Non-invasive Nerve Stimulation for Inhibition of Bladder Incontinence in Spinal Cord Injured Subjects.
Phase: NA
Conditions: Spinal Cord Injuries
Sponsor: Taipei Medical University

 
TMU-Joint Institutional Review Board 
 
 
Title: 
Non-invasive Nerve Stimulation for Inhibition of Bladder 
Incontinence in Spinal Cord Injured Subjects. 
 
NCT number: NCT03877432 
Date: 2020/10/29 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Protocol and Statistical Analysis Plan 
➢ Study Aim 
Neurogenic bladder is among the most common complications associated with spinal 
cord injury, multiple sclerosis and stroke. Neurogenic bladder frequently leads to urological 
complications, such as incontinence, urinary tract infection, renal damage and subsequent 
renal dialysis or transplantation. “Turning off” the bladder (i.e. reducing reflex voiding and 
spasticity of the bladder, decreasing bladder pressures and increasing bladder capacity) has the 
potential to reduce the number and severity of these complications. Current methods for 
improving bladder function in persons with neurogenic bladder, including pharmacologic and 
surgical interventions, are incompletely effective. 
The objective of this work is to decrease bladder hyper-reflexia using non-invasive 
cutaneous nerve stimulation of the S2-S4 dermatome nerve. To examine outcomes following 
SCI, investigators will test dermatome ES with individuals using intermittent catheterization to 
estimate the clinical impact on bladder capacity and continence. 
 
➢ Inclusion Criteria 
 
Uprasacral SCI 
 
Neurologically stable 
 
Skeletally mature, over 18 years of age 
 
At least six (6) months post SCI 
 
Able to understand and comply with study requirements 
 
Able to understand and give informed consent 
 
➢ Exclusion Criteria 
 
Active sepsis 
 
Open wound or pressure sores on cutaneous area 
 
Significant trauma, erosion or stricture of the urethra 
 
Pregnancy 
 
Individuals who can not speak 
 
➢ Study Protocol 
Anticholinergic medications may mask the effects of dermatome ES. If subjects take 

anticholinergics (medicines to make participants’ bladder relax, such as Ditropan, Oxybutynin, 
Detrol LA, Detrol, Tolterodine Tartate, Tofranil, Imipramine, Urimax, Xanodine, Enablex, 
Darifenain) participants will be asked to stop them for two weeks before the study. This may 
make it more likely that participants’ bladder will leak and participants may need to use a pad 
or wear a catheter and leg bag to collect this leakage. 
Urologic data collection will occur in the urodynamic laboratory for a single trial for ~2 
hours. A dual-lumen Foley catheter will be inserted into the bladder via the urethra and the 
bladder will be emptied (volume recorded). One lumen of the catheter will be connected to a 
pressure transducer and amplifier to record bladder pressure, and the second lumen will be 
used to control bladder volume by filling and emptying with sterile saline. A balloon catheter 
inserted in the rectum will be used to determine detrusor pressure by subtracting rectal from 
vesical pressure. Surface electromyogram (EMG) electrodes will be applied to the anal 
sphincter to monitor pelvic floor activity. Infused volumes will be measured both via a force 
transducer and infusion pump. Signals will be monitored on an urodynamic system. Besides, 
two surface electrodes (1 cm x 1 cm) will be placed on the approximately cutaneous area of 
S2-S4 dermatome. Investigators expect to obtain bilateral area stimulation. The electrodes will 
be connected to the stimulator. 
Serial cystometrograms will be conducted by filling the bladder with saline and recording 
the volume and pressure in the bladder. A total of 8 serial cystometrograms will be performed: 
2 control fills, followed by 4 fills with stimulation, followed by 2 control fills. An initial 
cystometrogram will be used to verify bladder inhibition: the bladder will be filled until 
reflexive bladder contractions are elicited and electrical stimulation applied after the onset of a 
bladder contraction. For serial cystometrograms, stimulation will be initiated 30 seconds prior 
to, and stopped 30 seconds after, the cystometrogram. When bladder filling reaches the 
threshold volume at which reflex bladder contraction occurs (a bladder pressure increase 
greater than 35 cmH2O sustained for >10 s or any bladder voiding), filling will be stopped. At 
the end of each cystometrogram, the bladder will be emptied and the volume added to any  
voided volume to determine total bladder volume. 
 
➢ Potential Side-effects and Handling Methods 
1. 
Elevated blood pressure or Autonomic Dysreflexia (AD) 
There is a risk in subjects with spinal cord injury of elevation of blood pressure when 
the bladder is distended or contracting. This is due to autonomic dysreflexia and the risk is 

dependent on the neurological level of spinal cord injury, being of relatively little 
significance with lesions below T6 but of increasing significance with higher lesions, and is 
well-known in clinical urodynamic testing. The elevation of blood pressure is occasionally 
asymptomatic but is usually associated with symptoms such as flushing of the face, nasal 
congestion, and headache and is well-known to most subjects with spinal cord injury. If 
ntreated it can result in stroke or death. This risk will be minimized by ensuring that 
subjects are familiar with the condition and its prevention and management and if 
necessary providing them with the standard medications used for its management. During 
urodynamic testing in this study the risk will be minimized by monitoring blood pressure 
with automatic measurement at least every five minutes, by stopping bladder filling and 
emptying the bladder in the event of substantial rises in blood pressure, and by utilizing 
the standard autonomic dysreflexia protocol in place in the SCI outpatient clinic. 
2. 
Urinary tract infection 
There is a risk of approximately less than 10% that a subject with SCI will develop a 
urinary tract infection (UTI) following urodynamics in this study. This risk will be minimized 
by performing catheterization with sterile technique. If the subject experiences signs or 
symptoms of a UTI (such as blood in the urine, frequency, urgency, increased spasms, fever, 
chills, and/or pain in the lower back) after the study, they will be instructed to contact a 
member of the study team. The subject will be examined and treated, if necessary, with 
the appropriate antibiotic. 
3. 
Urethral trauma 
There is a small risk, which investigators estimate at approximately 2%, that a subject 
will experience mild trauma to the urethra as a result of catheterization for this study. 
Such trauma might result in a small amount of bleeding from the surface of the urethra, 
similar to that seen from the gums on vigorous tooth-brushing. This risk will be minimized 
by lubricating the catheter with sterile water-soluble gel and by careful catheterization 
technique. Many individuals catheterize themselves multiple times per day and therefore 
the risk in these subjects is not significant. 
4. 
Tissue burn 
There is a very small risk that skin electrodes for electrical stimulation or recording 
could cause a tissue burn. This risk is very low because of the level of electrical stimulation 
and safety testing of the equipment. The safety of the complete electrical set up will be 
tested and documented before any testing is done. Periodic biomedical safety checks will 

be performed for the intended use of all equipment used during these studies. 
5. 
Skin irritation 
There is a slight risk of skin irritation from the electrodes applied to the skin for 
electrical stimulation or from the gel used to assist in conducting the electricity. This will 
be minimized by using electrodes that are not known to be allergenic, and by using gel 
that is commonly used for other types of electrical stimulation and recording. The 
electrodes applied to the skin surface do not come into contact with the saline solution or 
urine. 
6. 
Exposure to uncomfortable electrical stimulation 
Subjects with incomplete SCI may be exposed, during acute experiments, to 
stimulation levels that are uncomfortable. This risk is small and manageable because 
stimulus amplitude will be increased slowly and discontinued if desired. Previous 
dermatome studies in non-SCI women to determine maximum tolerable stimulation levels 
have been conducted, therefore investigators do not expect tolerance to stimulation to be 
a limitation. 
7. 
Incontinence 
There is a risk of increased incontinence due to increased bladder capacity in 
patients who are asked to discontinue their usual anticholinergic medication 2 weeks 
before the study and for the duration of the study. This risk will be managed by describing 
it to the subjects and by offering them alternative methods of managing incontinence 
during this period, such as a condom and leg-bag system, pads, diapers, or catheterization. 
 
➢ Statistical Analysis Plan 
Investigators will use repeated measures ANOVA to determine the effects of dermatome 
stimulation on each outcome measure. Investigators will include subject as a factor in our 
analysis and consider starting levels as potential covariates. The outcome measures will be 
plotted as a function of day number throughout the trial to look for trends including increases 
or decreases in stimulation effectiveness. In addition, examination of baseline characteristics 
such as age, SCI location, etc. against the outcome effects might shed some light on other 
possible covariates to consider in future studies.