Transcutaneous Tibial Neuro-stimulation to Improve Voiding Dysfunction in Multiple Sclerosis. (NEUROSTIM-SEP1)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Lower Urinary Tract Symptoms
• Intervention / Treatment: Device: PTNS de verum; Device: PTNS placebo

• Study Type: Interventional
• Enrollment (Anticipated): 68
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xavier Biardeau, MD; Phone Number: +33 03.20.44.41.73; Email: xavier.biardeau@chru-lille.fr

Study Locations

• France
  • Lille, France, 59037
    • Recruiting
    • Hop Claude Huriez Chu Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PTNS verum; 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; 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.; Other Names: Peristim Pro (CEFAR-COMPEX®)
Sham Comparator: PTNS placebo; 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; 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; Other Names: Peristim Pro (CEFAR-COMPEX®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Xavier Biardeau, MD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Voiding dysfunction; Bladder-sphincter dyssinergia; Tibial neuro-stimulation
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Urological Manifestations; Multiple Sclerosis; Sclerosis; Lower Urinary Tract Symptoms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Protein Kinase Inhibitors; Cathartics; Emodin
• Other Study ID Numbers: 2018_27; 2018-A03045-50 (Other Identifier: ID-RCB number, ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No