Transcutaneous Tibial Nerve Stimulation in Acute Spinal Cord Injury

NCT03965299 | Recruiting DMC

• 1 other identifier: 2019-00074
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Spinal Cord Injury, Acute

Keywords

randomized, sham-controlled, double-blind trial; transcutaneous tibial nerve stimulation; spinal cord injury; neurogenic detrusor overactivity; neuromodulation; electrical stimulation; paraplegia; tetraplegia; urodynamics

Outcome Measures

Primary Outcomes (1)

• 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)

  up to 12 months after SCI

Secondary Outcomes (41)

• Volumetric changes during urodynamics and their relation to clinical outcomes

  Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end

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

  Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end

• Pressure changes during urodynamics and their relation to clinical outcomes

  Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end

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

  Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end

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

  Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end

Other Outcomes (1)

• 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:

  During complete study period, up to 12 months

Study Arms (2)

VERUM transcutaneous tibial nerve stimulation (TTNS)

EXPERIMENTAL

Device: VERUM TTNS

SHAM transcutaneous tibial nerve stimulation (TTNS)

SHAM COMPARATOR

Device: SHAM TTNS

Interventions

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

VERUM transcutaneous tibial nerve stimulation (TTNS)

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

SHAM transcutaneous tibial nerve stimulation (TTNS)

Eligibility Criteria

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

You may qualify if:

• 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)
• no percutaneous tibial nerve stimulation (PTNS)
• no functional electrical stimulation (FES), apart from upper limb FES
• no electrical muscle stimulation (EMS)
• Informed Consent

You may not qualify if:

• 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
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
• Participation in another study with investigational drug or product within the 30 days preceding and during the present study
• Neuromodulation treatment for urological or bowel indication in the last six months or ongoing
• Botulinum toxin injections in the detrusor and/or urethral sphincter in the last six months
• Bilaterally absent tibial nerve compound muscle action potential (cMAP, amplitude \< 1mV)
• 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
• Pre-existing or concomitant medical condition apart from SCI that might pose a safety issue or would interfere with interpretation of study results or study conduct (e.g. Parkinson's disease, neurodegenerative disorders including multiple sclerosis and amyotrophic lateral sclerosis, urological malignancies)

Sponsors & Collaborators

• University of Zurich: lead
• 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
• Translational Neuro-Urology Department of Biomedicine, University of Porto: collaborator
• Center for Lower Urinary Tract Research School of Medicine, University of Pittsburgh: collaborator

Study Sites (4)

Department of Neuro-Urology, Spinal Cord Injury Centre & Research, Balgrist University Hospital

Zurich, Canton of Zurich, 8008, Switzerland

RECRUITING

REHAB Basel

Basel, Switzerland

RECRUITING

Swiss Paraplegic Centre

Nottwil, Switzerland

RECRUITING

Spinal Cord Injury Department, Clinique romande de réadaption

Sion, Switzerland

RECRUITING

Related Publications (8)

• Birkhauser V, Liechti MD, Anderson CE, Bachmann LM, Baumann S, Baumberger M, Birder LA, Botter SM, Bueler S, Cruz CD, David G, Freund P, Friedl S, Gross O, Hund-Georgiadis M, Husmann K, Jordan X, Koschorke M, Leitner L, Luca E, Mehnert U, Mohr S, Mohammadzada F, Monastyrskaya K, Pfender N, Pohl D, Sadri H, Sartori AM, Schubert M, Sprengel K, Stalder SA, Stoyanov J, Stress C, Tatu A, Tawadros C, van der Lely S, Wollner J, Zubler V, Curt A, Pannek J, Brinkhof MWG, Kessler TM. TASCI-transcutaneous tibial nerve stimulation in patients with acute spinal cord injury to prevent neurogenic detrusor overactivity: protocol for a nationwide, randomised, sham-controlled, double-blind clinical trial. BMJ Open. 2020 Aug 13;10(8):e039164. doi: 10.1136/bmjopen-2020-039164.

  PMID: 32792454 BACKGROUND

• Liechti MD, van der Lely S, Stalder SA, Anderson CE, Birkhauser V, Bachmann LM, Brinkhof MWG, Curt A, Jordan X, Leitner L, Mehnert U, Mohr S, Pannek J, Schubert M, Kessler TM; TASCI Study Group. Update from TASCI, a Nationwide, Randomized, Sham-controlled, Double-blind Clinical Trial on Transcutaneous Tibial Nerve Stimulation in Patients with Acute Spinal Cord Injury to Prevent Neurogenic Detrusor Overactivity. Eur Urol Focus. 2020 Sep 15;6(5):877-879. doi: 10.1016/j.euf.2019.09.019. Epub 2019 Oct 8.

  PMID: 31601539 BACKGROUND

• Anderson CE, Birkhauser V, Stalder SA, Bachmann LM, Curt A, Jordan X, Leitner L, Liechti MD, Mehnert U, Mohr S, Pannek J, Schubert M, van der Lely S, Kessler TM, Brinkhof MWG. Optimizing clinical trial design using prospective cohort study data: a case study in neuro-urology. Spinal Cord. 2021 Sep;59(9):1003-1012. doi: 10.1038/s41393-020-00588-z. Epub 2020 Nov 24.

  PMID: 33235299 BACKGROUND

• Bueler S, Yiannakas MC, Damjanovski Z, Freund P, Liechti MD, David G. Optimized multi-echo gradient-echo magnetic resonance imaging for gray and white matter segmentation in the lumbosacral cord at 3 T. Sci Rep. 2022 Oct 3;12(1):16498. doi: 10.1038/s41598-022-20395-1.

  PMID: 36192560 BACKGROUND

• Bueler S, Freund P, Kessler TM, Liechti MD, David G. Improved inter-subject alignment of the lumbosacral cord for group-level in vivo gray and white matter assessments: A scan-rescan MRI study at 3T. PLoS One. 2024 Apr 16;19(4):e0301449. doi: 10.1371/journal.pone.0301449. eCollection 2024.

  PMID: 38626171 BACKGROUND

• Stalder SA, van der Lely S, Anderson CE, Birkhauser V, Curt A, Gross O, Leitner L, Mehnert U, Schubert M, Tornic J, Kessler TM, Liechti MD. Development of a Sham Protocol to Investigate Transcutaneous Tibial Nerve Stimulation in Randomised, Sham-Controlled, Double-Blind Clinical Trials. Biomedicines. 2023 Jul 7;11(7):1931. doi: 10.3390/biomedicines11071931.

  PMID: 37509569 BACKGROUND

• Beghini L, Bueler S, Liechti MD, Jaffray A, David G, Vannesjo SJ. Optimized navigator-based correction of breathing-induced B0 field fluctuations in multi-echo gradient-echo imaging of the spinal cord. Magn Reson Med. 2025 Jul;94(1):215-230. doi: 10.1002/mrm.30475. Epub 2025 Mar 4.

  PMID: 40034000 BACKGROUND

• Bueler S, Anderson CE, Birkhauser V, Freund P, Gross O, Kessler TM, Kundig CW, Leitner L, Mahnoor N, Mehnert U, Rothlisberger R, Stalder SA, van der Lely S, Zipser CM, David G, Liechti MD. Remote neurodegeneration in the lumbosacral cord one month after spinal cord injury: a cross-sectional MRI study. Ann Clin Transl Neurol. 2025 Mar;12(3):523-537. doi: 10.1002/acn3.52298. Epub 2025 Jan 27.

  PMID: 39869509 BACKGROUND

Related Links

• TASCI on Swiss National Science Foundation grant database

MeSH Terms

Conditions

Spinal Cord Injuries; Paraplegia; Quadriplegia

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Thomas M. Kessler, Prof. Dr. med.

  University of Zurich

  STUDY CHAIR

• Thomas M. Kessler, Prof. Dr. med.

  Balgrist University Hospital

  PRINCIPAL INVESTIGATOR

• Armin Curt, Prof. Dr. med.

  Balgrist University Hospital

  PRINCIPAL INVESTIGATOR

• Martin Brinkhof, Dr.

  Swiss Paraplegic Research, Nottwil

  PRINCIPAL INVESTIGATOR

• Jürgen Pannek, Prof. Dr. med.

  Swiss Paraplegic Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas M. Kessler, Prof. Dr. med.

CONTACT

+41 44 386 39 07; thomas.kessler@balgrist.ch

Martina D. Liechti, Dr. sc. ETH

CONTACT

+41 44 386 39 07; martina.liechti@balgrist.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The only unmasked person involved in the trial is the operator who will be responsible for the daily application of the study intervention at the patient. The role of an operator can be occupied by a research assistant/study nurse or investigator not involved in the clinical management and assessment of clinical outcomes. Thus, patients and care providers involved with clinical assessments are blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2019
• First Posted: May 29, 2019
• Study Start: June 19, 2019
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: Post-publication data packages, containing the analysis data set presented in scientific reports will be available starting 6 months after the publication date. Data that are not being prepared for publication will be available to secondary users starting 4 years after study completion or discontinuation. All data will be kept for at least 10 years after study completion or discontinuation.
• Access Criteria: Requests for data access will be reviewed by the TASCI steering committee, which includes the four project PIs and representatives from each of the participating study centers. The steering committee will request a project plan, including at a minimum an abstract and a list of author names and roles, from the leaders of all projects wishing to use TASCI study data. Project plans will be evaluated on the basis of scientific validity, and also on whether they include adequate measures to protect patient privacy. Secondary users will be asked to sign a data use agreement.

Locations

CH (4)