Transcutaneous Tibial Nerve Stimulation for Spinal Cord Injury Neurogenic Bladder

NCT04350359 | Recruiting DMC FDA Device

• 1 other identifier: HSC-MS-19-0756
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine if electric stimulation to the leg, called transcutaneous tibial nerve stimulation (TTNS), can improve bladder outcomes in acute spinal cord injury.

Conditions

Spinal Cord Injuries

Keywords

electric stimulation; SCI; spinal cord injury; neurogenic bladder

Outcome Measures

Primary Outcomes (7)

• Maintained bladder capacity as assessed by the Urodynamics study measured in ml

  we expect bladder capacity to be maintained in those with effective TTNS

  Baseline

• Maintained bladder capacity as assessed by the Urodynamics study measured in ml

  we expect bladder capacity to be maintained in those with effective TTNS

  4 months post SCI

• Prolonged sensation with bladder filling as assessed by the Urodynamics study measured in ml

  Evidence of TTNS mechanism expected in those with effective TTNS

  Baseline

• Prolonged sensation with bladder filling as assessed by the Urodynamics study measured in ml

  Evidence of TTNS mechanism expected in those with effective TTNS

  4 months post SCI

• Prolonged sensation with bladder filling as assessed by the Urodynamics study measured in ml

  Evidence of TTNS mechanism expected in those with effective TTNS

  1 year post SCI

• Change in bladder pathology from baseline presence of detrusor overactivity and DSD as assessed by the urodynamics study at 4 months.

  Reduced bladder pathology (presence of detrusor overactivity and DSD) in those with effective bladder neuromodulation based on change in urodynamic studies at baseline and 4-months

  Baseline, 4 months

• Change in bladder pathology from 4 month presence of detrusor overactivity and DSD as assessed by the urodynamics study at 1 year post SCI.

  Reduced bladder pathology (presence of detrusor overactivity and DSD) in those with effective bladder neuromodulation based on the change in urodynamic studies at 4 months and 1-year

  4 months and 1 year post SCI

Secondary Outcomes (3)

• Evidence of improved quality of life in those with effective bladder neuromodulation based on Incontinence Quality of Life (I-QOL) survey

  At discharge which could be up to 4 week from admission, 4-months post injury and at 1 year post injury.

• Evidence of improved quality of life in those with effective bladder neuromodulation based on Neurogenic Bladder Symptom Score (NBSS)

  Prior to discharge which could be up to 4 weeks from admission, monthly until 1 year post injury.

• Evidence of improved quality of life in those with effective bladder neuromodulation based on frequency of catheterization and voiding volumes

  2 days at the end of each month for 1 year.

Study Arms (3)

Variable-dose TTNS Protocol 5 x week

ACTIVE COMPARATOR

TTNS protocol: Electrodes 2 inch by 2 inch will be placed according to anatomic landmarks, with the negative electrode behind the internal malleolus and the positive electrode 10cm superior to the negative electrode, verified with rhythmic flexion of the toes secondary to stimulation of the flexor digitorum and hallicus brevis. The intensity level will be set to the amperage immediately under the threshold for motor contraction. If there is no contraction seen, patients will be excluded. In addition, if the patient perceives pain, the intensity will be lowered until comfortable. Stimulation frequency of 20 Hz and pulse width of 200ms in continuous mode will be used. All participants will be instructed to use the device for 30 minutes, 5 days per week for the first 4 months post-sci.

Device: Variable-dose TTNS Protocol 5 x week

Fixed-dose TTNS protocol

ACTIVE COMPARATOR

Fixed-dose protocol: Toe flexion will be attempted, as in the TTNS protocol. Then the stimulation will be reduced to 1 mA for 30 minutes. Both variable-dose TTNS and fixed-dose TTNS protocol participants will be instructed to use the device for 30 minutes, 5 days per week.

Device: Fixed-dose TTNS Protocol

Variable-dose TTNS Protocol 2 x week

ACTIVE COMPARATOR

At the 4 month CMG, subjects initially randomized into the variable dose protocol of 2 x weekly will start doing so for the remainder of the study.

Device: Variable-dose TTNS Protocol 2 x week

Interventions

Variable-dose TTNS Protocol 5 x week DEVICE

Electrodes 2 inch by 2 inch will be placed according to anatomic landmarks, with the negative electrode behind the internal malleolus and the positive electrode 10cm superior to the negative electrode, verified with rhythmic flexion of the toes secondary to stimulation of the flexor digitorum and hallicus brevis. The intensity level will be set to the amperage immediately under the threshold for motor contraction. If there is no contraction seen, patients will be excluded. In addition, if the patient perceives pain, the intensity will be lowered until comfortable. Stimulation frequency of 20 Hz and pulse width of 200ms in continuous mode will be used.

Variable-dose TTNS Protocol 5 x week

Fixed-dose TTNS Protocol DEVICE

Toe flexion will be attempted, as in the TTNS protocol. Then the stimulation will be reduced to 1 mA for 30 minutes. This will continue at 5x weekly until 1-year post-injury.

Fixed-dose TTNS protocol

Variable-dose TTNS Protocol 2 x week DEVICE

At the 4 month CMG, subjects initially randomized into the variable dose protocol of 2 x weekly will start doing so for the remainder of the study.

Variable-dose TTNS Protocol 2 x week

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• Traumatic or non-traumatic SCI
• Admitted to inpatient rehabilitation within 6 weeks
• T9 level of injury and above who are at greatest risk of morbid NGB
• Regionally located to allow follow-up
• English or Spanish speaking

You may not qualify if:

• History of genitourinary diagnoses (i.e. prostate hypertrophy, overactive bladder, cancer, etc.)
• History of central nervous system disorder (i.e. prior SCI, stroke, brain injury, Parkinson's disease, MS, etc.)
• History of peripheral neuropathy
• pre-SCI symptoms of peripheral neuropathy (numbness and/or tingling in feet, sharp/jabbing/burning pain in feet, sensitivity to touch, lack of coordination, muscle weakness, etc.)
• Pregnancy
• Known injury to the lumbosacral spinal cord or plexus, or pelvis with associated neuropathy
• concern for tibial nerve pathway injury
• absence of toe flexion or autonomic dysreflexia during electric stimulation test
• Potential for progressive SCI including neurodegenerative SCI, ALS, cancer myelopathy, Multiple sclerosis, transverse myelitis

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• MedStar National Rehabilitation Network: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

MedStar National Rehabilitation Hospital

Washington D.C., District of Columbia, 20010, United States

RECRUITING

TIRR Memorial Hermann Research Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (28)

• Ackery A, Tator C, Krassioukov A. A global perspective on spinal cord injury epidemiology. J Neurotrauma. 2004 Oct;21(10):1355-70. doi: 10.1089/neu.2004.21.1355.

  PMID: 15672627 BACKGROUND

• Weld KJ, Dmochowski RR. Association of level of injury and bladder behavior in patients with post-traumatic spinal cord injury. Urology. 2000 Apr;55(4):490-4. doi: 10.1016/s0090-4295(99)00553-1.

  PMID: 10736489 BACKGROUND

• Stohrer M, Blok B, Castro-Diaz D, Chartier-Kastler E, Del Popolo G, Kramer G, Pannek J, Radziszewski P, Wyndaele JJ. EAU guidelines on neurogenic lower urinary tract dysfunction. Eur Urol. 2009 Jul;56(1):81-8. doi: 10.1016/j.eururo.2009.04.028. Epub 2009 Apr 21.

  PMID: 19403235 BACKGROUND

• Anderson KD. Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma. 2004 Oct;21(10):1371-83. doi: 10.1089/neu.2004.21.1371.

  PMID: 15672628 BACKGROUND

• Chaabane W, Guillotreau J, Castel-Lacanal E, Abu-Anz S, De Boissezon X, Malavaud B, Marque P, Sarramon JP, Rischmann P, Game X. Sacral neuromodulation for treating neurogenic bladder dysfunction: clinical and urodynamic study. Neurourol Urodyn. 2011 Apr;30(4):547-50. doi: 10.1002/nau.21009.

  PMID: 21488095 BACKGROUND

• Chen G, Liao L, Li Y. The possible role of percutaneous tibial nerve stimulation using adhesive skin surface electrodes in patients with neurogenic detrusor overactivity secondary to spinal cord injury. Int Urol Nephrol. 2015 Mar;47(3):451-5. doi: 10.1007/s11255-015-0911-6. Epub 2015 Jan 22.

  PMID: 25609546 BACKGROUND

• del Popolo G, Mencarini M, Nelli F, Lazzeri M. Controversy over the pharmacological treatments of storage symptoms in spinal cord injury patients: a literature overview. Spinal Cord. 2012 Jan;50(1):8-13. doi: 10.1038/sc.2011.110. Epub 2011 Nov 1.

  PMID: 22042300 BACKGROUND

• Canbaz Kabay S, Kabay S, Mestan E, Cetiner M, Ayas S, Sevim M, Ozden H, Karaman HO. Long term sustained therapeutic effects of percutaneous posterior tibial nerve stimulation treatment of neurogenic overactive bladder in multiple sclerosis patients: 12-months results. Neurourol Urodyn. 2017 Jan;36(1):104-110. doi: 10.1002/nau.22868. Epub 2015 Sep 9.

  PMID: 26352904 BACKGROUND

• Sirls ER, Killinger KA, Boura JA, Peters KM. Percutaneous Tibial Nerve Stimulation in the Office Setting: Real-world Experience of Over 100 Patients. Urology. 2018 Mar;113:34-39. doi: 10.1016/j.urology.2017.11.026. Epub 2017 Nov 28.

  PMID: 29196071 BACKGROUND

• Fougere RJ, Currie KD, Nigro MK, Stothers L, Rapoport D, Krassioukov AV. Reduction in Bladder-Related Autonomic Dysreflexia after OnabotulinumtoxinA Treatment in Spinal Cord Injury. J Neurotrauma. 2016 Sep 15;33(18):1651-7. doi: 10.1089/neu.2015.4278. Epub 2016 Apr 13.

  PMID: 26980078 BACKGROUND

• Sievert KD, Amend B, Gakis G, Toomey P, Badke A, Kaps HP, Stenzl A. Early sacral neuromodulation prevents urinary incontinence after complete spinal cord injury. Ann Neurol. 2010 Jan;67(1):74-84. doi: 10.1002/ana.21814.

  PMID: 20186953 BACKGROUND

• de Seze M, Raibaut P, Gallien P, Even-Schneider A, Denys P, Bonniaud V, Game X, Amarenco G. Transcutaneous posterior tibial nerve stimulation for treatment of the overactive bladder syndrome in multiple sclerosis: results of a multicenter prospective study. Neurourol Urodyn. 2011 Mar;30(3):306-11. doi: 10.1002/nau.20958. Epub 2011 Feb 8.

  PMID: 21305588 BACKGROUND

• McDonald JW 3rd, Sadowsky CL, Stampas A. The changing field of rehabilitation: optimizing spontaneous regeneration and functional recovery. Handb Clin Neurol. 2012;109:317-36. doi: 10.1016/B978-0-444-52137-8.00020-6.

  PMID: 23098722 BACKGROUND

• Stampas A, Tansey KE. Spinal cord injury medicine and rehabilitation. Semin Neurol. 2014 Nov;34(5):524-33. doi: 10.1055/s-0034-1396006. Epub 2014 Dec 17.

  PMID: 25520024 BACKGROUND

• Stampas A, York HS, O'Dell MW. Is the Routine Use of a Functional Electrical Stimulation Cycle for Lower Limb Movement Standard of Care for Acute Spinal Cord Injury Rehabilitation? PM R. 2017 May;9(5):521-528. doi: 10.1016/j.pmrj.2017.03.005. No abstract available.

  PMID: 28526124 BACKGROUND

• Stampas A, Korupolu R, Zhu L, Smith CP, Gustafson K. Safety, Feasibility, and Efficacy of Transcutaneous Tibial Nerve Stimulation in Acute Spinal Cord Injury Neurogenic Bladder: A Randomized Control Pilot Trial. Neuromodulation. 2019 Aug;22(6):716-722. doi: 10.1111/ner.12855. Epub 2018 Oct 3.

  PMID: 30284350 BACKGROUND

• Sanford MT, Suskind AM. Neuromodulation in neurogenic bladder. Transl Androl Urol. 2016 Feb;5(1):117-26. doi: 10.3978/j.issn.2223-4683.2015.12.01.

  PMID: 26904417 BACKGROUND

• Stampas A, Gustafson K, Korupolu R, Smith C, Zhu L, Li S. Bladder Neuromodulation in Acute Spinal Cord Injury via Transcutaneous Tibial Nerve Stimulation: Cystometrogram and Autonomic Nervous System Evidence From a Randomized Control Pilot Trial. Front Neurosci. 2019 Feb 19;13:119. doi: 10.3389/fnins.2019.00119. eCollection 2019.

  PMID: 30837835 BACKGROUND

• Finazzi Agro E, Campagna A, Sciobica F, Petta F, Germani S, Zuccala A, Miano R. Posterior tibial nerve stimulation: is the once-a-week protocol the best option? Minerva Urol Nefrol. 2005 Jun;57(2):119-23. English, Italian.

  PMID: 15951736 BACKGROUND

• Manriquez V, Guzman R, Naser M, Aguilera A, Narvaez S, Castro A, Swift S, Digesu GA. Transcutaneous posterior tibial nerve stimulation versus extended release oxybutynin in overactive bladder patients. A prospective randomized trial. Eur J Obstet Gynecol Reprod Biol. 2016 Jan;196:6-10. doi: 10.1016/j.ejogrb.2015.09.020. Epub 2015 Oct 20.

  PMID: 26645117 BACKGROUND

• Gaziev G, Topazio L, Iacovelli V, Asimakopoulos A, Di Santo A, De Nunzio C, Finazzi-Agro E. Percutaneous Tibial Nerve Stimulation (PTNS) efficacy in the treatment of lower urinary tract dysfunctions: a systematic review. BMC Urol. 2013 Nov 25;13:61. doi: 10.1186/1471-2490-13-61.

  PMID: 24274173 BACKGROUND

• Dubeau CE. The aging lower urinary tract. J Urol. 2006 Mar;175(3 Pt 2):S11-5. doi: 10.1016/S0022-5347(05)00311-3.

  PMID: 16458733 BACKGROUND

• Welk B, Lenherr S, Elliott S, Stoffel J, Presson AP, Zhang C, Myers JB. The Neurogenic Bladder Symptom Score (NBSS): a secondary assessment of its validity, reliability among people with a spinal cord injury. Spinal Cord. 2018 Mar;56(3):259-264. doi: 10.1038/s41393-017-0028-0. Epub 2017 Nov 29.

  PMID: 29184133 BACKGROUND

• Schurch B, Denys P, Kozma CM, Reese PR, Slaton T, Barron R. Reliability and validity of the Incontinence Quality of Life questionnaire in patients with neurogenic urinary incontinence. Arch Phys Med Rehabil. 2007 May;88(5):646-52. doi: 10.1016/j.apmr.2007.02.009.

  PMID: 17466735 BACKGROUND

• Bothig R, Fiebag K, Thietje R, Faschingbauer M, Hirschfeld S. Morbidity of urinary tract infection after urodynamic examination of hospitalized SCI patients: the impact of bladder management. Spinal Cord. 2013 Jan;51(1):70-3. doi: 10.1038/sc.2012.107. Epub 2012 Sep 11.

  PMID: 22964752 BACKGROUND

• Pannek J, Nehiba M. Morbidity of urodynamic testing in patients with spinal cord injury: is antibiotic prophylaxis necessary? Spinal Cord. 2007 Dec;45(12):771-4. doi: 10.1038/sj.sc.3102114. Epub 2007 Aug 21.

  PMID: 17710104 BACKGROUND

• Street JT, Noonan VK, Cheung A, Fisher CG, Dvorak MF. Incidence of acute care adverse events and long-term health-related quality of life in patients with TSCI. Spine J. 2015 May 1;15(5):923-32. doi: 10.1016/j.spinee.2013.06.051. Epub 2013 Aug 24.

  PMID: 23981816 BACKGROUND

• Montgomerie JZ. Infections in patients with spinal cord injuries. Clin Infect Dis. 1997 Dec;25(6):1285-90; quiz 1291-2. doi: 10.1086/516144. No abstract available.

  PMID: 9431366 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries; Urinary Bladder, Neurogenic

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Neurologic Manifestations; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Argyrios Stampas, MD

  UTHealth and TIRR Mermorial Hermann

  PRINCIPAL INVESTIGATOR

• Suzanne Groah, MD

  MedStar National Rehabilitation Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Argyrios Stampas, MD

CONTACT

713-797-5938; argyrios.stampas@uth.tmc.edu

Jacqueline Waterson

CONTACT

(713) 797-5765; Jacqueline.b.waterson@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Subjects will be randomized to either Variable or fixed-dose (2:1) using a block size of 6 and stratified based on complete/incomplete SCI to ensure the equal allocation of the most severely injured in the two groups. The PI and investigators will be blinded to randomization and treatment allocation, managed by the research assistant.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Spinal Cord Injury Medicine Research Director

Model Details: A prospective, double-blinded, randomized trial.

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: April 17, 2020
• Study Start: June 8, 2020
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)