About this trial
Most patients with spinal cord injury (SCI) develop neurogenic lower urinary tract dysfunction (NLUTD), one of the most devastating sequelae of SCI which ultimately can lead to renal failure. We urgently need an intervention that prevents NLUTD before irreversible damage occurs. Neuromodulation procedures are a promising avenue so that we investigate the effect of transcutaneous tibial nerve stimulation (TTNS) in patients with acute SCI.
This nationwide randomized, sham-controlled, double-blind multicentre clinical trial includes all SCI centres in Switzerland (Basel, Nottwil, Sion, Zürich). Patients are randomly assigned to VERUM TTNS (active stimulation, n=57) and SHAM stimulation (n=57) groups in a 1:1 allocation using computer-generated permuted block randomisation lists stratified on study centre and lower extremity motor score. Daily 30-minute sessions are performed five times a week during an intervention period of 6-9 weeks. The primary outcome of this study is the success of TTNS to prevent neurogenic DO jeopardizing the upper urinary tract, assessed by urodynamics at 1 year after SCI or any earlier time point if DO treatment is necessary (study end). Secondary outcome measures are bladder diary parameters, clinical symptom scores assessed by standardized and validated questionnaires. Furthermore, neurophysiological and neuroimaging outcome measures are assessed as well as, biochemical and molecular changes. Tertiary outcome measure is the safety of TTNS.
Before the actual start of the TASCI RCT, start-up activities will include a piloting phase on groups of healthy volunteers and patients. The goal during this phase is to evaluate the feasibility of the experimental setup, in particular for the TTNS and SHAM intervention, but also to test the setup of the different pre and post assessments (e.g. neurophysiology and neuroimaging tests). Groups of up to 15 participants each will be enrolled in a few consecutive pilot studies allowing for fine tuning and small adaptations in between, if appropriate.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age >18 years
Patients with acute SCI (traumatic SCI and sudden onset (<7 days) non-traumatic SCI) within 40 days after injury
Patients with acute SCI at cervical or thoracic level
Willing to take part and follow the requirements of the TASCI protocol (up to one year after SCI)
Disqualifiers
Contraindications to the investigational product
DO with contractions greater than 40 cmH2O at a bladder filling volume of less than 500mL at baseline visit
Treatment with antimuscarinics or with mirabegron
Known or suspected non-adherence, drug or alcohol abuse
Trial design
Parallel
Treatments tested in this trial
VERUM TTNS
Device* Daily 30-minute TTNS intervention is performed 5 days a week during a treatment period of 6-9 weeks, until 3-month post assessments * During a preparation phase of several minutes, sensory and motor thresholds are assessed and stimulation intensities are adjusted for the following 30-minute treatment phase
SHAM TTNS
Device* Daily 30-minute SHAM intervention is performed 5 days a week during a treatment period of 6-9 weeks, until 3-month post assessments * During a preparation phase of several minutes, sensory and motor thresholds are assessed and stimulation intensities are adjusted for the following 30-minute treatment phase
Treatment groups
Trial outcomes
Primary outcomes
The occurrence of neurogenic DO jeopardizing the upper urinary tract
Defined as composite measure: Urodynamic assessment establishing DO amplitude ≥40 cmH2O; or else initiation of DO treatment (with antimuscarinics and/or intradetrusor onabotulinumtoxinA injections)
Secondary outcomes
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
Changes in bladder compliance [mL/cmH2O] during urodynamics and their relation to clinical outcomes
Pressure changes during urodynamics and their relation to clinical outcomes
Maximum DO amplitude \[cmH2O\], 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
Changes in maximum flow rate [mL/s] as assessed by urodynamics and their relation to clinical outcomes
Other outcomes
Incidence of side effects as well as number and intensity/severity (mild/moderate/severe) of adverse events (AEs) and serious adverse events (SAEs) for the following categories:
* infection - Urinary Tract Infection (UTI) * infection - other than UTI * skin irritation at the electrode site * irritation-related symptoms (e.g. dysuria, hematuria) immediately following a LUT intervention * neuro-urological deterioration * pressure ulcer * neurological deterioration * increase in pain * increase in spasticity * deep vein thrombosis / pulmonary embolism * autonomic dysreflexia * transfer/admittance to an acute care facility
Sponsors and contacts
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University of Zurich
Lead sponsor
Swiss National Science Foundation
Collaborator
Clinique Romande de Readaptation
Collaborator
Rehab Basel
Collaborator
Swiss Paraplegic Research, Nottwil
Collaborator
BioMedical Research Forschungslabor für Urologie, University of Bern
Collaborator
Universidade do Porto
Collaborator
Center for Lower Urinary Tract Research School of Medicine, University of Pittsburgh
Collaborator