TTNS for Neurogenic Bladder

(TTNS1yr Trial)

Recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether transcutaneous tibial nerve stimulation (TTNS), which uses electric pulses on the leg, can improve bladder function in people with recent spinal cord injuries. Participants will use the TTNS device on either a fixed or variable schedule to determine which method is most effective. The trial seeks individuals who have experienced a spinal cord injury within the last six weeks and are facing bladder issues. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could enhance treatment options for bladder issues related to spinal cord injuries.

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 prior data suggests that transcutaneous tibial nerve stimulation (TTNS) is safe for improving bladder outcomes in acute spinal cord injury?

Research shows that transcutaneous tibial nerve stimulation (TTNS) is generally safe. Studies have found that TTNS can help manage bladder problems, especially in individuals with spinal cord injuries. Many participants report that TTNS is easy to tolerate and notice improvements in bladder function.

In one study involving people with multiple sclerosis, over 80% experienced reduced urgency and frequency in urination. Another study demonstrated that TTNS effectively reduces symptoms of an overactive bladder after 12 weeks of use.

Overall, these findings suggest that TTNS is a well-tolerated treatment with a good safety record. However, individual experiences can differ. Always consult a healthcare provider about potential risks and benefits before starting any new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Transcutaneous Tibial Nerve Stimulation (TTNS) protocols for neurogenic bladder because they offer a non-invasive alternative to current treatments, which often include medications like anticholinergics or invasive procedures such as catheterization. TTNS works by stimulating the tibial nerve through electrodes placed on the skin, potentially improving bladder control without the side effects associated with drugs. The study explores both variable-dose and fixed-dose protocols, aiming to find the most effective regimen. This approach could lead to more personalized and comfortable treatment options for patients with neurogenic bladder.

What evidence suggests that transcutaneous tibial nerve stimulation is effective for improving bladder outcomes in acute spinal cord injury?

Research shows that transcutaneous tibial nerve stimulation (TTNS) can significantly help with bladder problems. This trial will compare different TTNS protocols, including variable-dose and fixed-dose approaches. Studies have found that TTNS is as effective as medication for issues like frequent urination and waking up at night to use the bathroom. For individuals with spinal cord injuries, TTNS can aid in managing incontinence and enhance the sensation of needing to urinate. In some cases, TTNS has even enabled patients to discontinue certain medications. This treatment sends gentle electrical pulses to a nerve in the leg, helping to control bladder function. Early results are promising for using TTNS to improve bladder issues in people with spinal cord injuries. ^{6 7 8 9 10}

Who Is on the Research Team?

Suzanne Groah, MD,MSPH

Principal Investigator

MedStar National Rehabilitation Hospital

Argyrios Stampas, MD

Principal Investigator

UTHealth and TIRR Mermorial Hermann

Are You a Good Fit for This Trial?

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 was admitted to a rehab facility within the last 6 weeks.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28731583/

The effectiveness of transcutaneous tibial nerve stimulation ... Narrative review showed TTNS and antimuscarinic treatment were equally effective (four trials), TTNS provided greater benefit for OAB symptoms ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772973725007805

239 - Transcutaneous Tibial Nerve Stimulation in a ... TTNS significantly improved daily micturitions, nocturia, voided volume, and bladder sensation, with 17.9% of patients discontinuing medication reinforcing its ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04350359

Transcutaneous Tibial Nerve Stimulation for Spinal Cord ... The purpose of this study is to see how well TTNS works at preventing incontinence in people with paraplegia from SCI that perform intermittent ...

4. nature.com nature.com/articles/s41598-024-78492-2

Efficacy of the combination of transcutaneous tibial nerve ... Primary outcomes were changes from baseline in the lower urinary tract symptoms. The severity of symptoms and quality of life (QoL) were ...

5. bjui-journals.onlinelibrary.wiley.com bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.16081

transcutaneous tibial nerve stimulation for neurogenic ... The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7337720/

A randomized, controlled trial of transcutaneous tibial ... This randomized, sham-controlled clinical trial found that TTNS was not effective at improving bladder function among non-neurogenic and neurogenic bladder ...

7. auajournals.org auajournals.org/doi/10.1097/01.JU.0001110196.19418.44.13

PD39-13 PAST, PRESENT, AND FUTURE OF ... While tTNS has shown safety, feasibility, and efficacy for NB management in SCI, many questions remain before adopting this into usual care.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2772973724002741

Long term safety, continuation rates and subjective ... PTNS remains a safe treatment option for patients with refractory OAB with evidence of both subjective and objective improvement to most symptoms.

9. eurjmedres.biomedcentral.com eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-02262-z

Efficacy and safety of non-invasive low-frequency tibial nerve ... The TNS-01 device is effective and safe in relieving OAB symptoms after 12 weeks of stimulation. Trial registration number: NCT04999657.

10. urology.wisc.edu urology.wisc.edu/wp-content/uploads/2018/10/Gustafson-TTNS-for-SCI-Neuromodulation-2018.pdf

Safety, Feasibility, and Efficacy of Transcutaneous Tibial ... In a multicenter study of neurogenic bladder due to multi- ple sclerosis, TTNS improved urinary urgency in more than 80% of the subjects, reduced frequency, and ...