A Randomized Trial of Transcutaneous Nerve Stimulation for Overactive Bladder Patients
Phase: NA
Conditions: Overactive Bladder
Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

 
 
 
 
 
 
 
A Randomized Trial of Transcutaneous Nerve Stimulation for 
Overactive Bladder Patients  
 
Dr Blayne Welk 
Assistant Professor, Western University 
 
NCT 02511717 
March 1 2016 
 
 
 

 
1 
Statement of Objective 
To determine the efficacy of transcutaneous tibial nerve stimulation (using skin patch electrodes) 
for the treatment of women with clinical symptoms of overactive bladder. 
 
 
Background 
Overactive bladder is a clinical diagnosis characterized by “urinary urgency, often with frequency 
and nocturia, with or without urgency urinary incontinence”2. Approximately 16% of adult women 
meet the clinical definition for overactive bladder, and approximately 1/3 of them will have 
urgency incontinence3,4. While a small proportion of patients do see their symptoms resolve after 
a year, for the vast majority this is a chronic condition4,5. Although it is not inherently dangerous, 
overactive bladder is an important condition given its wide-ranging impact on overall quality of life 
and mental health3. The magnitude of impact across different domains of quality of life is similar 
to chronic diseases such as diabetes6. In addition, the financial impact is substantial; in the United 
States this has been estimated at $12 billion annually7. 
 
 
Hypothesis 
I hypothesize that the study protocol of transcutaneous tibial nerve stimulation performed at 
home during 30 minute sessions, 3x/week, for 12 weeks will be associated with a statistically 
significant improvement in overall bladder symptoms. 
 
Design and methodology 
Study design: This is a randomized, double blind, sham controlled clinical trial. The primary 
intervention is 30 minute sessions, 3x/week, for 12 weeks of transcutaneous tibial nerve 
stimulation sessions carried out at home. The sham intervention will consist of the same 
treatment schedule, except with the application of transcutaneous nerve stimulation to the lateral 
aspect of the lower leg, away from the tibial nerve. Patients will undergo a 12 week treatment 
course. The patient and the treating physician will be blinded to the group assignment of the 
patient. Randomization will be done using a random number generator, and study assignment will 
only be released at the end of the study. Only the study nurse instructing the patient on 
placement of the study electrodes will know the patient assignment. The effectiveness of our 
sham protocol will be evaluated with a question during week 2-3 asking if they think they are in 
the active or sham group. The study visit schedule is outlined in more detail in Appendix 2. 
 
Inclusion criteria 
1. Female, >18 years of age, with the clinical diagnosis of overactive bladder (based on the 
current ICS definition2). 
2. Failure of behavioral measures and pharmacologic therapy to adequately control 
overactive bladder symptoms. 
3. Baseline patient perception of bladder condition score of 2 or higher. 
 
Exclusion criteria 
1. Current or previous percutaneous or sacral neuromodulation therapy 
2. Stress predominant urinary incontinence 

 
2 
3. Newly added bladder medication or dose change with the last 2 months (Tamsulosin, 
Silodosin, Alfuzosin, Terazosin, Baclofen, Diazepam, amitriptyline, imipramine, DDAVP, 
tolterodine, oxybutynin, fesoterodine, darifenacin, solifenacin, trospium, mirabegron) 
4. Intravesical botulinum toxin use within the last 1 year 
5. Implanted pacemaker or defibrillator 
6. History of epilepsy 
7. Unable or unwilling to commit to study treatment schedule 
8. Pregnant, or possible pregnancy planned for the duration of the study period 
9. Active skin disease of the lower legs (dermatitis, cellulitis, eczema, trauma) 
10. Documented allergy to patch electrodes or their adhesive 
11. Abnormal sensory function of the lower limb 
12. Metallic implant within the lower limb 
 
Intervention: Transcutaneous electrical nerve stimulation is a safe and effective therapy that has 
been used by physicians and other health professionals for a variety of conditions such as pain and 
muscle rehabilitation26,27. We will use the EV-906 Digital TENS machine (from Everyway Medical 
Instruments Co Ltd, Health Canada License #73631). Two adhesive patch electrodes will be applied 
to one of the patient’s lower limb, and the location used will be based on their treatment 
assignment (active treatment versus sham). The initial treatment will be carried out in the clinic 
under the supervision of the investigating physician, with training provided for the patient on 
proper use of the device by the study nurse. The remaining treatments will be detailed on a 
calendar for the patient, with telephone contact every 2-3 weeks with research staff to assess 
compliance. When undergoing active treatment, patients will have the electrodes applied 
posterior to the medial malleolus, and 5-10 cm above the medial malleolus of the same leg, just 
behind the medial tibial edge. As per previous studies involving transcutaneous posterior tibial 
nerve stimulation25,28,29 and similar to percutaneous tibial nerve stimulation23, we will use the 
bipolar stimulation setting, with a frequency of 10 Hz, 200ms pulse, and the amplitude will be 
titrated up to patient’s maximum nonpainful tolerance (between 0.5-10mA). For patients 
undergoing sham treatment, they will have the patch electrodes placed on the lateral side of the 
lower limb, and told to keep the current setting stable at 1mA. This will prevent any meaningful 
stimulation of the tibial nerve, while still delivering a slight tingling sensation to simulate active 
treatment. 
 
Primary outcome measure: The patient perception of bladder condition (PPBC) is a commonly 
used measure for global response in overactive bladder studies. It is an ordinal scale from 0-5 
(Appendix 3). It is a valid, reliable and responsive single question asking the patient to select the 
degree of problems associated with their bladder condition30. Patients will be categorized as 
responders (score improvement by 2 points between screening visit 1 and end of study visit 3) or 
nonresponders. 
 
Secondary outcome measures: 
1. OAB related quality of life (OAB-q SF) Valid, reliable, and responsive tool for assessing 
symptom bother and OAB related quality of life31. 

 
3 
2. 3-day voiding diary parameters (daily voiding frequency, functional bladder capacity, mean 
voided volume, longest time between voids, nocturia, number of urgency incontinence 
episodes). This is a valid and reliable measure of urinary symptoms32. 
3. Quantification of urinary incontinence with 24hr pad weights. This is stable, reliable and 
responsive measure of the degree of urinary incontinence33,34. 
4. Physician assessment of benefit will be completed based on a standard clinical history at 
study visit 3 (end of study), and graded on a 7 point global response assessment. 
 
Data Analysis and Sample Size 
Analysis of our primary outcome will be an intention to treat analysis (using the chi squared test) 
based on the proportion of patients classified as a responder using the change in the patient 
perception of bladder condition. A secondary analysis, based on a per protocol analysis (for 
efficacy) will be performed for patients who completed at least 80% of the treatment sessions for 
at least 20 min each (determined from patient completed treatment diary, and electronic usage 
log in the TENS device). Secondary endpoints will be analyzed as appropriate using the students t-
test or chi squared test. All data analysis will be carried out using SAS 9.2. 
 
Using previous percutaneous tibial nerve stimulation studies as a guide23, we estimate 20% of  
sham patients and 60% of actively treated patients will be responders. Using the Chi-square test, a 
two-sided alpha of 0.05, and 80% power, 27 patients per group will be required. Our final sample 
size, adjusting for a 10% dropout rate, is 60 (30 per group). Our sample size calculation is based on 
our intention to treat analysis. 
 
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Tai C, Chen M, Shen B, Wang J, Roppolo JR, de Groat WC. Irritation induced bladder overactivity 
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expression in the spinal cord induced by noxious stimulation of the rat bladder. Journal of 
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Finazzi-Agrò E, Petta F, Sciobica F, Pasqualetti P, Musco S, Bove P. Percutaneous tibial nerve 
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doi:10.1016/j.juro.2010.06.113. 
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Vandoninck V, van Balken MR, Finazzi-Agrò E, et al. Percutaneous tibial nerve stimulation in the 
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5 
22. 
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216. doi:10.1016/j.juro.2012.08.085. 
23. 
Peters KM, Carrico DJ, Perez-Marrero RA, et al. Randomized trial of percutaneous tibial nerve 
stimulation versus Sham efficacy in the treatment of overactive bladder syndrome: results from 
the SUmiT trial. J Urol. 2010;183(4):1438-1443. doi:10.1016/j.juro.2009.12.036. 
24. 
van der PAL F, van Balken MR, Heesakkers JPFA, Debruyne FMJ, Bemelmans BLH. Percutaneous 
tibial nerve stimulation in the treatment of refractory overactive bladder syndrome: is 
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410X.2006.06055.x. 
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014-2359-0. 
26. 
Johnson MI. Transcutaneous Electrical Nerve Stimulation (TENS). Oxford University Press; 2014. 
27. 
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28. 
Amarenco G, ISMAEL SS, Even-Schneider A, et al. Urodynamic effect of acute transcutaneous 
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2215. doi:10.1097/01.ju.0000067446.17576.bd. 
29. 
De Seze M, Raibaut P, Gallien P, et al. Transcutaneous posterior tibial nerve stimulation for 
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30. 
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31. 
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32. 
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2000;164(3 Pt 1):698-701. 
33. 
Ryhammer AM, Djurhuus JC, Laurberg S. Pad testing in incontinent women: a review. Int 
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34. 
FLISSER AJ, Figueroa J, Bleustein CB, Panagopoulos G, BLAIVAS JG. Pad test by mail for home 
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doi:10.1002/nau.20023. 
 

 
6 
 
 

 
7 
 
 
 
Appendices 
 
A randomized trial of transcutaneous posterior tibial nerve stimulation for 
refractory overactive bladder patients 
 
Dr Blayne Welk 
 
 
 
 
 
1. Key randomized controlled trials of percutaneous tibial nerve stimulation 
2. Schedule of visits for study patients 
3. Patient perception of bladder condition (PPBC) 
 
 

 
8 
 
Appendix 1. Randomized controlled trials evaluating percutaneous tibial nerve stimulation.  
 
Study 
Sample 
Design 
Intervention/Control 
Outcome 
OrBIT1 
100 adults 
with urinary 
frequency 
>8/day and 
OAB 
Randomized 
controlled trial. 
Intention to treat. 
PTNS (Urgent PC): 0.5-0mA, 
20Hz, unilateral needle 
electrode, weekly 30 minute 
sessions x 12 weeks.  
Control: Tolterodine 4mg OD 
x 90 days 
 
Intervention: 80% global 
response assessment 
moderate or markedly 
improved 
Sham: 55% global 
response assessment 
moderate or markedly 
improved. 
P<0.01 
SUmiT2 
220 adults 
with OAB 
Randomized 
controlled clinical 
trial. Intention to 
treat. 
PTNS (Urgent PC): 0.5-10mA, 
20Hz, unilateral needle 
electrode, weekly 30 minute 
sessions x 12 weeks.  
Control: Sham group with 
identical setup but no active 
electricity. 
Intervention: 55% global 
response assessment 
moderate or markedly 
improved 
Sham: 21% global 
response assessment 
moderate or markedly 
improved. 
P<0.001 
PTNS versus 
placebo3 
35 women 
with 
urodynamic 
DO and wet 
OAB 
Randomized 
controlled trial. 
Intention to treat. 
PTNS (Urgent PC): 0.5-10mA, 
20Hz, unilateral needle 
electrode, 30 minute 
sessions 3x/week x 12 
weeks.  
Control: Sham group with 
identical setup but no active 
electricity. 
Intervention: 71% global 
response assessment 
moderate or markedly 
improved 
Sham: 0% global response 
assessment moderate or 
markedly improved. 
P<0.001 
PTNS vs 
Oxybutynin vs 
Combination for 
OAB4 
70 women 
with OAB 
Randomized 
controlled trial. 
PTNS (Urgent PC): 0.5-0mA, 
10Hz, unilateral needle 
electrode, weekly 30 minute 
sessions x 12 weeks.  
Comparator 1: Oxybutynin 
SR 10mg PO OD x 12 weeks 
Comparator 2: Both PTNS 
and Oxybutynin  x 12 weeks 
Significant reduction 
among all groups, and no 
difference between groups 
based on ICIQ-SF score. 
 
1. 
Peters KM, Macdiarmid SA, Wooldridge LS, et al. Randomized trial of percutaneous tibial nerve stimulation versus 
extended-release tolterodine: results from the overactive bladder innovative therapy trial. J Urol. 2009;182(3):1055–
1061. 
2. 
Peters KM, Carrico DJ, Perez-Marrero RA, et al. Randomized trial of percutaneous tibial nerve stimulation versus Sham 
efficacy in the treatment of overactive bladder syndrome: results from the SUmiT trial. J Urol. 2010;183(4):1438–1443. 
3. 
Finazzi-Agrò E, Petta F, Sciobica F, Pasqualetti P, Musco S, Bove P. Percutaneous tibial nerve stimulation effects on 
detrusor overactivity incontinence are not due to a placebo effect: a randomized, double-blind, placebo controlled trial. 
J Urol. 2010;184(5):2001–2006. 
4. 
Souto SC, Reis LO, Palma T, Palma P, Denardi F. Prospective and randomized comparison of electrical stimulation of the 
posterior tibial nerve versus oxybutynin versus their combination for treatment of women with overactive bladder 
syndrome. World J Urol. 2014;32(1):179–184. 
 
 
 

 
9 
Appendix 2. Study schedule. 
 
STUDY SCHEDULE 
Visit 1 Screening 
Visit 2 
Randomization 
Telephone 
Followup  
Visit 3 End 
of study 
Visit Windows 
1- 4 weeks 
prior to 
Randomization 
Week 0 
Every 2-3 
Weeks 
12-13 Weeks  
Documentation of Consent 
X 
  
  
  
Medical History and Physical Exam 
X 
  
  
  
Inclusion/ Exclusion Criteria Review 
X 
  
  
  
Medication and Health Review 
X 
  
  
X 
Urine Pregnancy Test 
X 
  
  
  
PPBC Questionnaire 
X 
  
X 
(week 6-7 
only) 
X 
OAB-q SF Questionnaire 
X 
  
  
X 
3 day Voiding diary 
Diary Provided 
Completed diary 
returned & new one 
provided for Visit 3 
  
Completed 
diary 
returned  
24hr Urinary Pad test 
Supplies 
Provided with 
instruction 
Pads Returned & 
new ones provided 
for Visit 3 
Pad test 
done 1-7 
days prior to 
visit 3 
Pads 
Returned 
Randomization 
  
X 
  
  
Initial 30 minute treatment session in 
clinic with nurse supervision 
  
X 
  
  
Assessment of treatment masking 
  
  
X  
(week 2-3 
only) 
  
Assessment of compliance, review 
instructions, address any adverse 
events or questions 
  
  
X 
  
Physician assessment of benefit 
  
  
  
X 
 
 
 

 
10
Appendix 3. Patient perception of bladder condition. Scored 0 (no problems) to 5 (severe 
problems). 
 
 
 
 
 
(PPBC) 
Which of the following statements describes your bladder condition best at the 
moment? Please mark ‘‘X’’ in one box only. 
My bladder condition does not cause me any problems at all. 
My bladder condition causes me some very minor problems. 
My bladder condition causes me some minor problems. 
My bladder condition causes me (some) moderate problems. 
My bladder condition causes me severe problems. 
My bladder condition causes me many severe problems.