Transcutaneous Tibial Nerve Stimulation for Spinal Cord Injury Neurogenic Bladder

Study Overview
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Brief Summary
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The purpose of this study is to determine if electric stimulation to the leg, called transcutaneous tibial nerve stimulation (TTNS), can improve bladder outcomes in acute spinal cord injury.

Detailed Description
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The purpose of this study is to see how well TTNS works at preventing incontinence in people with paraplegia from SCI that perform intermittent catheterization to empty their bladder. This study will compare the effectiveness of TTNS at 2 doses, fixed-dose and variable-dose. It will also evaluate the frequency of use, 2 days weekly compared to 5 days weekly. Based on our pilot trials, tibial nerve stimulation protocols use submotor current intensity with a duration of 200 µs and a frequency of 20Hz. The experimental group will use a submotor variable dose. The fixed-dose group will use submotor at current intensity at 1mA and designated as fixed-dose. TTNS will be used 5 days weekly, per our pilot trial. At 4-months post-SCI, the subject will be instructed to switch to 2x daily if he or she was randomized into the variable dose group of 2 days weekly and thus continue to doing so for the remainder of study participation. Because there is support in the literature for reduced doses of tibial nerve stimulation required for maintenance (1-3x weekly), the RCT includes this frequency comparison arm. All subjects will continue for 1-year post-SCI. Additionally, we are collecting surveys to help identify characteristics of people (resilience and confidence) and adherence to medication and TTNS use throughout the study.

Official Title
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Transcutaneous Tibial Nerve Stimulation for Spinal Cord Injury Neurogenic Bladder

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Device: Variable-dose TTNS Protocol 5 x week
* Device: Fixed-dose TTNS Protocol
* Device: Variable-dose TTNS Protocol 2 x week


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years old Traumatic or non-traumatic SCI Admitted to inpatient rehabilitation within 6 weeks T9 level of injury and above who are at greatest risk of morbid NGB Regionally located to allow follow-up English or Spanish speaking Exclusion Criteria: History of genitourinary diagnoses (i.e. prostate hypertrophy, overactive bladder, cancer, etc.) History of central nervous system disorder (i.e. prior SCI, stroke, brain injury, Parkinson's disease, MS, etc.) History of peripheral neuropathy pre-SCI symptoms of peripheral neuropathy (numbness and/or tingling in feet, sharp/jabbing/burning pain in feet, sensitivity to touch, lack of coordination, muscle weakness, etc.) Pregnancy Known injury to the lumbosacral spinal cord or plexus, or pelvis with associated neuropathy concern for tibial nerve pathway injury absence of toe flexion or autonomic dysreflexia during electric stimulation test Potential for progressive SCI including neurodegenerative SCI, ALS, cancer myelopathy, Multiple sclerosis, transverse myelitis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: A prospective, double-blinded, randomized trial.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Variable-dose TTNS Protocol 5 x week<br>TTNS protocol: Electrodes 2 inch by 2 inch will be placed according to anatomic landmarks, with the negative electrode behind the internal malleolus and the positive electrode 10cm superior to the negative electrode, verified with rhythmic flexion of the toes secondary to stimulation of the flexor digitorum and hallicus brevis. The intensity level will be set to the amperage immediately under the threshold for motor contraction. If there is no contraction seen, patients will be excluded. In addition, if the patient perceives pain, the intensity will be lowered until comfortable. Stimulation frequency of 20 Hz and pulse width of 200ms in continuous mode will be used. All participants will be instructed to use the device for 30 minutes, 5 days per week for the first 4 months post-sci. | Device: Variable-dose TTNS Protocol 5 x week<br>* Electrodes 2 inch by 2 inch will be placed according to anatomic landmarks, with the negative electrode behind the internal malleolus and the positive electrode 10cm superior to the negative electrode, verified with rhythmic flexion of the toes secondary to stimulation of the flexor digitorum and hallicus brevis. The intensity level will be set to the amperage immediately under the threshold for motor contraction. If there is no contraction seen, patients will be excluded. In addition, if the patient perceives pain, the intensity will be lowered until comfortable. Stimulation frequency of 20 Hz and pulse width of 200ms in continuous mode will be used.<br>|
| Active Comparator: Fixed-dose TTNS protocol<br>Fixed-dose protocol: Toe flexion will be attempted, as in the TTNS protocol. Then the stimulation will be reduced to 1 mA for 30 minutes. Both variable-dose TTNS and fixed-dose TTNS protocol participants will be instructed to use the device for 30 minutes, 5 days per week. | Device: Fixed-dose TTNS Protocol<br>* Toe flexion will be attempted, as in the TTNS protocol. Then the stimulation will be reduced to 1 mA for 30 minutes. This will continue at 5x weekly until 1-year post-injury.<br>|
| Active Comparator: Variable-dose TTNS Protocol 2 x week<br>At the 4 month CMG, subjects initially randomized into the variable dose protocol of 2 x weekly will start doing so for the remainder of the study. | Device: Variable-dose TTNS Protocol 2 x week<br>* At the 4 month CMG, subjects initially randomized into the variable dose protocol of 2 x weekly will start doing so for the remainder of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maintained bladder capacity as assessed by the Urodynamics study measured in ml | we expect bladder capacity to be maintained in those with effective TTNS | Baseline | 
| Maintained bladder capacity as assessed by the Urodynamics study measured in ml | we expect bladder capacity to be maintained in those with effective TTNS | 4 months post SCI | 
| Prolonged sensation with bladder filling as assessed by the Urodynamics study measured in ml | Evidence of TTNS mechanism expected in those with effective TTNS | Baseline | 
| Prolonged sensation with bladder filling as assessed by the Urodynamics study measured in ml | Evidence of TTNS mechanism expected in those with effective TTNS | 4 months post SCI | 
| Prolonged sensation with bladder filling as assessed by the Urodynamics study measured in ml | Evidence of TTNS mechanism expected in those with effective TTNS | 1 year post SCI | 
| Change in bladder pathology from baseline presence of detrusor overactivity and DSD as assessed by the urodynamics study at 4 months. | Reduced bladder pathology (presence of detrusor overactivity and DSD) in those with effective bladder neuromodulation based on change in urodynamic studies at baseline and 4-months | Baseline, 4 months | 
| Change in bladder pathology from 4 month presence of detrusor overactivity and DSD as assessed by the urodynamics study at 1 year post SCI. | Reduced bladder pathology (presence of detrusor overactivity and DSD) in those with effective bladder neuromodulation based on the change in urodynamic studies at 4 months and 1-year | 4 months and 1 year post SCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of improved quality of life in those with effective bladder neuromodulation based on Incontinence Quality of Life (I-QOL) survey | Comparing I-QOL upon discharge from rehabilitation, 4-months post-injury and 1-year post-injury using incontinence QOL (I-QOL) survey, between and within both arms of the study | At discharge which could be up to 4 week from admission, 4-months post injury and at 1 year post injury. | 
| Evidence of improved quality of life in those with effective bladder neuromodulation based on Neurogenic Bladder Symptom Score (NBSS) | Changes in Neurogenic Bladder Symptom Scores. The total score can range from 0 (no symptoms at all) to 74 (maximum symptoms) where a lower score indicates a better outcome. | Prior to discharge which could be up to 4 weeks from admission, monthly until 1 year post injury. | 
| Evidence of improved quality of life in those with effective bladder neuromodulation based on frequency of catheterization and voiding volumes | Maintaining frequency of catheterization (count per day) and volumes per void (ml per collection) | 2 days at the end of each month for 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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electric stimulation, SCI, spinal cord injury, neurogenic bladder