Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Transcutaneous Tibial Nerve Stimulation in Acute Spinal Cord Injury (TASCI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03965299
Recruitment Status : Recruiting
First Posted : May 29, 2019
Last Update Posted : June 24, 2019
Sponsor:
Collaborators:
Swiss National Science Foundation
Clinique Romande de Readaptation
Rehab Basel
Swiss Paraplegic Centre Nottwil
Swiss Paraplegic Research
BioMedical Research Forschungslabor für Urologie, University of Bern
Translational Neuro-Urology Department of Biomedicine, University of Porto
Center for Lower Urinary Tract Reserach School of Medicine, University of Pittsburgh
Information provided by (Responsible Party):
University of Zurich

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.


Condition or disease Intervention/treatment Phase
Spinal Cord Injury, Acute Device: VERUM TTNS Device: SHAM TTNS Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Prevention
Official Title: Transcutaneous Tibial Nerve Stimulation in Patients With Acute Spinal Cord Injury to Prevent Neurogenic Detrusor Overactivity: A Nationwide Randomised, Sham-controlled, Double-blind Clinical Trial
Estimated Study Start Date : June 21, 2019
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: VERUM transcutaneous tibial nerve stimulation (TTNS) Device: VERUM TTNS
  • Daily 30-minuteTTNS 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 Comparator: SHAM transcutaneous tibial nerve stimulation (TTNS) Device: SHAM TTNS
  • 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




Primary Outcome Measures :
  1. The occurrence of neurogenic DO jeopardizing the upper urinary tract [ Time Frame: up to 12 months after SCI ]
    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 Outcome Measures :
  1. Volumetric changes during urodynamics and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Cystometric capacity [mL], volume at first DO [mL], voided volume [mL] and post void residual [mL] as assessed by urodynamic measurement

  2. Changes in bladder compliance [mL/cmH2O] during urodynamics and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
  3. Pressure changes during urodynamics and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    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

  4. Changes in maximum flow rate [mL/s] as assessed by urodynamics and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
  5. Changes in vesicoureterorenal reflux (VUR) as assessed by videography during urodynamics and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
  6. Changes in pelvic floor activity as assessed by electromyography (EMG) during urodynamics and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
  7. Changes in bladder storage and voiding parameters and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Assessed by a bladder diary

  8. Changes in bowel diary parameters and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Assessed by a bowel diary

  9. Changes in International Prostate Symptom (IPSS) questionnaire and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    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."

  10. Changes in urinary symptoms as assessed by the Urinary Symptom Profile (USP) questionnaire and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    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).

  11. Changes in Qualiveen questionnaire scores and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    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).

  12. Changes in Female Sexual Function Index (FSFI) and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    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).

  13. Changes in International Index of Erectile Function (IIEF) and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    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.

  14. Changes in International Spinal Cord Society (ISCoS) Female / Male sexual function data sets and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
  15. Changes in Neurogenic Bowel Dysfunction (NBD) questionnaire and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    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).

  16. Changes International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) assessment to quantify the severity of the spinal cord injury

  17. Changes in Lower Extremities Motor Scale (LEMS) from International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    LEMS is based on assessments of ISNCSCI and composed from the sum of muscle function grading of the five key muscles of the lower limbs. It consists of a 6-point scale (0=no; 5=normal activity) for each muscle and body site. The lowest possible score in the total LEMS score for one body site is 0 (symptomatic); the highest possible score is 50 (asymptomatic).

  18. Changes in Upper Extremities Motor Scale (UEMS) from International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) protocol [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    UEMS is based on assessments of ISNCSCI and composed from the sum of muscle function grading of the five key muscles of the upper limbs. It consists of a 6-point scale (0=no; 5=normal activity) for each muscle and body site. The lowest possible score in the total LEMS score for one body site is 0 (symptomatic); the highest possible score is 50 (asymptomatic).

  19. Changes in Spinal Cord Independence Measure III (SCIM-III) and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    The SCIM-III ("Spinal Cord Independence Measure III") score is based on questions concerning independence of persons with a spinal cord injured. It consists of 19 items covering 3 domains, self-care, respiration and sphincter management, and mobility. The self-care subscale ranges from 0 to 20. The respiration and sphincter management subscale ranges from 0 to 40. The mobility subscale ranges from 0 to 40. Total score ranges from 0 (symptomatic) to 100 (asymptomatic). Higher scores reflect higher levels of independence.

  20. Changes in neurophysiology measurements of evoked potentials (EPs) as well as nerve conduction measurements and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
  21. Changes in lower urinary tract (LUT) neurophysiology: Current perception thresholds (CPTs) and LUT sensory evoked potentials (LUTSEPs) with their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
  22. Changes in frequency power of surface electromyography (EMG) and electroencephalography (EEG) and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Fast Fourier Transformation analysis for delta, theta, alpha, beta, and gamma band power as assessed via EEG of the cortex and EMG of the muscle

  23. Changes in EMG and EEG coherence measures and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Coherence for EEG and EMG signals computed as cortico-muscular, inter- and intra-muscular coherence for typical EEG/EMG frequency bands (delta, theta, alpha, beta, and gamma).

  24. Changes in white and gray matter area in the lumbosacral enlargement (LSE) and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    White and gray matter areas are obtained by segmenting the T2*-weighted MRI images for white and gray matter at the level of LSE

  25. Changes in white and gray matter area in upper cervical cord (at C2/C3) and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Obtained by segmenting the T2*-weighted MRI images for white and gray matter at the vertebral level C2/C3.

  26. Changes in white and gray matter volume of the conus medullaris (CM) and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    White and gray matter volume are obtained by segmenting the T2*-weighted MRI images for white and gray matter in the CM

  27. Changes in gray and white matter volume in the brain and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Gray and white matter volume in the brain are computed by feeding the whole-brain T1-weighted MRI images into a voxel-based morphometry algorithm. Changes in the gray and white matter volume will be evaluated in urologically relevant brain areas.

  28. Changes in fractional anisotropy (FA) in the brain and spinal cord and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    FA is a common dimensionless measure used in Diffusion Tensor Imaging (DTI) studies and ranges from 0, isotropic movement of water molecules (e.g., cerebrospinal fluid), to 1, fully anisotropic movement of water molecules (e.g., fiber bundles).

  29. Changes in diffusivity in the brain and spinal cord and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Mean, axial, and radial diffusivity (MD, AD, RD) are common measures used in DTI studies providing information about the integrity of the underlying tissue.

  30. Changes in brain and spinal cord tissue microstructure and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Quantitative tissue parameters assessed using MRI Multi-Parameter Mapping.

  31. Expression profile of microRNA (miRNA) in urine and blood as well as their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    MicroRNA (miRNA) sequencing is used to identify regulated miRNAs specific to TTNS intervention in urine and blood.

  32. Changes in inflammatory markers in bladder tissue, blood, and urine, as well as their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
  33. Changes in levels of neurotransmitters (neurotrophins) in blood, and urine, as well as their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Analysis will be performed using ELISA to detect molecules likely to be involved in the underlying molecular mechanisms of neuromodulation.

  34. Changes in the composition of urinary and stool microbiome and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]
    Gut and bladder microbial patterns are determined from stool and urine samples

  35. Changes in bladder tissue and their relation to clinical outcomes [ Time Frame: Baseline; 3 months after SCI; 6 months after SCI; 12 months after SCI / study end ]

Other Outcome Measures:
  1. Incidence of side effects as well as number and intensity/severity (mild/moderate/severe) of AEs and SAE for the following categories: [ Time Frame: During complete study period, up to 12 months ]
    • 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
    • no electrical muscle stimulation (EMS)
  • Informed Consent

Exclusion Criteria:

  • Contraindications to the investigational product
  • 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03965299


Contacts
Layout table for location contacts
Contact: Thomas M. Kessler, Prof. Dr. med. +41 44 386 39 07 thomas.kessler@balgrist.ch
Contact: Martina D. Liechti, Dr. sc. ETH +41 44 386 39 07 martina.liechti@balgrist.ch

Locations
Layout table for location information
Switzerland
REHAB Basel Not yet recruiting
Basel, Switzerland
Contact: Sandra Möhr, pract. med.       s.moehr@rehab.ch   
Principal Investigator: Sandra Möhr, pract. med.         
Swiss Paraplegic Centre Not yet recruiting
Nottwil, Switzerland
Contact: Jürgen Pannek, Prof. Dr. med.       juergen.pannek@paraplegie.ch   
Principal Investigator: Jürgen Pannek, Prof. Dr. med.         
Spinal Cord Injury Department, Clinique romande de réadaption Not yet recruiting
Sion, Switzerland
Contact: Xavier Jordan, Dr. med.       xavier.jordan@crr-suva.ch   
Principal Investigator: Xavier Jordan, Dr. med.         
Department of Neuro-Urology, Spinal Cord Injury Centre & Research, Balgrist University Hospital Recruiting
Zürich, Switzerland, 8008
Contact: Thomas M Kessler, Prof. Dr. med.    +41 44 386 39 07    thomas.kessler@balgrist.ch   
Principal Investigator: Thomas M Kessler, Prof. Dr. med.         
Sponsors and Collaborators
University of Zurich
Swiss National Science Foundation
Clinique Romande de Readaptation
Rehab Basel
Swiss Paraplegic Centre Nottwil
Swiss Paraplegic Research
BioMedical Research Forschungslabor für Urologie, University of Bern
Translational Neuro-Urology Department of Biomedicine, University of Porto
Center for Lower Urinary Tract Reserach School of Medicine, University of Pittsburgh
Investigators
Layout table for investigator information
Study Chair: Thomas M. Kessler, Prof. Dr. med. University of Zurich
Principal Investigator: 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
Principal Investigator: Jürgen Pannek, Prof. Dr. med. Swiss Paraplegic Centre

Additional Information:
Layout table for additonal information
Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT03965299     History of Changes
Other Study ID Numbers: 2019-00074
First Posted: May 29, 2019    Key Record Dates
Last Update Posted: June 24, 2019
Last Verified: May 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Zurich:
randomized, sham-controlled, double-blind trial
transcutaneous tibial nerve stimulation
spinal cord injury
neurogenic detrusor overactivity
neuromodulation
electrical stimulation
paraplegia; tetraplegia
urodynamics
Additional relevant MeSH terms:
Layout table for MeSH terms
Spinal Cord Injuries
Wounds and Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System