TTNS for Neurogenic Bladder

(TTNS1yr Trial)

Recruiting at 1 trial location

Overseen By Argyrios Stampas, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Genitourinary diagnoses, CNS disorder, Peripheral neuropathy, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 4 months

120 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

What data supports the effectiveness of the treatment Transcutaneous Tibial Nerve Stimulation (TTNS) for neurogenic bladder?

Research shows that Transcutaneous Tibial Nerve Stimulation (TTNS) is effective for various bladder issues, like overactive bladder and bladder pain syndrome, suggesting it could help with neurogenic bladder too. ^{1 2 3 4 5}

Is transcutaneous tibial nerve stimulation (TTNS) safe for humans?

Transcutaneous tibial nerve stimulation (TTNS) is considered a safe treatment for conditions like overactive bladder in adults, as indicated by studies comparing it to other therapies. ^{1 2 4 6 7}

How does the treatment TTNS for neurogenic bladder differ from other treatments?

TTNS (Transcutaneous Tibial Nerve Stimulation) is unique because it uses electrical stimulation applied through the skin to target the tibial nerve, offering a non-invasive alternative to other methods like PTNS (Percutaneous Tibial Nerve Stimulation), which requires needle insertion. This makes TTNS a more comfortable and accessible option for patients. ^{1 2 3 5 8}

Research Team

Suzanne Groah, MD,MSPH

Principal Investigator

MedStar National Rehabilitation Hospital

Argyrios Stampas, MD

Principal Investigator

UTHealth and TIRR Mermorial Hermann

Eligibility Criteria

This trial is for adults aged 18-75 with a spinal cord injury at T9 level or above, who are within 6 weeks of inpatient rehabilitation and can follow up regionally. Participants must speak English or Spanish. Excluded are those with tibial nerve damage, toe flexion issues during tests, pregnancy, pre-injury neuropathy symptoms, progressive SCI conditions like ALS or MS, genitourinary disorders history, CNS disorders history.

Inclusion Criteria

My spinal injury is above the T9 level and I'm at high risk of severe bladder problems.

I have a spinal cord injury.

I am between 18 and 75 years old.

Exclusion Criteria

I have had issues with my urinary system, like an enlarged prostate or bladder problems.

I have had nerve damage in my hands or feet.

I had symptoms like numbness or pain in my feet before my spinal cord injury.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcutaneous tibial nerve stimulation (TTNS) for bladder outcomes improvement, with variable and fixed-dose protocols

4 months

5 visits per week (in-person)

Maintenance Treatment

Participants in the variable-dose group switch to 2x daily TTNS for the remainder of the study

8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including urodynamics studies and quality of life assessments

1 year post-SCI

Treatment Details

Interventions

• Transcutaneous Tibial Nerve Stimulation

Trial Overview The study examines if transcutaneous tibial nerve stimulation (TTNS), an electric leg stimulation therapy given either five times a week or twice a week at variable doses or as a fixed dose protocol can improve bladder control in patients with recent acute spinal cord injuries.

Participant Groups

Group I: Variable-dose TTNS Protocol 5 x week Active Control 1 Intervention

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.

Group II: Fixed-dose TTNS protocol Active Control 1 Intervention

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.

Group III: Variable-dose TTNS Protocol 2 x week Active Control 1 Intervention

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.

Transcutaneous Tibial Nerve Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as TTNS for:

• Overactive bladder
• Urinary frequency
• Urinary urgency
• Urge incontinence

Approved in European Union as TTNS for:

• Overactive bladder
• Urinary frequency
• Urinary urgency
• Urge incontinence

Approved in Canada as TTNS for:

• Overactive bladder
• Urinary frequency
• Urinary urgency
• Urge incontinence

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

MedStar National Rehabilitation Network

Collaborator

Trials

15

Recruited

4,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Findings from Research

In a study of 51 patients with lower urinary tract symptoms, bilateral transcutaneous tibial nerve stimulation (TTNS) significantly improved bladder function, increasing the filling volume at the first desire to void by 54 mL and the maximum cystometric capacity by 41 mL compared to placebo.

TTNS was particularly effective in patients without anatomical pathologies, as those with pathological postvoid residual volumes experienced a 76 mL increase in median micturition volume, indicating its potential as a treatment for urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Crossover-Controlled Evaluation of Simultaneous Bilateral Transcutaneous Electrostimulation of the Posterior Tibial Nerve During Urodynamic Studies in Patients With Lower Urinary Tract Symptoms. Girtner, F., Fritsche, HM., Zeman, F., et al.[2022]

Transcutaneous tibial nerve stimulation (TTNS) is as effective as percutaneous tibial nerve stimulation (PTNS) in treating overactive bladder, based on a systematic review of 4 trials involving 142 patients.

TTNS showed a total complication rate of only 2.1% with no adverse events reported, indicating a potentially safer option compared to PTNS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment for overactive bladder: A meta-analysis of transcutaneous tibial nerve stimulation versus percutaneous tibial nerve stimulation. Yang, DY., Zhao, LN., Qiu, MX.[2023]

Stimulation of the saphenous nerve (SAFN) at a frequency of 20 Hz significantly reduced bladder contraction rates by about 53.8% and increased bladder capacity by approximately 145.8% in a study involving 26 anesthetized rats.

These results suggest that SAFN stimulation may evoke a bladder-inhibitory reflex, indicating a potential new pathway for treating overactive bladder, although further research is needed to explore its clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency-dependent inhibition of bladder function by saphenous nerve stimulation in anesthetized rats. Moazzam, Z., Yoo, PB.[2019]

Transcutaneous tibial nerve stimulation (TTNS) significantly reduced daytime urinary frequency and nocturia in 16 female patients with bladder pain syndrome after 12 weeks of treatment, indicating its efficacy as a non-invasive therapy.

Patients also reported improved bladder capacity and reduced pain levels, suggesting that TTNS can be a viable alternative to invasive treatments for bladder pain syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of transcutaneous tibial nerve stimulation in the treatment of bladder pain syndrome. Alkis, O., Aras, B., Sevim, M., et al.[2023]

Transcutaneous electrical nerve stimulation (TTNS) is more comfortable for patients compared to percutaneous electrical nerve stimulation (PTNS) while both methods show similar effectiveness in treating overactive bladder (OAB) with urinary incontinence (UI).

Combining TTNS or PTNS with other treatments, such as medications or exercises, leads to greater improvements in reducing urinary incontinence and enhancing quality of life, based on a systematic review of 259 studies, with 19 meeting the inclusion criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous versus Transcutaneous Electrical Stimulation of the Posterior Tibial Nerve in Idiopathic Overactive Bladder Syndrome with Urinary Incontinence in Adults: A Systematic Review. Agost-González, A., Escobio-Prieto, I., Pareja-Leal, AM., et al.[2021]

The study aims to evaluate the efficacy of transcutaneous tibial nerve stimulation (TTNS) for treating idiopathic overactive bladder syndrome in children aged 5 to 12 years, comparing it to a sham therapy over 12 weeks.

This is the first randomized controlled trial to assess TTNS in a pediatric population, with the hypothesis that TTNS will be as effective as percutaneous tibial nerve stimulation (PTNS), providing important insights into non-invasive treatment options for overactive bladder in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of transcutaneous tibial nerve stimulation (TTNS) versus sham therapy (part I) and TTNS versus percutaneous tibial nerve stimulation (PTNS) (part II) on the short term in children with the idiopathic overactive bladder syndrome: protocol for part I of the twofold double-blinded randomized controlled TaPaS trial. Ghijselings, L., Renson, C., Van de Walle, J., et al.[2021]

In a study involving 8 patients with refractory overactive bladder, implant-driven tibial nerve stimulation (PTNS) demonstrated feasibility and safety, with significant improvements in voiding and quality of life at 3 and 6 months follow-up.

Five out of eight patients achieved a ≥50% reduction in incontinence episodes at 3 months, indicating that PTNS can effectively reduce symptoms of overactive bladder without serious complications like infection or dislocation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implant-Driven Tibial Nerve Stimulation in the Treatment of Refractory Overactive Bladder Syndrome: 12-Month Follow-up. van der Pal, F., van Balken, MR., Heesakkers, JP., et al.[2022]

Posterior tibial nerve stimulation (PTNS) shows promise as an effective treatment for overactive bladder (OAB) in women, with success rates reported between 54% and 93% in good quality studies.

However, the current literature is limited, with only 4 out of 17 studies meeting high-quality criteria, indicating a need for more comprehensive research to fully evaluate PTNS's efficacy and support its widespread use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of posterior tibial nerve stimulation for the treatment of overactive bladder in women: a systematic review. Levin, PJ., Wu, JM., Kawasaki, A., et al.[2021]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Randomized Crossover-Controlled Evaluation of Simultaneous Bilateral Transcutaneous Electrostimulation of the Posterior Tibial Nerve During Urodynamic Studies in Patients With Lower Urinary Tract Symptoms. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment for overactive bladder: A meta-analysis of transcutaneous tibial nerve stimulation versus percutaneous tibial nerve stimulation. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Frequency-dependent inhibition of bladder function by saphenous nerve stimulation in anesthetized rats. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy of transcutaneous tibial nerve stimulation in the treatment of bladder pain syndrome. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Percutaneous versus Transcutaneous Electrical Stimulation of the Posterior Tibial Nerve in Idiopathic Overactive Bladder Syndrome with Urinary Incontinence in Adults: A Systematic Review. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy of transcutaneous tibial nerve stimulation (TTNS) versus sham therapy (part I) and TTNS versus percutaneous tibial nerve stimulation (PTNS) (part II) on the short term in children with the idiopathic overactive bladder syndrome: protocol for part I of the twofold double-blinded randomized controlled TaPaS trial. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Implant-Driven Tibial Nerve Stimulation in the Treatment of Refractory Overactive Bladder Syndrome: 12-Month Follow-up. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The efficacy of posterior tibial nerve stimulation for the treatment of overactive bladder in women: a systematic review. [2021]