wireless, implantable tibial nerve stimulator system for the treatment of refractory lower urinary tract symptoms in patients with multiple sclerosis

Conditions: Multiple Sclerosis, Relapsing-Remitting

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.

Keywords: overactive bladder posterior tibial nerve stimulation lower urinary tract symptoms