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

Sponsor

Chiara Zecca (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04567264

Collaborator

ABREOC (Other)

Enrollment

Location

Arm

22.1

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis, Relapsing-Remitting	Device: StimRouter®, Self-activated and self-controlled neuromodulation device (Bioness Inc, CE0086).	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Prospective, interventional, single centerProspective, interventional, single center

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 26, 2020

Anticipated Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Jun 30, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Change in bladder volume [6 months]
filling volume at the time of the first uninhibited detrusor contraction during cystometry

Secondary Outcome Measures

Cystometric capacity (mL) [6 months]
Video-urodynamic parameter
Compliance (ml/cmH20) [6 months]
Video-urodynamic parameter
Maximum detrusor pressure (cmH20) during storage phase [6 months]
Video-urodynamic parameter
Maximum detrusor pressure (cmH20) during voiding phase [6 months]
Video-urodynamic parameter
Voided volume (mL) [6 months]
Video-urodynamic parameter
Maximum flow rate (mL/s) [6 months]
Video-urodynamic parameter
Post void residual [6 months]
Video-urodynamic parameter
Pelvic floor electromyographic activity (normal/detrusor sphincter dyssynergia/non-relaxing pelvic floor) [6 months]
Video-urodynamic parameter
Number of voids/day [3, 4.5, 6 months]
3-day voiding diary
Volume voided/void [3, 4.5, 6 months]
3-day voiding diary
Number of leaks per day [3, 4.5, 6 months]
3-day voiding diary
Degree of urgency prior to void [3, 4.5, 6 months]
3-day voiding diary
Number of CISC through the day [3, 4.5, 6 months]
3-day voiding diary
Residual urine volume [3, 4.5, 6 months]
3-day voiding diary
Multiple Sclerosis Quality of Life-54 (MSQOL-54) [3, 4.5, 6 months]
54 items, two summary scores: physical health and mental health, range 0-100, a higher score indicates a better quality of life
Over active bladder questionnaire (OAB) [3, 4.5, 6 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female aged 18 - 80;
Diagnosis of multiple sclerosis according to McDonald [20];
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);
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;
Urodynamic diagnosis of detrusor over-activity (DOA)and / or detrusor-sphincter dyssynergia (DSD);
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;
No pharmacological treatment of overactive bladder (antimuscarinics and beta-3 agonists) for 2 weeks prior to screening;
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).
Competent sphincter mechanism and normally functioning upper urinary tract;
Leg circumference in the range of 20-30 cm at implantation site;
No contraindications for surgical intervention (e.g. being immunocompetent, no anticoagulant treatment, no current infection);
For female patients: using effective contraceptive methods;
Ability to comply with study requirements;
Having provided written informed consent.

Exclusion Criteria:

Previous participation in another study with any investigational drug or device within the past 90 days;
Any metal implant in the area of StimRouter lead implantation site;
Anatomical defects that preclude use of the device;
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;
Previous treatment with sacral neuromodulation;
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;
Critical limb ischemia;
Previous or current pelvic radiotherapy and/or chemotherapy;
Severe uncontrolled diabetes;
Being prone to excessive bleeding;
Having a pacemaker or implantable defibrillator or other neural stimulation systems;
Exposure to diathermy or electrocautery;
Clinically significant peripheral neuropathy;
Neutropenic or immune compromised;
Pelvic radio- and/or chemotherapy;
Morbid obesity (BMI >40);
Pregnant or lactating women, or women planning a pregnancy during the study, <9 months post-partum;
Male: alpha-blocker for benign prostatic hyperplasia;
Allergy to local anesthetic or adhesive;
Life expectancy <1 year.