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

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.