Multiple Sclerosis, Relapsing-Remitting
Conditions
Keywords
overactive bladder, posterior tibial nerve stimulation, lower urinary tract symptoms
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.
Interventions
DEVICEStimRouter®, 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.
Sponsors
ABREOC
Chiara Zecca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, interventional, single center
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in bladder volume | 6 months | filling volume at the time of the first uninhibited detrusor contraction during cystometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Cystometric capacity (mL) | 6 months | Video-urodynamic parameter |
| 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. |
| Number of voids/day | 3, 4.5, 6 months | 3-day voiding diary |
Countries
Switzerland
Outcome results
None listed