Wireless, Implantable Tibial Nerve Stimulator System for the Treatment of Refractory Lower Urinary Tract Symptoms in Patients With Multiple Sclerosis (Stimrouter)

Prospective Single Centre Trial of Percutaneous Tibial Nerve Stimulation With the Implantable StimRouter Neuromodulation System for the Treatment of Refractory Lower Urinary Tract Symptoms in Patients With Multiple Sclerosis

Prevalence of lower urinary tract symptoms (LUTS) in patients with multiple sclerosis (MS) increases with disease duration. Current management of urinary clinical symptoms in MS is mainly conservative. Its long-term outcome is often poor because of the progressive disease course and the treatment related side effects. Alternative therapeutic options are botulinum toxin injections, electrical stimulation of dorsal penile/clitoral nerve, and sacral nerve modulation. Posterior tibial nerve stimulation (PTNS) is a second minimally invasive method of electrical stimulation. Multiple benefits may derive from the development and validation of a dedicated protocol of a new self-activated neuromodulation therapy, which may improve therapy compliance/effectiveness, quality of life and social life in MS patients with refractory LUTS. Furthermore, it may contribute to reduce outpatient visits, health costs and work absenteeism.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Device: StimRouter®, Self-activated and self-controlled neuromodulation device (Bioness Inc, CE0086).

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Ticino
    • Lugano, Ticino, Switzerland, 6903
      • Ospedale Regionale di Lugano, Neurocenter of Southern Switzerland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged 18 - 80;
2. Diagnosis of multiple sclerosis according to McDonald [20];
3. Clinical stability over the past 6 months (no relapses and no disability progression, defined as worsening of ≥1 point in the EDSS score if reference EDSS is ≤5.5, and ≥0.5 points if reference EDSS is>5.5);
4. One or more of: urinary frequency greater than 8 times/24 hours, urinary urge incontinence at least 2 episodes in 24 hours on 3-day voiding diary;
5. Urodynamic diagnosis of detrusor over-activity (DOA)and / or detrusor-sphincter dyssynergia (DSD);
6. Previous failure of conservative treatments (challenge over ≥6 months) i.e. lifestyle modification-fluid consumption, behavioral modification, and pharmacological therapy and stable OAB medications for at least 30 days;
7. No pharmacological treatment of overactive bladder (antimuscarinics and beta-3 agonists) for 2 weeks prior to screening;
8. Positive response to ongoing PTNS treatment defined as ≥50% reduction in urinary frequency, and/or ≥50% fewer incontinence episodes, or a return to normal voiding frequency (<8 voids/day), based on retrospective diary review (treatment compliant and non-compliant patients) or PTNS treatment naïve able to sense tibial nerve stimulation (to be tested with TENS exam).
9. Competent sphincter mechanism and normally functioning upper urinary tract;
10. Leg circumference in the range of 20-30 cm at implantation site;
11. No contraindications for surgical intervention (e.g. being immunocompetent, no anticoagulant treatment, no current infection);
12. For female patients: using effective contraceptive methods;
13. Ability to comply with study requirements;
14. Having provided written informed consent.

Exclusion Criteria:

1. Previous participation in another study with any investigational drug or device within the past 90 days;
2. Any metal implant in the area of StimRouter lead implantation site;
3. Anatomical defects that preclude use of the device;
4. Treatment with botulinum toxin injections, urinary incontinence surgery or implantation of artificial graft material, spinal or genitourinary surgery, abdominoperineal resection of the rectum or radical hysterectomy (female)/ prostatectomy (male) within the last 6 months;
5. Previous treatment with sacral neuromodulation;
6. Diagnosis of pelvic pain disorders, stress incontinence, current urinary tract infection, urinary stone and/or urinary tract malignancy; cystocele, enterocele or rectocele of grade 3 or 4;
7. Critical limb ischemia;
8. Previous or current pelvic radiotherapy and/or chemotherapy;
9. Severe uncontrolled diabetes;
10. Being prone to excessive bleeding;
11. Having a pacemaker or implantable defibrillator or other neural stimulation systems;
12. Exposure to diathermy or electrocautery;
13. Clinically significant peripheral neuropathy;
14. Neutropenic or immune compromised;
15. Pelvic radio- and/or chemotherapy;
16. Morbid obesity (BMI >40);
17. Pregnant or lactating women, or women planning a pregnancy during the study, <9 months post-partum;
18. Male: alpha-blocker for benign prostatic hyperplasia;
19. Allergy to local anesthetic or adhesive;
20. Life expectancy <1 year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: With stimulation; Implantation of device electrodes subcutaneous in lower tibia area; stimulation of posterior tibial nerves.	Device: StimRouter®, Self-activated and self-controlled neuromodulation device (Bioness Inc, CE0086).; Regimen 1 (weeks 0-12): one stimulation every 2 days, for a duration of 30 minutes each. Regimen 2 (weeks 12-24): Three stimulation treatments per week, for a duration of 30 minutes each.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in bladder volume	filling volume at the time of the first uninhibited detrusor contraction during cystometry	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cystometric capacity (mL)	Video-urodynamic parameter	6 months
Compliance (ml/cmH20)	Video-urodynamic parameter	6 months
Maximum detrusor pressure (cmH20) during storage phase	Video-urodynamic parameter	6 months
Maximum detrusor pressure (cmH20) during voiding phase	Video-urodynamic parameter	6 months
Voided volume (mL)	Video-urodynamic parameter	6 months
Maximum flow rate (mL/s)	Video-urodynamic parameter	6 months
Post void residual	Video-urodynamic parameter	6 months
Pelvic floor electromyographic activity (normal/detrusor sphincter dyssynergia/non-relaxing pelvic floor)	Video-urodynamic parameter	6 months
Number of voids/day	3-day voiding diary	3, 4.5, 6 months
Volume voided/void	3-day voiding diary	3, 4.5, 6 months
Number of leaks per day	3-day voiding diary	3, 4.5, 6 months
Degree of urgency prior to void	3-day voiding diary	3, 4.5, 6 months
Number of CISC through the day	3-day voiding diary	3, 4.5, 6 months
Residual urine volume	3-day voiding diary	3, 4.5, 6 months
Multiple Sclerosis Quality of Life-54 (MSQOL-54)	54 items, two summary scores: physical health and mental health, range 0-100, a higher score indicates a better quality of life	3, 4.5, 6 months
Over active bladder questionnaire (OAB)	Symptom severity of OAB range 6-36, higher score values indicate greater symptom severity or bother, lower scores indicate minimal symptom severity. Health related quality of life (HRQL) subscales (coping, sleep, and social), range 13-78, Higher scores indicate better HRQL.	3, 4.5, 6 months

Collaborators and Investigators

• Sponsor: Chiara Zecca
• Collaborators: ABREOC

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2020
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: overactive bladder; lower urinary tract symptoms; posterior tibial nerve 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; Multiple Sclerosis, Relapsing-Remitting; Lower Urinary Tract Symptoms
• Other Study ID Numbers: EOC.NEUUR.2002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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