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

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

Time frame: Baseline; study week 8 / study end

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

Time frame: 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

Time frame: Baseline; study week 1-8 / study end

Changes in maximum flow rate [mL/s] as assessed by urodynamics and their relation to clinical outcomes

Time frame: Baseline; study week 8 / study end

Changes in vesicoureterorenal reflux (VUR) as assessed by videography during urodynamics and their relation to clinical outcomes

Time frame: Baseline; study week 8 / study end

Changes in pelvic floor activity as assessed by electromyography (EMG) during urodynamics and their relation to clinical outcomes

Time frame: Baseline; study week 8 / study end

Changes in bladder storage and voiding parameters and their relation to clinical outcomes

Assessed by a bladder diary

Time frame: 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

Time frame: 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."

Time frame: 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."

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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

Time frame: 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

Time frame: 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 \[mmHg\]

Time frame: Baseline; study week 8 / study end

Changes in rectal compliance [mL/cmH2O] during anorectal manometry and barostat assessment and their relation to clinical outcomes

Time frame: 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.

Time frame: 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: * infection - Urinary Tract Infection (UTI) * infection - other than UTI * skin irritation at the electrode site * pressure ulcer * severe neurological deterioration * severe or sudden increase in pain * severe or sudden increase in spasticity * deep vein thrombosis / pulmonary embolism * autonomic dysreflexia * urgent (unexpected) transfer/admittance to an acute care facility

Time frame: During complete study period