Effectiveness of Bilateral PTNS Compared to Unilateral PTNS for the Treatment of Overactive Bladder/Urge Incontinence
Phase: NA
Conditions: Overactive Bladder Syndrome, Urinary Incontinence, Urge
Sponsor: Gnankang Sarah Napoe

Study Protocol: Effectiveness of Bilateral PTNS compared to Unilateral PTNS for the 
Treatment of Overactive Bladder/Urge IncoNtinence (BUTTON) 
 
Clinical trials: NCT 03535857 
 
Protocol Date: 4/30/2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Scientific Background 
Overactive bladder (OAB) is defined as a syndrome of urinary urgency, usually associated with 
frequency with or without incontinence (1). This syndrome is estimated to affect more than 16 % 
of the adult population (2) and has a significant impact on the quality of life of those affected by 
it (3). The treatment algorithm as recommended by the American Urologic Association includes 
starting with behavioral modifications then offering pharmacologic therapy if needed (4).  
Previous data show that adherence to pharmacologic therapy is low due to side effects and thus 
there is a high discontinuation rate (5).  One of the approved treatments with a low side effect 
profile is percutaneous posterior tibial nerve stimulation (PTNS) (4).   
The SUmiT trial, a randomized controlled study for OAB has shown that when compared to 
sham, PTNS demonstrated 54% improvement in symptoms subjectively as compared to 20% in 
the sham arm.  In addition, PTNS was associated with a better reduction of incontinence 
episodes and daily number of voids (6). 
The OrBIT study which randomized women with OAB to PTNS or extended release tolterodine 
found a larger number of women receiving PTNS (79.5% vs. 60 %) who reported significant 
improvement in symptoms (7).  
PTNS device has been cleared by FDA for the treatment of overactive bladder and urge urinary 
incontinence. It however does not state whether stimulation of the posterior tibial nerve should 
be performed unilaterally or bilaterally.   The above studies using PTNS have all involved 
unilateral percutaneous stimulation of the posterior tibial nerve.  We do not yet know whether 
bilateral stimulation produces a different result from the traditional unilateral stimulation.  
A study of sacral neuromodulation, also an approved second tier OAB treatment which 
stimulates the sacral nerve demonstrated that 76% of patients with bilateral lead implants had 
more than 50% improvement in overactive bladder symptoms as compared to 58% of those who 
had unilateral lead placement (8).  A percutaneous nerve evaluation pilot study for those who 
failed sacral neuromodulation revealed that a select group of patients benefited from bilateral 
stimulation (9).  There have been no bilateral PTNS studies for OAB to date. Though the 
colorectal literature suggests bilateral transcutaneous stimulation of the posterior tibial nerve 
improves fecal incontinence (10).  The aim of our study is to compare the effectiveness of 
bilateral tibial nerve stimulation versus unilateral tibial nerve stimulation in managing overactive 
bladder symptoms using PTNS device.  The study will not be evaluating the effectiveness of the 
device itself but rather comparing stimulation of one nerve versus two nerves using a device that 
is already on the market. 
Study Objectives 
Percutaneous tibial nerve stimulation (PTNS) is an accepted treatment for overactive bladder that 
can be accomplished in the office with minimal side effects.  It is currently carried out by 
stimulating one of the posterior tibial nerve unilaterally.    
The aim of this study is to determine whether bilateral percutaneous tibial nerve stimulation is 
more effective than unilateral stimulation.  

Patients with a diagnosis of overactive bladder or urge incontinence who have previously failed 
lifestyle changes and/or pharmacologic therapy will be offered percutaneous tibial nerve 
stimulation.  Enrolled patients will be randomized into two groups.  The control group will receive 
the traditional unilateral treatment of PTNS.  The intervention group will receive bilateral PTNS 
treatment during the study period.  Intervention success will be measured by an improvement in 
the scores on the overactive bladder questionnaire and incontinence impact questionnaire as well 
as a decrease in the number of daily voids, nocturia episodes as assessed by voiding diaries.  
Hypothesis 
Bilateral PTNS is more effective than unilateral PTNS at reducing symptoms of OAB. 
Primary Aim: Compare improvement of overactive bladder symptoms of participants receiving 
bilateral PTNS to those receiving unilateral PTNS using the overactive bladder questionnaire 
(OAB-q). 
Secondary Aim(s): 
1. Evaluate impact of OAB on quality of life using the incontinence impact questionnaire 
2. Compare the number of voids per 24-hour periods 
3. Compare the number of nighttime voids 
4. Compare the number of incontinence episodes 
 
Study Design and Methods: 
This will be a randomized study of patients with overactive bladder not naive to behavioral therapy 
and/or pharmacotherapy (or unable to tolerate or with contraindications to pharmacotherapy) with 
or without urge incontinence recruited through the outpatient offices of the Division of 
Urogynecology at Women and Infants Hospital and University of Pittsburgh Medical Center 
Magee-Womens Hospital.  The patients will be randomized to receiving unilateral or bilateral 
PTNS for 30 minutes weekly for a total of 12 weeks.  Though we considered the use of a sham 
needle to decrease participants’ bias in reporting their results, we have elected not to use a sham 
needle.  Since all participants will be naïve to PTNS, they are unable to gauge the amount of 
improvement they should have and therefore we can expect reported improvement to be accurate.  
Participants will be asked to complete a 2-day bladder diary at baseline and weekly as per routine 
PTNS care. Participants will also be asked to fill out a validated OAB symptom severity 
questionnaire (OAB-q) and the incontinence impact questionnaire (IIQ-7) at baseline (+/- 1 week), 
four weeks (+/- 1 week), eight weeks (+/- 1 week) and twelve weeks (+/- 1 week). 
Our primary outcome will be the improvement in symptom severity as measured by the OAB-q 
score. 
Secondary outcomes will include change in the number of daily voids, change in nocturia or night 
time voids, change in number of incontinence episodes as measured by the bladder diary and, 
impact in quality of life as demonstrated by change in score of the incontinence impact 
questionnaire, IIQ-7. 

All questionnaires collected from participants will be labeled with a unique study number and any 
participant identifiers on the questionnaires or voiding diary will be redacted prior to saving in a 
research folder in a locked drawer. 
Inclusion criteria  
Female patients over the age of 18 who have previously tried and failed, or were unable to tolerate, 
behavioral therapy. Patients will have to consent to participate in the study. Patients on 
pharmacologic therapy at the time of recruitment will continue their treatment.  
Exclusion criteria 
1. Pregnant patients 
2. Patients with pacemakers of implantable defibrillators 
3. Patients with neurogenic bladder 
4. Patients who have received Botox or have an implant for sacral nerve stimulation 
5. Patients with uncontrolled bleeding disorder 
6. Patients with unhealed ulcers or with leg edema surrounding medial malleolus  
Rationale for exclusion criteria 
PTNS is an approved procedure that was not previously studied in the pregnant population 
therefore we will exclude pregnant patients from this study. PTNS is the electrical stimulation of 
the tibial nerve through a needle and therefore it is unclear how this stimulation would interact 
with a pacemaker or implantable defibrillator.   
While patients with neurogenic bladder may have overactive bladder, the pathophysiology of their 
urinary frequency and incontinence is different therefore including them in this particular study 
has the potential to confuse the study results.  Botox and Interstim (implantable sacral nerve 
stimulator) are advanced overactive bladder therapies and are generally offered to those who have 
failed pharmacotherapy and PTNS and therefore PTNS is unlikely to be effective in participants 
that have failed more advanced therapies.  A needle is inserted through the skin for PTNS and thus 
PTNS conjures a potential for bleeding.   Therefore, those with bleeding disorders will be excluded.  
Electrical stimulation is sent to the tibial nerve through a needle and therefore leg ulcers and edema 
can potentially alter the stimulation received by the nerve. 
Sample Size calculations 
Based on the SUmiT trial results, we expect a decrease in OAB symptom severity of 36.7 with a 
standard deviation of 21.5 in the unilateral PTNS group.  If we estimate that the bilateral PTNS 
group will show at least 50 % improvement from the unilateral, then we should see an average 
decrease in in symptom severity of 55 in the bilateral PTNS group. 
 

Our sample size estimate based on 5% significance and 80 % power with a standard deviation of 
21.5 will be: 23 per group for a total of 46 participants.   
If we expect an attrition rate of about 10%, our goal is therefore to recruit a total of 50 participants 
with 25 participants in each arm.  
Statistical Analysis 
Descriptive statistics will be used to assess the balance of baseline characteristics between 
randomization groups: unilateral and bilateral PTNS groups.  The primary analysis will be intent-
to-treat.  At baseline, for both treatment groups, the Wilcoxon-rank sum test will be used for all 
continuous variables and Fisher’s exact test for all categorical variables. For the analysis of 
primary and secondary outcomes, we will compare the last measurement to the baseline 
measurement within and between treatment groups in OABq score, IIQ-7, daily number of voids, 
number of nighttime voids, and number of incontinence episodes between the unilateral and 
bilateral PTNS groups using a pairwise t-test (using a Bonferroni adjustment). These comparisons 
will result in three sub-analyses: the changes of the primary and secondary outcomes within the 
unilateral PTNS group, within the bilateral PTNS group, and between the groups (taking the 
differences between the baseline and last measurement between the groups).  
Recruitment and enrollment  
Patients with overactive bladder or urge urinary incontinence who have failed behavioral or 
pharmacologic therapy will have all advanced therapy options presented to them as part of their 
clinical care by their physician.  Those who choose to have PTNS will be approached about the 
study either by the physician or the research coordinator.  If the patient meets eligibility and 
wishes to participate, they will be consented. In addition, patients who present for their first 
PTNS visit but were not previously approached about this study will be asked about participating 
in the study and consented if they are willing 
Randomization 
Randomization has been performed by a member of the staff at Women and Infants Hospital not 
part of the research team. Randomization has been concealed in opaque envelopes. Assignment 
of the randomization envelope to each subject will occur after the patient has signed consent.  
Intervention   
There will be 12 weekly PTNS treatments of 30 minutes. At the first visit, the participant will 
complete the OAB questionnaire and the incontinence impact questionnaire.  This will be 
repeated at weeks 4, 8 and 12.  
Participants will also be asked to fill out a weekly 2-day bladder diary as is routinely done for 
PTNS which they will bring to their visit. The bladder diaries will be provided to the participants 
at the initial visit. Participants will be instructed to fill out the bladder diary for 48 hours 
including all fluid intake, voids and any leakage.   

Participants who are randomized to unilateral PTNS stimulation will have one ankle stimulated 
for 30 minutes weekly for a total of 12 sessions.  Participants who are randomized to bilateral 
stimulation will have both ankles stimulated simultaneously for 30 minutes weekly for a total of 
12 sessions.   
PTNS stimulation is performed with a fine needle electrode that is inserted just below the skin in 
the medial ankle. This needle electrode is connected to a handheld stimulator through a lead 
wire. The handheld stimulator is then used to administer electrical impulses to the needle 
electrode increasing the current to a level that leads to a motor response and is comfortable to the 
participant. 
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