Urinary Bladder, Neurogenic
Conditions
Brief summary
Neurogenic bladder patients may have symptoms of urinary frequency, urgency, urgency incontinence and voiding symptoms due to bladder dysfunction arising from their underlying neurologic condition. Current treatment options are effective for some patients, however many patients are not optimally managed due to modest efficacy or significant side effects. Second line therapies include intravesical onabotulinum toxin, however it is associated with a risk of urinary retention, and patients with neurologic disorders often are unable to perform self catheterize due to physical limitations. Sacral neuromodulation is associated with an undesirably high cost and potential complications in this population. The use of transcutaneous tibial nerve stimulation is an alternative form of neuromodulation, and it may have some potential benefits over percutaneous tibial nerve stimulation. While some preliminary studies have suggested it may be effective, there are no high quality randomized trials. This proposal is a 3 month, randomized, sham-controlled, clinical trial to evaluate the short term clinical efficacy of at home transcutaneous tibial nerve stimulation. Valid and reliable patient reported outcome measures, and objective measures of incontinence have been included as outcomes.
Interventions
DEVICEEV-906 Digital Transcutaneous electrical nerve stimulation (TENS) machine
Percutaneous patch electrodes are used to deliver low level electrical currents.
Sponsors
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. \>18 years of age, with a clinical condition associated with neurogenic bladder dysfunction (multiple sclerosis, Parkinson's disease, stroke, dementia, cerebral palsy, spinal cord injury)(27). 2. Failure of behavioral measures and/or pharmacologic therapy to adequately control neurogenic bladder symptoms.
Exclusion criteria
1. Current or previous percutaneous/transcutaneous tibial nerve stimulation or sacral neuromodulation therapy 2. Stress predominant urinary incontinence 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. Metallic implant within the lower limb
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Perception of Bladder Condition Questionnaire | 3 months | Patient perception of bladder condition (PPBC) question. It is scored from 0 (My bladder condition does not cause me any problems at all) to 5 (My bladder condition causes me many severe problems). Higher numbers are worse outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurogenic Bladder Symptom Score (NBSS) Questionnaire | 3 months | The NBSS is a patient reported symptom score covering three domains: incontinence, storage/voiding, and consequences. It is scored from 0 to 72, and a higher score is worse outcome. |
| Qualiveen-Short Form Questionnaire | 3 months | Patient reported questionnaire that measures quality of life among neurogenic bladder patients. Score ranges from 0 to 32. A higher score is worse. |
| 3-day Voiding Diary | 3 months | Daily urinary frequency as recorded by the patient over 3 days. Summarised as an average daily frequency. |
| 24hr Incontinence Pad Weights | 3 months | — |
| Physician Assessment of Patient Benefit (Global Response Scale) | 3 months | Completed by physicians based on their assessment after discussion with the patient as to the amount of benefit they received. Reported on a scale of 0 (no benefit) to 7 (substantial benefit) |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sham Tibial Nerve Stimulation Use of peripheral nerve stimulator in a location that will not actively stimulate the tibial nerve.
EV-906 Digital Transcutaneous electrical nerve stimulation (TENS) machine: Percutaneous patch electrodes are used to deliver low level electrical currents. | 14 |
| Tibial Nerve Stimulation Transcutaneous peripheral nerve stimulator in a location that will actively stimulate the tibial nerve.
EV-906 Digital Transcutaneous electrical nerve stimulation (TENS) machine: Percutaneous patch electrodes are used to deliver low level electrical currents. | 16 |
| Total | 30 |
Baseline characteristics
| Characteristic | Tibial Nerve Stimulation | Total | Sham Tibial Nerve Stimulation |
|---|---|---|---|
| Age, Continuous | 60 years | 56 years | 53 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants | 30 Participants | 14 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 16 |
| other Total, other adverse events | 0 / 14 | 0 / 16 |
| serious Total, serious adverse events | 0 / 14 | 0 / 16 |
Outcome results
Primary
Patient Perception of Bladder Condition Questionnaire
Patient perception of bladder condition (PPBC) question. It is scored from 0 (My bladder condition does not cause me any problems at all) to 5 (My bladder condition causes me many severe problems). Higher numbers are worse outcomes.
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sham Tibial Nerve Stimulation | Patient Perception of Bladder Condition Questionnaire | 3 units on a scale |
| Tibial Nerve Stimulation | Patient Perception of Bladder Condition Questionnaire | 3 units on a scale |
Secondary
24hr Incontinence Pad Weights
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sham Tibial Nerve Stimulation | 24hr Incontinence Pad Weights | 364 grams |
| Tibial Nerve Stimulation | 24hr Incontinence Pad Weights | 362 grams |
Secondary
3-day Voiding Diary
Daily urinary frequency as recorded by the patient over 3 days. Summarised as an average daily frequency.
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sham Tibial Nerve Stimulation | 3-day Voiding Diary | 9 voids per 24 hrs |
| Tibial Nerve Stimulation | 3-day Voiding Diary | 9 voids per 24 hrs |
Secondary
Neurogenic Bladder Symptom Score (NBSS) Questionnaire
The NBSS is a patient reported symptom score covering three domains: incontinence, storage/voiding, and consequences. It is scored from 0 to 72, and a higher score is worse outcome.
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sham Tibial Nerve Stimulation | Neurogenic Bladder Symptom Score (NBSS) Questionnaire | 33 Units on a scale |
| Tibial Nerve Stimulation | Neurogenic Bladder Symptom Score (NBSS) Questionnaire | 29 Units on a scale |
Secondary
Physician Assessment of Patient Benefit (Global Response Scale)
Completed by physicians based on their assessment after discussion with the patient as to the amount of benefit they received. Reported on a scale of 0 (no benefit) to 7 (substantial benefit)
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sham Tibial Nerve Stimulation | Physician Assessment of Patient Benefit (Global Response Scale) | 3 units on a scale |
| Tibial Nerve Stimulation | Physician Assessment of Patient Benefit (Global Response Scale) | 3 units on a scale |
Secondary
Qualiveen-Short Form Questionnaire
Patient reported questionnaire that measures quality of life among neurogenic bladder patients. Score ranges from 0 to 32. A higher score is worse.
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sham Tibial Nerve Stimulation | Qualiveen-Short Form Questionnaire | 27 units on a scale |
| Tibial Nerve Stimulation | Qualiveen-Short Form Questionnaire | 27 units on a scale |