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Many patients with neurological diseases suffer from neurogenic lower urinary tract dysfunction (NLUTD), which often severely impairs quality of life, due to urinary urgency with or without incontinence and voiding dysfunction. In addition, the upper urinary tract may be jeopardized because of high intravesical pressure caused by detrusor overactivity (DO) with concurrent detrusor-sphincter-dyssynergia and/or low bladder compliance.
The treatment of NLUTD is a challenge since conventional conservative therapies often fail and more invasive treatments such as intradetrusor onabotulinumtoxinA injections, bladder augmentation and urinary diversion have to be considered. Neuromodulation therapies including tibial nerve stimulation (TNS) may be alternative non-invasive treatment options.
Indeed, TNS is an effective and safe treatment for idiopathic overactive bladder proven in randomised controlled trials (RCTs), but its value in neurological patients is unclear. In a recent systematic review, the investigators found evidence that TNS might become a promising treatment option for NLUTD, however, more reliable data from well-designed RCTs are urgently needed to reach definitive conclusions.
However, this study will be the first adequately sampled and powered, randomised, sham-controlled, double-blind trial assessing transcutaneous TNS (TTNS) for NLUTD. It will provide significant insights into the efficacy of TTNS in patients suffering from NLUTD and in the case that this treatment is really effective in the neurological population, the investigators findings would completely revolutionize the management of NLUTD in daily clinical practice. Moreover, this interdisciplinary clinical trial will relevantly influence the neurological and urological approach in the management of NLUTD promoting future collaborative projects improving patients' medical care and underlying the pioneering role of Switzerland in the rapidly developing and ambitious research field of neuro-urology.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Transcutaneous tibial nerve stimulation (TTNS) | Experimental |
| |
| TTNS sham stimulation | Sham Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Experimental TTNS | Device | 30-minute TTNS intervention is performed 2 days a week during a treatment period of 6 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Success of TTNS | Success of TTNS defined as:
| study week 8 / study end |
| Measure | Description | Time Frame |
|---|---|---|
| Volumetric changes during urodynamics and their relation to clinical outcomes | Cystometric capacity [mL], volume at first DO [mL], voided volume [mL] and post void residual [mL] as assessed by urodynamic measurement | Baseline; study week 8 / study end |
| Changes in bladder compliance [mL/cmH2O] during urodynamics and their relation to clinical outcomes |
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Inclusion Criteria:
Informed consent
Age ≥18 years
Last urethro-cystoscopy and bladder washing cytology within 1 year before inclusion
Last urodynamic investigation within 6 months and no change of bladder medication since then
Refractory LUTD due to a neurological disorder:
Motor response induced by TTNS stimulation at least at one leg
Willing not to change or start any new medications or treatments for the LUT during the entire study period (from screening till unblinding)
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Antwerp | Edegem | Belgium | ||||
| University of Sao Paulo School of Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37204144 | Derived | Stalder SA, Gross O, Anderson CE, Bachmann LM, Baumann S, Birkhauser V, Bywater M, Del Popolo G, Engeler DS, Agro EF, Friedl S, Grilo N, Kiss S, Koschorke M, Leitner L, Liechti MD, Mehnert U, Musco S, Sadri H, Stachele L, Tornic J, van der Lely S, Wyler S, Kessler TM. bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction. BJU Int. 2023 Sep;132(3):343-352. doi: 10.1111/bju.16081. Epub 2023 Jun 13. |
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| Sham TTNS | Device | 30-minute sham intervention is performed 2 days a week during a treatment period of 6 weeks |
|
| Baseline; study week 8 / study end |
| Pressure changes during urodynamics and their relation to clinical outcomes | Maximum DO pressure [cmH2O], detrusor leak-point pressure [cmH2O], maximum detrusor pressure [cmH2O] during storage phase, maximum detrusor pressure [cmH2O] during voiding phase, detrusor pressure at maximum flow rate [cmH2O] as assessed by urodynamic measurement | Baseline; study week 1-8 / study end |
| Changes in maximum flow rate [mL/s] as assessed by urodynamics and their relation to clinical outcomes | Baseline; study week 8 / study end |
| Changes in vesicoureterorenal reflux (VUR) as assessed by videography during urodynamics and their relation to clinical outcomes | Baseline; study week 8 / study end |
| Changes in pelvic floor activity as assessed by electromyography (EMG) during urodynamics and their relation to clinical outcomes | Baseline; study week 8 / study end |
| Changes in bladder storage and voiding parameters and their relation to clinical outcomes | Assessed by a bladder diary | Baseline; once per week during the TTNS intervention period; study week 8 / study end |
| Changes in bowel diary parameters and their relation to clinical outcomes | Assessed by a bowel diary | Baseline; study week 8 / study end |
| Goal attainment scaling assessed by a self-assessment goal achievement (SAGA) questionnaire | The baseline SAGA module asks patients to rate the importance of 9 prespecified (fixed) treatment goals that describe reducing the following LUTS: frequency (daytime and nighttime); sensation of pressure; primary sensation to use the bathroom; bladder voiding; starting or maintaining a urine stream; urine loss when coughing, laughing, exercising, or sneezing; urine leakage; and urgency. In addition to the 9 fixed goals, patients can list up to 5 additional (open) treatment goals. Patients rate the importance of each goal using a 5-point scale ranging from "not very important goal" to "very important goal." In the SAGA follow-up module, patients rate their achievement of each individualized goal and overall goal achievement with a 5-point scale ranging from "did not achieve goal" to "greatly exceeded goal." | Baseline; study week 8 / study end |
| Changes in International Prostate Symptom (IPSS) questionnaire and their relation to clinical outcomes | The IPSS ("International Prostate Symptom Questionnaire") score is based on questions concerning urinary symptoms and quality of life (QoL). It consists of 8 items covering 7 urinary symptoms related dimensions (subscales) and 1 additional item assessing quality of life. Each item is rated on a 6-point scale (0=not at all; 5=almost always). The lowest possible score in the total IPSS score is 0 (asymptomatic); the highest possible score is 35 (symptomatic). The QoL index is rated on a 7-point scale, with 0 indicating "delighted" and 6 "terrible." | Baseline; once per week during the TTNS intervention period; study week 8 / study end |
| Changes in urinary symptoms as assessed by the Urinary Symptom Profile (USP) questionnaire and their relation to clinical outcomes | The USP ("Urinary Symptom Profile") score is based on questions concerning urinary symptoms and their severity in males and females. It consists of 13 items covering 3 dimensions (subscales) with 7 overactive bladder (OAB), 3 stress urinary incontinence (SUI), and 3 low stream (LS) related items. Each item is rated on a 4-point scale. The lowest score is 0 (asymptomatic); the highest score is 3 (symptomatic). | Baseline; once per week during the TTNS intervention period; study week 8 / study end |
| Changes in Qualiveen questionnaire scores and their relation to clinical outcomes | Qualiveen-30 assesses the Specific Impact of Urinary Problems (SIUP) on Quality of Life. It consists of 30 items covering 4 domains, namely inconvenience (9 questions), restrictions (8 questions), fears (8 questions), and impact on daily life (5 questions). Each item is rated on a 5-point ordinal scale (0=asymptomatic; 4=symptomatic). The index of the SIUP on Quality of Life is the mean of the four individual scores. The lowest possible overall score in the Qualiveen-30 is 0 (Urinary problems have no specific impact on QoL); the highest possible score is 30 (Urinary problems have a huge specific impact on QoL). | Baseline; once per week during the TTNS intervention period; study week 8 / study end |
| Changes in Female Sexual Function Index (FSFI) and their relation to clinical outcomes | The FSFI ("Female Sexual Function Index") is based on questions concerning female sexual functions. It consists of 19 items covering 6 domains, namely sexual desire, arousal (both subjective and physiologic), lubrication, orgasm, satisfaction, and pain. The lowest possible score in the total FSFI is 2 (asymptomatic); the highest possible score is 36 (symptomatic). | Baseline; once per week during the TTNS intervention period; study week 8 / study end |
| Changes in International Index of Erectile Function (IIEF) and their relation to clinical outcomes | The IIEF ("International Index of Erectile Function") is based on questions concerning erectile dysfunction. It consists of 15 items covering 5 domains, namely erectile functioning, orgasmic functioning, sexual desire, and intercourse satisfaction along with a fifth component which encompasses the concept of overall sexual satisfaction. While items 1-10 are rated on a 6-point Likert-type scale from 0 to 5, items 11-15 are rated on a 5-point Likert-type scale from 1 to 5. Higher scores are reflecting less dysfunction. Domain scores are computed by summing the sores for individual items in each domain. | Baseline; once per week during the TTNS intervention period; study week 8 / study end |
| Variability and validity of University of South Australia Urinary Symptom Assessment questionnaire (USA2) for treatment follow-up | The USA2 ("University of South Australia Urinary Symptom Assessment") assesses multiple dimensions of urgency sensation. 10 items are rated on a 6-point Likert-type scale from 0 to 5. Lower scores are reflecting lesser urgency symptoms. Domain scores are computed by summing the sores for individual items in each domain. | Baseline; once per week during the TTNS intervention period; study week 8 / study end |
| Changes in Neurogenic Bowel Dysfunction (NBD) questionnaire and their relation to clinical outcomes | The NBD ("Neurogenic Bowel Dysfunction") score is based on questions concerning constipation and fecal incontinence and was developed for and validated in the spinal cord injury population. It consists of 10 items. The lowest possible score in the total NBD is 0 (asymptomatic); the highest possible score is 47 (symptomatic). The interpretation of the total NBD score is very minor NBD (0-6), minor NBD (7-9), moderate NBD (10-13), and severe NBD (≥14). | Baseline; once per week during the TTNS intervention period; study week 8 / study end |
| Changes in neurophysiology measurements of evoked potentials (EPs) as well as nerve conduction measurements and their relation to clinical outcomes | Baseline; once per week during the TTNS intervention period; study week 8 / study end |
| Volumetric changes during rectal sensitivity testing and barostat assessment and their relation to clinical outcomes | Initial sensation [mL], volume at urge to defecate [mL], maximum tolerated volume [mL] as assessed by rectal sensitivity testing; rectal capacity [mL] assessed by barostat assessment | Baseline; study week 8 / study end |
| Pressure changes during anorectal manometry and barostat assessment and their relation to clinical outcomes | Basal Internal anal sphincter pressure [mmHg], squeeze external anal sphincter pressure [mmHg], relaxation internal anal sphincter pressure during defecation [mmHg], intraabdominal pressure during defecation [mmHg] | Baseline; study week 8 / study end |
| Changes in rectal compliance [mL/cmH2O] during anorectal manometry and barostat assessment and their relation to clinical outcomes | Baseline; study week 8 / study end |
| Changes in defecatory disorder [Rao's classification] identified during anorectal manometry and their relation to clinical outcomes | Anorectal manometry is the preferable test for defecatory disorder. Rao's classification describes the four types manometric patterns (I-IV) that are identified through manometric assessments. | Baseline; study week 8 / study end |
| Incidence of side effects as well as number and intensity/severity (mild/moderate/severe) of AEs and SAE | Categories:
| During complete study period |
| São Paulo |
| Brazil |
| Careggi University Hospital | Florence | Italy |
| Tor Vergata University Hospital | Rome | Italy |
| Inselspital Bern, University Hospital | Bern | Canton of Bern | Switzerland |
| Cantonal Hospital Winterthur | Winterthur | Canton of Zurich | Switzerland |
| Cantonal Hospital Aarau | Aarau | Switzerland |
| REHAB Basel | Basel | Switzerland |
| EOC - Regional Hospital Bellinzona and Valleys | Bellinzona | Switzerland |
| Centre hospitalier universitaire vaudois CHUV | Lausanne | 1011 | Switzerland |
| Cantonal Hospital St. Gallen | Sankt Gallen | Switzerland |
| Balgrist University Hospital | Zurich | Switzerland |