Bladder and TranscUtaneous Tibial Nerve Stimulation for nEurogenic Lower Urinary Tract Dysfunction

NCT04315142 | Terminated

• 1 other identifier: bTUNED
• Study Type: interventional
• Target: 48
• Locations: 4 countries
• Sites: 12

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.

Conditions

Neurogenic Bladder Dysfunction

Keywords

Randomized; Sham-controlled; Transcutaneous tibial nerve stimulation (TTNS); Neurogenic detrusor overactivity; Neuromodulation

Outcome Measures

Primary Outcomes (1)

• Success of TTNS

  Success of TTNS defined as: * ≥50% reduction in incontinence rates per 24 hours and/or ≥50% reduction in micturition/catheterization frequency per 24 hours in patients with neurogenic overactive bladder (OAB) * Reduction of post void residual (PVR) below 25% of bladder capacity if bladder capacity * 100 mL, or below 50% of bladder capacity if bladder capacity \<100 mL in patients with neurogenic voiding dysfunction * In patients with combined neurogenic OAB and neurogenic voiding dysfunction: The success criteria of leading symptom/dysfunction will be chosen

  study week 8 / study end

Secondary Outcomes (22)

• Volumetric changes during urodynamics and their relation to clinical outcomes

  Baseline; study week 8 / study end

• Changes in bladder compliance [mL/cmH2O] during urodynamics and their relation to clinical outcomes

  Baseline; study week 8 / study end

• Pressure changes during urodynamics and their relation to clinical outcomes

  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

Study Arms (2)

Transcutaneous tibial nerve stimulation (TTNS)

EXPERIMENTAL

Device: Experimental TTNS

TTNS sham stimulation

SHAM COMPARATOR

Device: Sham TTNS

Interventions

Experimental TTNS DEVICE

30-minute TTNS intervention is performed 2 days a week during a treatment period of 6 weeks

Transcutaneous tibial nerve stimulation (TTNS)

Sham TTNS DEVICE

30-minute sham intervention is performed 2 days a week during a treatment period of 6 weeks

TTNS sham stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent
• Age ≥18 years
• Last urodynamic investigation within 6 months and no change of bladder medication since then
• Refractory LUTD due to a neurological disorder:
• 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)
• 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)
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (12)

University Hospital Antwerp

Edegem, Belgium

Location

University of Sao Paulo School of Medicine

São Paulo, Brazil

Location

Careggi University Hospital

Florence, Italy

Location

Tor Vergata University Hospital

Rome, Italy

Location

Inselspital Bern, University Hospital

Bern, Canton of Bern, Switzerland

Location

Cantonal Hospital Winterthur

Winterthur, Canton of Zurich, Switzerland

Location

Cantonal Hospital Aarau

Aarau, Switzerland

Location

REHAB Basel

Basel, Switzerland

Location

EOC - Regional Hospital Bellinzona and Valleys

Bellinzona, Switzerland

Location

Centre hospitalier universitaire vaudois CHUV

Lausanne, 1011, Switzerland

Location

Cantonal Hospital St. Gallen

Sankt Gallen, Switzerland

Location

Balgrist University Hospital

Zurich, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 37204144 DERIVED

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 19, 2020
• Study Start: March 1, 2020
• Primary Completion: July 30, 2025
• Study Completion: July 30, 2025
• Last Updated: August 11, 2025

Record last verified: 2024-11

Locations

BR (1); IT (2); BE (1); CH (8)