Transcutaneous Tibial Neuro-stimulation to Improve Voiding Dysfunction in Multiple Sclerosis.

Study Overview
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Brief Summary
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The present trial is designed to assess the efficacy and safety of transcutaneous tibial neuro-stimulation (TTNS) in improving bladder emptying in multiple sclerosis (MS) patients. Patients presenting with MS and performing clean intermittent self-catheterization (CISC) to empty the bladder in the context of voiding dysfunction, will be eligible. Included patients will be randomly assigned to two distinct arms PTNS de verum : patients will be treated with transcutaneous tibial neuro-stimulation at a rate of one session of 30 consecutive minutes daily for a period of 12 weeks. PTNS placebo : Patients will be treated with placebo (i.e. no current) transcutaneous tibial neuro-stimulation for 30 consecutive minutes daily for a period of 12 weeks (same treatment regimen as the experimental group). Efficacy in improving voiding dysfunction will be assessed 12 weeks after randomization using the BVE ratio (Bladder Voiding Efficiency) = Ratio of urine volume / total bladder volume.

Official Title
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Efficacy and Safety of Transcutaneous Tibial Neuro-stimulation to Improve Voiding Dysfunction in Multiple Sclerosis Patients.

Conditions
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Multiple Sclerosis, Lower Urinary Tract Symptoms

Intervention / Treatment
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* Device: PTNS de verum
* Device: PTNS placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with a diagnosis of multiple sclerosis Patient with bladder-sphincter dyssinergia Patient using clean intermittent self-catheterization as exclusive bladder management Patient who has given written consent Socially insured patient Patient willing to comply with all study procedures and study duration Exclusion Criteria: Patient with other associated neurological pathology Patient with an Expanded Disability Status Scale (EDSS) score ≥ 6 Patient with recurrent urinary tract infections (> 3 episodes / year) Patient with uncontrolled overactive bladder Patient with uncontrolled detrusor hyperactivity Patient with a bladder compliance disorder Patient with tibial neuro-stimulation in the last 3 months Patient treated with a sacral neuro-modulation Patient who has received an intradermal injection of botulinum toxin A within the last 9 -months Patient who received alpha-blocker treatment within the last month Patient with benign prostatic hypertrophy (prostate volume > 40 cc) - Last ultrasound scan < 6 months. Patient with one or more bladder diverticulum(s) Patient with unilateral or bilateral renal Patient with unilateral or bilateral vesico-ureteral reflux Patient with impaired renal function (GFR according to CKD-EPI < 60 ml/min/1.73m2) Patient with a metallic prosthesis on the lower limb Patient with a Pacemaker Pregnant patient

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTNS verum<br>Patients will be treated with transcutaneous tibial neuro-stimulation with one 30-minute session daily for a period of 12 weeks. | Device: PTNS de verum<br>* The device will be set to program P-4: Frequency 20Htz, Pulse duration = 200 µs. The amplitude (Volt) will be adjusted by the patient according to the feeling.<br>* Other names: Peristim Pro (CEFAR-COMPEX®);|
| Sham Comparator: PTNS placebo<br>Patients will be treated with placebo (i.e. no current) transcutaneous tibial neuro-stimulation for 30 consecutive minutes daily for 12 weeks (same treatment regimen as the experimental group). | Device: PTNS placebo<br>* The device will be set to program P-4: Frequency 20Htz, Pulse duration = 200 µs. A resistor will be incorporated in the device to block the passage of electric current<br>* Other names: Peristim Pro (CEFAR-COMPEX®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BVE ratio (Bladder Voiding Efficiency) = Ratio of urine volume / total bladder volume | BVE will be measured during the multi-channel urodynamic study | At 12 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal flow rate (mL/s) on multi-channel urodynamic study | Maximal flow rate will be measured during the multi-channel urodynamic study | At baseline, At 12 weeks after randomization | 
| Post-void residual volume (mL) on multi-channel urodynamic study | Post-void residual volume will be measured during the multi-channel urodynamic study | At 12 weeks after randomization | 
| Maximal detrusor pressure during micturition (cmH2O) on multi-channel urodynamic study | Maximal detrusor pressure during micturition will be measured during the multi-channel urodynamic study | At 12 weeks after randomization | 
| Mean voided volume (mL) on a three-day ambulatory measure | Mean voided volume will be measured using an ambulatory flowmeter (Homeflow®) during three consecutive days | At 12 weeks after randomization | 
| Mean maximal flow rate (mL/s) on a three-day ambulatory measure | Mean maximal flow rate will be measured using an ambulatory flowmeter (Homeflow®) during three consecutive days | At 12 weeks after randomization | 
| Mean post-void residual volume (mL) on a three-day ambulatory measure | Mean post-void residual volume will be measured using an ambulatory flowmeter (Homeflow®) during three consecutive days. | At 12 weeks after randomization | 
| Frequency of patients who were able to stop clean intermittent self-catheterization (PVR < 100 mL) | Mean post-void residual volume will be measured using an ambulatory flowmeter (Homeflow®) during three consecutive days | At 12 weeks after randomization | 
| Urinary symptoms self-reported questionnaire (USP) | USP : Urinary Symptom Profile | At 12 weeks after randomization | 
| Quality of life self-reported questionnaire (Qualiveen) | Qualiveen | At 12 weeks after randomization | 
| Difficulty to perform CISC self-reported questionnaire (ICDQ) | ICDQ : Intermittent Catheterization Difficulty Questionnaire | At 12 weeks after randomization | 
| Digestive symptoms self-reported questionnaire (NBD) | NBD : Neurogenic Bowel Dysfunction | At 12 weeks after randomization | 
| Digestive symptoms self-reported questionnaire (Wexner) | Wexner questionnaire | At 12 weeks after randomization | 
| Sexual symptoms self-reported questionnaire (FSFI) | FSFI (female) : Female Sexual Function Index | At 12 weeks after randomization | 
| Sexual symptoms self-reported questionnaire ( MSHQ) | MSHQ (male) : Male Sexual Health Questionnaire | At 12 weeks after randomization | 
| Frequency of patients with detrusor overactivity on multi-channel urodynamic study | Detrusor overactivity will be objectify during the multi-channel urodynamic study | At 12 weeks after randomization | 
| Filling volume (mL) at first detrusor unhibited contraction on multi-channel urodynamic study - If detrusor overactivity. | Filling volume at first detrusor unhibited contraction will be measured during the multi-channel urodynamic study. | At 12 weeks after randomization | 
| Maximal detrusor pressure (cmH2O) on multi-channel urodynamic study - If detrusor overactivity. | Maximal detrusor pressure will be measured during the multi-channel urodynamic study | At 12 weeks after randomization | 
| Maximal cystomanometric capacity (cmH2O) on multi-channel urodynamic study | Maximal cystomanometric capacity will be measured during the multi-channel urodynamic study | At 12 weeks after randomization | 
| Frequency of adverse events occurring during the 12-week follow-up | Adverse events will be exhaustively listed | Measured 12 weeks after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis, Voiding dysfunction, Bladder-sphincter dyssinergia, Tibial neuro-stimulation