standard PTNS system (needle, 
grounding pad and energy source) according to manufacturer instructions for use, and 
use of a TENS unit and placebo needles (for sham subjects). Subjects and study 
coordinators who will administer questionnaires will be blinded to the assigned 
treatment intervention throughout the trial. All subjects will be randomized 1:1 at the 
first intervention visit to PTNS or sham using a random block design. During the 
intervention session subjects will be in a comfortable seated position and lower 
extremities will be blocked and draped from view. All subjects will have three electrode 
pads placed to standardize the perception of the intervention between the 2 treatment 
arms. Next, instead of the inactive grounding pad used on the PTNS leg, the sham 
subjects will have an active adhesive pad placed on the bottom of the foot just below 
the smallest toe. This spot was chosen, as described in sham validation (17) since it is 
not part of the acupressure or acupuncture nerve pathway connected to the bladder, 
pelvis or any major organs. All subjects will be informed that they may or may not feel a 
sensory stimulus effect on their lower extremities as a result of the intervention. 
Subjects in both study groups will receive 12 weekly 30-minute intervention sessions 
and will be queried about adverse events. Evaluation of primary end point will be done 
on a weekly basis. Every two weeks the individual response to this parameter will be 

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assessed. Additionally, the overall change in primary endpoint will be evaluated at week 
12. The secondary endpoints will be evaluated at week 12 as well. There will be a 
debriefing at week 12 after the study has been completed, to reveal to the subject 
which arm they were in. 

PTNS group:
o
The medial aspect of the lower extremity will be palpated and a needle insertion 
site will be identified approximately 5 cm cephalad from the medial malleolus 
and slightly posterior to the tibia. Between the posterior margin of the tibia and 
the soleus muscle, a 34-gauge acupuncture-like needle will be inserted 
approximately 3–4 cm deep to the tibial nerve. An adhesive grounding pad will 
be placed on the bottom of the foot just below the smallest toe. An inactive 
adhesive grounding pad will be placed on the top of the foot just above the small 
toe to be consistent with the sham pad placement. The needle and grounding 
pad will be connected to the stimulator and the stimulation will be increased 
from 0 to 10 mA as tolerated. Flexion of the greater toe and sensory stimulation 
in the bottom of the foot will be used to confirm proper needle placement. The 
needle will be taped in place. The electrical current will be set at an intensity that 
is well tolerated by the subject and the mA  will be recorded on a subject report 
form. A 30-minute stimulation session will be given at 20 Hz. At the end of the 
procedure, the needle and grounding pad will be removed and discarded.

Sham group:
o
The medial aspect of the lower extremity will be palpated and a needle insertion 
site will be identified approximately 5 cm cephalad from the medial malleolus 
and slightly posterior to the tibia. Between the posterior margin of the tibia and 
the soleus muscle a sham needle will be used at the tibial nerve insertion site. 
This will stimulate needle placement without puncturing the skin. The needle will 
be taped in place, similar to the PTNS procedure. The “grounding pad” from the 
TENS unit device will be placed on the bottom of the foot just below the smallest 
toe. Another gel electrode will be placed on the top of the foot just above the 
small toe for conduction. The TENS electrode will be connected by lead wires to 
the TENS unit, set at 20 Hz (as in the PTNS group). The TENS unit will then be 
turned on and the stimulation will be increased tot the subject’s first sensory 
level. At the time the subject senses localized stimulation to either the bottom of 
the foot or the toe the TENS unit will be left on for a 30 minute test period. The 
TENS unit will then be removed and the needle will be removed and discarded. 

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
Sessions for both groups will be performed once per week for 30 minutes. The total 
treatment period will be 12 weeks. All patients will undergo thorough evaluation for 
bladder pain through a detailed history and physical exam (both general physical and 
gynecologic). Baseline characteristics will be collected. At the baseline of the study and 
at completion of the 12-week treatment all patients still enrolled will be asked to fill out 
general and disease-specific pain and quality of life questionnaires. We will use VAS and 
the O’Leary-Sant scores to determine pain intensity, location of pain and associated 
symptoms. The OAB-Q will be used to identify characteristic features of associated 
bladder pain and OAB symptoms. The SF-12 scale will be used to evaluate quality of life 
of each subject at the three analysis intervals. Patient Global Impression of 
Improvement (PGI-I), a single item questionnaire assessing overall impression of 
improvement over time, will be administered at the initial  visit and each visit thereafter 
up through the 12 weeks endpoint. This will allow us to assess progress of the primary 
end-point week-by-week and overall from baseline to end of treatment. Additionally we 
will perform an analysis of analgesia use and other past treatments used for pain in this 
population. 

Full disclosure of research proposal and description of the two possible arms of 
randomization will be conducted with all participants in the form of both written and 
verbal communication. Our goal is to conduct this study at NYU Hospital and this will 
ensure a wide catchment area, including women of various ages, ethnic groups and 
socioeconomic backgrounds. No subject will be excluded based on race, age or 
ethnicity. Subjects will also have opportunities throughout the trial to voice any 
concerns regarding the study and all human subjects will be protected from foreseeable 
research risks, as this trial will undergo IRB approval prior to initial execution.
o
Data Analysis and Data Monitoring. 

The interventions applied in this study represent minimal risks to our 
subjects. Therefore a data monitoring committee will not be employed to 
monitor subject safety. The twelve (12) 30-minute PTNS sessions makes 
up the interventional portion of this study. There are no expected 
complications from a twelve (12) week PTNS treatment regimen beyond 
mild patient discomfort or mild bruising at the needle insertion site. The 
data that will be collected as part of the data safety monitoring plan will 
revolve around the PTNS and sham treatment sessions and patient 
experience with the PTNS and sham treatments. All data gathered 
beyond the PTNS vs Sham trial is purely observational. Patients 

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requesting to be removed from the study early and patient reports of 
pain associated with the treatments will be taken note of.  Dominique 
Malacarne will be responsible for monitoring the data. Dr. Malacarne is 
the primary contact for subjects and thus she will be aware of 
unanticipated problems and any adverse events as they occur. After each 
10 patients are enrolled, Dr. Brucker and Dr. Malacarne will review any 
adverse/unanticipated events or patients requesting early trial removal. 
Events causing serious injury would be unexpected and will be reported 
to the IRB. This is a relatively small study and thus there is no planned 
interval analysis of the data. 
o
Data Storage and Confidentiality. The research data will be stored in a database 
that is password protected in the NYU network drive. The patient data will 
entered into a coded database for the purposes analysis. Dominique Malacarne 
and Benjamin Brucker will have access to the decoding key for the purposes of 
collecting the follow up questionnaires and entering this data into the database. 

RISK/BENEFIT ASSESSMENT
o
Risk. The additional risk assumed by the subjects due to participating in the 
PTNS/Sham trial stems from the fact that they will potentially be randomized to 
the inactive sham treatment arm. The risks of PTNS in general are described 
above and again are uncommon (1-2%). The sham arm will hold similar yet likely 
even less common risks, as there will still be an initial needle prick using the 
sham needle but no puncture of the skin and needle will be retracted into the 
sham needle sheath. The possibility and nature of risk is thoroughly explained in 
the consent form that they are given prior to agreeing to study participation. 
o
Protection against Risks. In an effort to reduce risk and discomfort to the 
patient, the study needle, grounding pad and energy source will all be placed 
and controlled by an attending or fellow from the Female Pelvic Medicine and 
Reconstructive Surgery division of the Urology department. Additionally, 
questionnaires are as short as possible and a physician from the urology 
department will be available to answer questions at all times for the patient 
during their 12 sessions should the device or needle cause them discomfort or 
should they have any concern. Should patients desire to terminate the PTNS trial 
at any time, someone from the urology department will be made available to 
them to remove the needle and disconnect the device. The criteria for 

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termination of the trial will be patient inability to sustain treatment sessions or 
patient request to be removed. 
o
Potential Benefits to the Subjects. There are potential individual benefits to the 
subjects participating in this trial. The possible benefit would be improvement in 
bladder pain symptoms. This potential benefit could be greater in the PTNS 
versus sham group, however patients are aware of this prior to consenting to the 
study.

SUBJECT IDENTIFICATION, RECRUITMENT AND CONSENT/ASSENT
o
Method of subject Identification and Recruitment. Subjects presenting to NYU 
Urology Associates, Female Pelvic Medicine and Reconstructive Surgery (FPMRS) 
division, who meet the inclusion criteria, will be recruited to participate in this 
study during the enrollment period. Drs. Victor Nitti, Nirit Rosenblum, Benjamin 
Brucker, Scott Smilen Dianne Glass, Daniel Hoffman and Dominique Malacarne 
comprise the FPMRS division. Subjects will be identified by the treating physician 
and the treating physician will introduce the study and request permission for 
another member of the study team to approach the patient. In order to reduce 
undue influence over the patients, the primary treating physician will not recruit 
the subject to participate in the study. Recruiting will be performed either by a 
Fellow or another attending of Female Pelvic Medicine and Reconstructive 
Surgery division. Subjects will be assured that participation is completely 
voluntary and declining will not influence their care. 
o
Process of Consent. Consent to participate in the study will be performed by one 
of the physicians in the Female Pelvic Medicine and Reconstructive Surgery 
division. They are, Dominque Malacarne, Dianne Glass, Daniel Hoffman, Kimberly 
Ferrante, Victor Nitti, Nirit Rosenblum, Benjamin Brucker, or Scott Smilen.  Prior 
to the consent process a physical exam will need to be performed if there is not 
one documented from the last three months. At time of the consent process, the 
PTNS device and characteristics of the treatment sessions will be described to 
the subjects. It will be made clear to them that the PTNS trial is for research 
purposes and is not a part of their routine treatment algorithm. The physicians 
obtaining consent are well trained in the use of PTNS for FDA approved 
treatment of overactive bladder and will be able to answer general questions 
about PTNS that the subject may have. The additional time commitment of filling 
out surveys at baseline, each visit and at the 13th week will be discussed as well 

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as the commitment to possible randomization to inactive sham treatment arm. 
The majority of this patient population are English speaking. Should the subject 
require a translator, this will be noted on the consent and a signature of the 
translator will be obtained. 
o
Subject Capacity. Subjects without the capacity to consent for themselves will 
not be recruited to participate in this study. Any PTNS treatment trial requires 
that a patient be able to maintain appointments for treatment sessions 
accurately report on her symptoms associated with BPS/IC. 
o
Subject Comprehension. The PTNS/Sham trial is fairly straightforward.  The most 
difficult thing to describe to patients is the idea of being randomized to PTNS 
treatment or sham arms for the purpose of assessing PTNS as a viable treatment 
option for BPS/IC. A physician well trained in symptoms of BPS/IC and the 
characteristics of PTNS treatment sessions as well as understanding of the PTNS 
device will be obtaining consent and will be present at the time of treatment 
sessions. At any point during this process the subject can decline to continue to 
participate. 
o
 Debriefing Procedures. The treatment arm to which each subject is randomized  
will be withheld from the subject and thus debriefing will be required. This will 
be done at the end of the 12 week period after the patient has completed all 
questionnaires. The patient will be allowed to ask any questions and will be 
given ample time to do so. This session will be with one of the aforementioned 
physicians.
o
Documentation of Consent. Consent will be documented with the signature of 
the subject on a consent form. This form will be stored in the locked office of 
Benjamin Brucker. 
o
Cost to the Subject. There will be no costs incurred by the subject as a result of 
the study. All materials for the PTNS/Sham trial will be provided to the patient 
and will be paid for with Female Pelvic Medicine and Reconstructive Surgery 
research funds. 
o
Payment for Participation. Subjects will not be paid for their participation in this 
study. 

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References: 
1)Hanno P and Dmochowski R: Status of international consensus on interstitial 
cystitis/bladder pain  syndrome/painful bladder syndrome: 2008 snapshot. Neurourology 
and Urodynamics 2009; 28: 274. 
2) Hanno et al. Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome. AUA 
Guideline. September 2014. 
3) Rosenberg MT, Page S, Hazzard MA. Prevalence of interstitial cystitis in a primary care 
setting. Urology 2007;69(suppl 4):48Y52.
4) Clemens JQ, Meenan RT, Rosetti MC, et al. Costs of interstitial cystitis in a managed care 
population. Urology 2008;71(5):776, 80;discussion 780Y781.
5) Sairanen J, Leppilahti M, Tammela TL, et al. Evaluation of health-related quality of life in 
patients with  painful bladder syndrome/interstitial cystitis and the impact of four 
treatments on it. Scand J Urol Nephrol 2009;43(3):212Y219.
6.)Evaraert K, et al. (2001). The pain cycle: implications for the diagnosis and treatment of 
pelvic pain syndromes. In Urogunecol J Pelvic Floor Dysfunction 12 (1):9-14.
7) Adams, K. and Denmann MA. Bladder Pain Syndrome: A Review. Female Pelvic Medicine 
& Reconstructive Surgery & Volume 17, Number 6, November/December 2011.
8) McGuire et al. Treatment of motor and sensory detrusor instability by electrical 
stimulation. J Urol 1983; 129:78-79. 
9)van Balken et al. Sexual functioning in patients with LUT dysfunction improves after 
percutaneous tibial nerve stimulation. Int J Impot Res 2006; 18:470-475.
10)Beimans JMAE, van Balken MR 2012. Efficacy and Effectiveness of Percutaneous Tibial 
Nerve Stimulation in the Treatment of Pelvic Organ Disorders: A systematic review. 
Neuromodulation 2013; 16:25-34. 
11)de la Portilla F, Rada R, Vega J, Gonzalez CA, Cisheros N, Maldonado VH. Evaluation of 
the use of posterior tibial nerve stimulation for the treatment of fecal incontinence: 
preliminary results of a prospective study. Dis Colon Rectum 2009; 52:1427-1433. 
12)Zhao J, Bai J et al. Posterior tibial nerve stimulation twice a week in patients with 
interstitial cystitis. Urology 2008. 71:1080-1084. 

Version Date: March 18, 2016, 
14
13)van Balken MR, et al. Percutaneous tibial nerve stimulation as neuromodulative 
treatment for chronic pelvic pain. Eur Urol 2003; 43:158-163.
14) Kim S, Paick J, Ku J. Percutaneous posterior tibial nerve stimulation in patients with 
chronic pelvic pain: a preliminary study. Urol Int 2007; 78:58-62.
15) Gokyildiz S, Kizilkaya Beji N, Yalcin O, Istek A (2012) Effects of percutaneous tibial nerve 
stimulation therapy on chronic pelvic pain. Gynecol Obstet Invest 73 (2): 99-105.
16) Ragab et al. Evaluation of percutaneous tibial nerve stimulation for treatment of 
refractory painful bladder syndrome. Urology (2015).  
17) Peters et al. Validation of a Sham for Percutaneous Tibial Nerve Stimulation (PTNS). 
Neurourology and Urodynamics 28:58–61 (2009).
18) Peters et al. Randomized trial of percutaneous tibial nerve stimulation versus sham 
efficacy in the treatment of Overactive Bladder Syndrome: Results from the SUmiT Trial. 
Journal of Urology. 2010. 
19) Knowles et al. Percutaneous tibial nerve stimulation versus sham electrical stimulation 
for the treatment of faecal incontinence in adults (CONFIDeNT): a double-blind, multicenter, 
pragmatic, parallel-group randomized controlled trial. 2015. The Lancet. 
20) Fariello, JY, Whitmore K. Sacral Neuromodulation stimulation for IC/PBS, chronic pelvic 
pain, and sexual dysfunction. Int Urogynecol J 2010; 21 (12):1553-1558. 
21) Marcelissen T, et al. Sacral Neuromodulation as a Treatment for Chronic Pelvic Pain. 
Journal of Urology. Vol. 186, 387-393, August 2011
22) Martinson et al. Cost of Neuromodulation Therapies for Overactive Bladder: 
Percutaneous Tibial Nerve Stimulation Versus Sacral Nerve Stimulation. Journal of Urology 
(2013). Vol 189,210-216. 
23. Khan et al. Nerve Stimulation for Chronic Pelvic Pain and Bladder Pain Syndrome, a 
systematic review. Acta Obstet Gynecol Scand 2013; 92: 881-887. 
24. National Institute for Health and Clinical Excellence. Percutaneous tibial nerve 
stimulation for overactive bladder symptoms. 2010. 
25. deGroat, W., et al. Percutaneous tibial nerve stimulation: A clinically and cost effective 
addition to overactive bladder algorithm of care. Curr Urol Rep (2012). 13: 327-334. 
26. Kim, Ja Hong, et al. Sacral Neuromodulation for Refractory Overactive Bladder, 

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