Transcutaneous Tibial Nerve Stimulation for Spinal Cord Injury Neurogenic Bladder

Spinal Cord Injuries Clinical Trial

— TTNS1yr  

Official title:

Transcutaneous Tibial Nerve Stimulation for Spinal Cord Injury Neurogenic Bladder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04350359
• Other study ID #: HSC-MS-19-0756
• Status: Recruiting
• Phase: N/A
• Start date: June 8, 2020
• Est. completion date: December 1, 2025

Study information

• Verified date: June 2023
• Source: The University of Texas Health Science Center, Houston
• Contact: Argyrios Stampas, MD
• Phone: 713-797-5938
• Email: argyrios.stampas[@]uth.tmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The purpose of this study is to see how well TTNS works at preventing incontinence in people with paraplegia from SCI that perform intermittent catheterization to empty their bladder. This study will compare the effectiveness of TTNS at 2 doses, fixed-dose and variable-dose. It will also evaluate the frequency of use, 2 days weekly compared to 5 days weekly.

Based on our pilot trials, tibial nerve stimulation protocols use submotor current intensity with a duration of 200 µs and a frequency of 20Hz. The experimental group will use a submotor "variable dose." The fixed-dose group will use submotor at current intensity at 1mA and designated as "fixed-dose."

TTNS will be used 5 days weekly, per our pilot trial. At 4-months post-SCI, the subject will be instructed to switch to 2x daily if he or she was randomized into the variable dose group of 2 days weekly and thus continue to doing so for the remainder of study participation. Because there is support in the literature for reduced doses of tibial nerve stimulation required for maintenance (1-3x weekly), the RCT includes this frequency comparison arm. All subjects will continue for 1-year post-SCI.

Additionally, we are collecting surveys to help identify characteristics of people (resilience and confidence) and adherence to medication and TTNS use throughout the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18-75 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Urinary Bladder, Neurogenic
• Wounds and Injuries

Intervention

Device:
• Variable-dose TTNS Protocol 5 x week
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.
• Fixed-dose TTNS Protocol
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.
• Variable-dose TTNS Protocol 2 x week
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.

Locations

Country	Name	City	State
United States	TIRR Memorial Hermann Research Center	Houston	Texas
United States	MedStar National Rehabilitation Hospital	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston	MedStar National Rehabilitation Network, The Methodist Hospital Research Institute

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Evidence of improved quality of life in those with effective bladder neuromodulation based on Incontinence Quality of Life (I-QOL) survey	Comparing I-QOL upon discharge from rehabilitation, 4-months post-injury and 1-year post-injury using incontinence QOL (I-QOL) survey, between and within both arms of the study	At discharge which could be up to 4 week from admission, 4-months post injury and at 1 year post injury.
Secondary	Evidence of improved quality of life in those with effective bladder neuromodulation based on Neurogenic Bladder Symptom Score (NBSS)	Changes in Neurogenic Bladder Symptom Scores. The total score can range from 0 (no symptoms at all) to 74 (maximum symptoms) where a lower score indicates a better outcome.	Prior to discharge which could be up to 4 weeks from admission, monthly until 1 year post injury.
Secondary	Evidence of improved quality of life in those with effective bladder neuromodulation based on frequency of catheterization and voiding volumes	Maintaining frequency of catheterization (count per day) and volumes per void (ml per collection)	2 days at the end of each month for 1 year.