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

Not Applicable

Completed

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

• Registration Number: NCT04567264
• Lead Sponsor: Chiara Zecca

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-08-26
• Study First Submitted: 2020-09-23
• Study First Submitted QC: 2020-09-23
• Study First Posted: 2020-09-28
• Primary Completion: 2022-06-30
• Study Completion: 2022-06-30
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-06
• Last Update Posted: 2023-09-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
With stimulation	StimRouter®, Self-activated and self-controlled neuromodulation device (Bioness Inc, CE0086).	Implantation of device electrodes subcutaneous in lower tibia area; stimulation of posterior tibial nerves.

Primary Outcome Measures

Name	Time	Method
Change in bladder volume	6 months	filling volume at the time of the first uninhibited detrusor contraction during cystometry

Secondary Outcome Measures

Name	Time	Method
Number of CISC through the day	3, 4.5, 6 months	3-day voiding diary
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
Degree of urgency prior to void	3, 4.5, 6 months	3-day voiding diary
Residual urine volume	3, 4.5, 6 months	3-day voiding diary
Number of leaks per day	3, 4.5, 6 months	3-day voiding diary
Pelvic floor electromyographic activity (normal/detrusor sphincter dyssynergia/non-relaxing pelvic floor)	6 months	Video-urodynamic parameter
Compliance (ml/cmH20)	6 months	Video-urodynamic parameter
Voided volume (mL)	6 months	Video-urodynamic parameter
Maximum flow rate (mL/s)	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
Post void residual	6 months	Video-urodynamic parameter
Cystometric capacity (mL)	6 months	Video-urodynamic parameter
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.

Trial Locations

Locations (1)

Ospedale Regionale di Lugano, Neurocenter of Southern Switzerland; 🇨🇭 Lugano, Ticino, Switzerland