Clinical trial NCT04567264: Wireless, Implantable Tibial Nerve Stimulator System for the Treatment of Refractory Lower Urinary Tract Symptoms in Patients With Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: overactive bladder
posterior tibial nerve stimulation
lower urinary tract symptoms
Lead sponsor: Ente Ospedaliero Cantonale, Bellinzona
Sponsor class: OTHER
Collaborators: name: ABREOC
First posted: 2020-09-28
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, interventional, single center
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in bladder volume
timeFrame: 6 months
Secondary outcomes:
measure: Cystometric capacity (mL)
timeFrame: 6 months
measure: Compliance (ml/cmH20)
timeFrame: 6 months
measure: Maximum detrusor pressure (cmH20) during storage phase
timeFrame: 6 months
measure: Maximum detrusor pressure (cmH20) during voiding phase
timeFrame: 6 months
measure: Voided volume (mL)
timeFrame: 6 months
measure: Maximum flow rate (mL/s)
timeFrame: 6 months
measure: Post void residual
timeFrame: 6 months
measure: Pelvic floor electromyographic activity (normal/detrusor sphincter dyssynergia/non-relaxing pelvic floor)
timeFrame: 6 months
measure: Number of voids/day
timeFrame: 3, 4.5, 6 months
measure: Volume voided/void
timeFrame: 3, 4.5, 6 months
measure: Number of leaks per day
timeFrame: 3, 4.5, 6 months
measure: Degree of urgency prior to void
timeFrame: 3, 4.5, 6 months
measure: Number of CISC through the day
timeFrame: 3, 4.5, 6 months
measure: Residual urine volume
timeFrame: 3, 4.5, 6 months
measure: Multiple Sclerosis Quality of Life-54 (MSQOL-54)
timeFrame: 3, 4.5, 6 months
measure: Over active bladder questionnaire (OAB)
timeFrame: 3, 4.5, 6 months
Other outcomes:
Locations:
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano, Neurocenter of Southern Switzerland
state: Ticino
Study officials:
References: