Transcutaneous Tibial Nerve Stimulation (TTNS) for Treating Neurogenic Lower Urinary Tract Dysfunction: A Multicentre, Randomised, Sham-controlled, Double-blind Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 48
- 试验地点
- 13
- 主要终点
- Success of TTNS
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •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)
排除标准
- •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
结局指标
主要结局
Success of TTNS
时间窗: study week 8 / study end
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
次要结局
- 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)
- 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 maximum flow rate [mL/s] as assessed by 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(Baseline; once per week during the TTNS intervention period; 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)
- Pressure changes during urodynamics and their relation to clinical outcomes(Baseline; study week 1-8 / 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 International Index of Erectile Function (IIEF) and their relation to clinical outcomes(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)
- Changes in bowel diary parameters and their relation to clinical outcomes(Baseline; study week 8 / study end)
- Changes in urinary symptoms as assessed by the Urinary Symptom Profile (USP) questionnaire and their relation to clinical outcomes(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(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(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(Baseline; study week 8 / study end)
- Changes in defecatory disorder [Rao's classification] identified during anorectal manometry and their relation to clinical outcomes(Baseline; study week 8 / study end)
- Incidence of side effects as well as number and intensity/severity (mild/moderate/severe) of AEs and SAE(During complete study period)
- Goal attainment scaling assessed by a self-assessment goal achievement (SAGA) questionnaire(Baseline; study week 8 / study end)
- Changes in International Prostate Symptom (IPSS) questionnaire and their relation to clinical outcomes(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(Baseline; once per week during the TTNS intervention period; study week 8 / study end)
- Pressure changes during anorectal manometry and barostat assessment and their relation to clinical outcomes(Baseline; study week 8 / study end)
- Changes in Female Sexual Function Index (FSFI) and their relation to clinical outcomes(Baseline; once per week during the TTNS intervention period; study week 8 / study end)