Clinical trial NCT04315142: Bladder and TranscUtaneous Tibial Nerve Stimulation for NEurogenic Lower Urinary Tract Dysfunction
Official title: Transcutaneous Tibial Nerve Stimulation (TTNS) for Treating Neurogenic Lower Urinary Tract Dysfunction: a Multicentre, Randomised, Sham-controlled, Double-blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neurogenic Bladder Dysfunction
Keywords: Randomized
Sham-controlled
Transcutaneous tibial nerve stimulation (TTNS)
Neurogenic detrusor overactivity
Neuromodulation
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2020-03-19
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

  1. Neurogenic OAB (i.e. urgency frequency syndrome with or without urgency incontinence) refractory to antimuscarinics (pharmacotherapy for at least 4 weeks with at least 2 antimuscarinics)
  2. Neurogenic voiding dysfunction (i.e. incomplete bladder emptying/incomplete / complete urinary retention) refractory to alpha-blocker (pharmacotherapy with an alpha-blocker for at least 4 weeks)
  3. Combination of neurogenic OAB and neurogenic voiding dysfunction (i.e. urgency frequency syndrome with or without urgency incontinence and incomplete / complete urinary retention) refractory to antimuscarinics (pharmacotherapy for at least 4 weeks with at least 2 antimuscarinics) and alpha-blocker (pharmacotherapy with an alpha- blocker for at least 4 weeks)
* 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:

* Contraindications to the investigational product
* Known or suspected non-adherence, drug or alcohol abuse
* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia
* Participation in another study with investigational drug or product within the 30 days preceding and during the present study
* Neuromodulation treatment for urological indication in the last six months or ongoing
* Botulinum toxin injections in the detrusor and/or urethral sphincter in the last six months
* Women who are pregnant or breast feeding
* Intention to become pregnant during the course of the study
* Individuals especially in need of protection (according to Research with Human Subjects published by the Swiss Academy of Medical Sciences \[www.samw.ch/en/News/News.html\]
* Enrolment of the investigator, his/her family members, employees and other dependent persons

Primary outcomes:
measure: Success of TTNS
timeFrame: study week 8 / study end
Secondary outcomes:
measure: Volumetric changes during urodynamics and their relation to clinical outcomes
timeFrame: Baseline; study week 8 / study end
measure: Changes in bladder compliance [mL/cmH2O] during urodynamics and their relation to clinical outcomes
timeFrame: Baseline; study week 8 / study end
measure: Pressure changes during urodynamics and their relation to clinical outcomes
timeFrame: Baseline; study week 1-8 / study end
measure: Changes in maximum flow rate [mL/s] as assessed by urodynamics and their relation to clinical outcomes
timeFrame: Baseline; study week 8 / study end
measure: Changes in vesicoureterorenal reflux (VUR) as assessed by videography during urodynamics and their relation to clinical outcomes
timeFrame: Baseline; study week 8 / study end
measure: Changes in pelvic floor activity as assessed by electromyography (EMG) during urodynamics and their relation to clinical outcomes
timeFrame: Baseline; study week 8 / study end
measure: Changes in bladder storage and voiding parameters and their relation to clinical outcomes
timeFrame: Baseline; once per week during the TTNS intervention period; study week 8 / study end
measure: Changes in bowel diary parameters and their relation to clinical outcomes
timeFrame: Baseline; study week 8 / study end
measure: Goal attainment scaling assessed by a self-assessment goal achievement (SAGA) questionnaire
timeFrame: Baseline; study week 8 / study end
measure: Changes in International Prostate Symptom (IPSS) questionnaire and their relation to clinical outcomes
timeFrame: Baseline; once per week during the TTNS intervention period; study week 8 / study end
measure: Changes in urinary symptoms as assessed by the Urinary Symptom Profile (USP) questionnaire and their relation to clinical outcomes
timeFrame: Baseline; once per week during the TTNS intervention period; study week 8 / study end
measure: Changes in Qualiveen questionnaire scores and their relation to clinical outcomes
timeFrame: Baseline; once per week during the TTNS intervention period; study week 8 / study end
measure: Changes in Female Sexual Function Index (FSFI) and their relation to clinical outcomes
timeFrame: Baseline; once per week during the TTNS intervention period; study week 8 / study end
measure: Changes in International Index of Erectile Function (IIEF) and their relation to clinical outcomes
timeFrame: Baseline; once per week during the TTNS intervention period; study week 8 / study end
measure: Variability and validity of University of South Australia Urinary Symptom Assessment questionnaire (USA2) for treatment follow-up
timeFrame: Baseline; once per week during the TTNS intervention period; study week 8 / study end
measure: Changes in Neurogenic Bowel Dysfunction (NBD) questionnaire and their relation to clinical outcomes
timeFrame: Baseline; once per week during the TTNS intervention period; study week 8 / study end
measure: Changes in neurophysiology measurements of evoked potentials (EPs) as well as nerve conduction measurements and their relation to clinical outcomes
timeFrame: Baseline; once per week during the TTNS intervention period; study week 8 / study end
measure: Volumetric changes during rectal sensitivity testing and barostat assessment and their relation to clinical outcomes
timeFrame: Baseline; study week 8 / study end
measure: Pressure changes during anorectal manometry and barostat assessment and their relation to clinical outcomes
timeFrame: Baseline; study week 8 / study end
measure: Changes in rectal compliance [mL/cmH2O] during anorectal manometry and barostat assessment and their relation to clinical outcomes
timeFrame: Baseline; study week 8 / study end
measure: Changes in defecatory disorder [Rao's classification] identified during anorectal manometry and their relation to clinical outcomes
timeFrame: Baseline; study week 8 / study end
measure: Incidence of side effects as well as number and intensity/severity (mild/moderate/severe) of AEs and SAE
timeFrame: During complete study period
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: University Hospital Antwerp
city: São Paulo
country: Brazil
facility: University of Sao Paulo School of Medicine
city: Florence
country: Italy
facility: Careggi University Hospital
city: Rome
country: Italy
facility: Tor Vergata University Hospital
city: Winterthur
country: Switzerland
facility: Cantonal Hospital Winterthur
state: Zurich
city: Aarau
country: Switzerland
facility: Cantonal Hospital Aarau
city: Basel
country: Switzerland
facility: REHAB Basel
city: Bellinzona
country: Switzerland
facility: EOC - Regional Hospital Bellinzona and Valleys
city: Berne
country: Switzerland
facility: Inselspital Bern, University Hospital
city: Lausanne
country: Switzerland
facility: Centre hospitalier universitaire vaudois CHUV
city: Sankt Gallen
country: Switzerland
facility: Cantonal Hospital St. Gallen
city: Zürich
country: Switzerland
facility: Balgrist University Hospital
Study officials:
References: