Neuromodulation for Bowel Incontinence

(TNT Trial)

Not currently recruiting at 1 trial location

Overseen By Satish Rao, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Augusta University

Must not be taking: Opioids

Disqualifiers: Severe diarrhea, Active depression, Neurologic diseases, Severe cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test a new, non-invasive treatment called Translumbosacral Neuromodulation Therapy (TNT) for individuals with fecal incontinence (FI). FI, a condition where individuals struggle to control bowel movements, affects daily life for many, particularly women and the elderly. The trial will assess TNT's effectiveness by comparing different treatment doses and a sham treatment to determine the most effective approach. Suitable participants have experienced FI episodes for at least six months and report at least one episode per week. The goal is to find a safe and effective method to improve bowel control and enhance the quality of life for those affected by FI. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for FI.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on opioids, you cannot participate in the trial.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on opioids.

What prior data suggests that Translumbosacral Neuromodulation Therapy (TNT) is safe for treating fecal incontinence?

Previous studies have shown that Translumbosacral Neuromodulation Therapy (TNT) is safe for treating fecal incontinence. Research indicates that TNT, particularly at a frequency of 1 Hz, greatly reduces symptoms and is well-tolerated by patients. These studies suggest that TNT offers a non-invasive and low-risk option. Reports demonstrate that TNT improves nerve function in the anal area without causing significant side effects. Overall, these studies support TNT as a safe treatment option for managing fecal incontinence. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Translumbosacral Neuromodulation Therapy (TNT) for bowel incontinence because it offers a non-invasive alternative to current treatments like medications or surgical options. TNT uses magnetic coils to deliver targeted stimulations to the lumbar and sacral regions, potentially enhancing nerve function and bowel control without the need for drugs or surgical intervention. Unlike existing treatments that may take time to show results, TNT could offer quicker improvements by directly stimulating the nerves involved in bowel function. Different arms of TNT, such as the 1 Hz 2400 and 3600 stimulation treatments, allow researchers to explore the most effective stimulation intensity and duration, paving the way for personalized therapy options.

What evidence suggests that Translumbosacral Neuromodulation Therapy (TNT) might be an effective treatment for fecal incontinence?

Research has shown that Translumbosacral Neuromodulation Therapy (TNT) can greatly improve symptoms of fecal incontinence (FI). Previous studies found that using TNT at a 1 Hz frequency improves communication between the gut and brain and strengthens the anal sphincter. In this trial, participants will receive either the active TNT treatment or a Sham TNT treatment. Specifically, patients in earlier studies who received active TNT experienced fewer FI episodes, with significant improvements compared to a placebo treatment. This suggests that TNT helps regain control over bowel movements by enhancing signals between the brain and pelvic floor muscles. Overall, TNT offers a promising new option for those dealing with FI. ^{1 2 4 5 6}

Who Is on the Research Team?

Satish Rao, MD,PhD

Principal Investigator

Augusta University

Are You a Good Fit for This Trial?

This trial is for adults who've had bowel incontinence for at least 6 months, with weekly episodes. They must not have mucosal diseases, be on opioids, or have a range of other conditions like Crohn's disease, severe heart issues, metal implants near the treatment area, pacemakers, or certain past surgeries.

Inclusion Criteria

I have had at least one episode of incontinence per week.

No mucosal disease (colonoscopy + biopsy)

I have had recurring episodes of fecal incontinence for 6 months.

Exclusion Criteria

You are pregnant.

I have a condition where part of my rectum sticks out of my anus.

I have been diagnosed with either ulcerative colitis or Crohn's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Translumbosacral Neuromodulation Therapy (TNT) with varying doses of magnetic stimulation to improve fecal incontinence

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

Long-term Follow-up

Assessment of the durability of treatment response and effects of TNT over an extended period

48 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sham TNT Therapy
• Translumbosacral Neuromodulation Therapy (TNT)

Trial Overview The study tests Translumbosacral Neuromodulation Therapy (TNT) against a sham (fake) therapy to see if TNT can improve bowel control by stimulating nerves with magnetic fields. It aims to find the best dose and understand how it works over short and long terms.

How Is the Trial Designed?

Group I: 1 Hz 2400 TNT Treatment Active Control 1 Intervention

Intervention: TNT treatment intervention with 2400 total stimulations with the magnetic coil..

Group II: 1 Hz 3600 TNT Treatment Active Control 1 Intervention

Intervention: TNT treatment intervention with 3600 total stimulations with the magnetic coil.

Group III: Sham TNT Treatment Placebo Group 1 Intervention

This arm will have the sham treatment session. First we will assess the motor threshold intensity described above. Next, a sham coil is placed on each of 4 regions (2 lumbar \& 2 sacral), and 600 stimulations will be given at each site in 2 trains, with a 5 minutes rest period between each site and 3 minutes between trains.

Who Is Running the Clinical Trial?

Augusta University

Lead Sponsor

Trials

219

Recruited

85,900+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 16 patients with severe fecal incontinence, percutaneous tibial nerve stimulation significantly improved fecal continence, with the Wexner score decreasing from 13.2 to 9 after the first treatment phase.

After six months without treatment, 5 out of 16 patients maintained good continence, indicating that the benefits of this minimally invasive therapy can be long-lasting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the use of posterior tibial nerve stimulation for the treatment of fecal incontinence: preliminary results of a prospective study. de la Portilla, F., Rada, R., Vega, J., et al.[2019]

Translumbosacral neuromodulation therapy (TNT) significantly reduces fecal incontinence (FI) episodes in patients, with the 1 Hz frequency showing the highest responder rate of 91%, compared to 36% for 5 Hz and 55% for 15 Hz.

TNT not only improved FI symptoms but also enhanced anorectal neuropathy and physiological function, indicating a mechanistic improvement, and it was found to be safe with no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translumbosacral Neuromodulation Therapy for Fecal Incontinence: A Randomized Frequency Response Trial. Rao, SSC., Xiang, X., Sharma, A., et al.[2023]

Sacral neuromodulation (SNM) has shown a high success rate of 84.2% in treating neurogenic lower urinary tract dysfunctions (nLUTD) based on a meta-analysis of 24 studies involving 428 patients, indicating its effectiveness for these conditions.

The procedure is generally safe, with common adverse events occurring at low rates (e.g., 4.7% for loss of effectiveness and 3.6% for infection), but the authors note the need for more rigorous studies to confirm these findings and address limitations in the current research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Literature Review and Meta-Analysis of Sacral Neuromodulation (SNM) in Patients with Neurogenic Lower Urinary Tract Dysfunction (nLUTD): Over 20 Years' Experience and Future Directions. van Ophoven, A., Engelberg, S., Lilley, H., et al.[2021]

The NeuromOdulaTion for Accidental Bowel Leakage trial is designed to evaluate the effectiveness of percutaneous tibial nerve stimulation (PTNS) compared to a sham treatment in women with persistent fecal incontinence, involving 165 participants to ensure robust statistical power.

The study aims to provide high-level evidence on the efficacy of PTNS as a second-line treatment, with a focus on improving bowel control and quality of life over 12 weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of a Randomized Controlled Trial of Percutaneous Posterior Tibial Nerve Stimulation for the Treatment of Refractory Fecal Incontinence in Women: The NeurOmodulaTion for Accidental Bowel Leakage Study. Zyczynski, HM., Arya, LA., Lukacz, ES., et al.[2022]

Sacral neuromodulation (SNM) is increasingly recognized as a promising treatment for neurogenic lower urinary tract dysfunction (NLUTD), particularly in patients with incomplete spinal cord injuries and multiple sclerosis, although most studies have methodological limitations and lack standardized success definitions.

Recent technological advancements aim to overcome barriers to SNM, such as MRI incompatibility and issues with the size and battery life of the implantable pulse generator, suggesting that this therapy could become more accessible and effective in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for sacral neuromodulation in patients with neurogenic lower urinary tract dysfunction? Averbeck, MA., Moreno-Palacios, J., Aparicio, A.[2021]

In a study of 20 patients with refractory fecal incontinence, percutaneous tibial nerve stimulation did not significantly improve incontinence scores after treatment, indicating limited efficacy for this therapy.

However, 68.4% of patients who subsequently received sacral nerve stimulation reported significant improvement in their incontinence scores, suggesting that sacral nerve stimulation is an effective second-line treatment for those who do not respond to tibial nerve stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of sacral nerve stimulation for fecal incontinence in patients refractory to percutaneous tibial nerve stimulation. Hotouras, A., Murphy, J., Thin, NN., et al.[2022]

Translumbosacral neuromodulation therapy (TNT) significantly improves symptoms of fecal incontinence (FI) by enhancing afferent ano-cortical signaling and efferent motor pathways, particularly at a frequency of 1 Hz, as shown in a study with 33 participants.

The 1 Hz frequency not only decreased latencies in neural signaling but also increased anal sphincter pressure and maximum tolerable volume, leading to a higher rate of symptom improvement compared to other frequencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Translumbosacral Neuromodulation Therapy on Gut and Brain Interactions and Anorectal Neuropathy in Fecal Incontinence: A Randomized Study. Rao, SSC., Yan, Y., Xiang, X., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9455260/

Translumbosacral Neuromodulation Therapy for Fecal ... Conclusions: TNT significantly improves FI symptoms in the short-term, and the 1 Hz frequency was overall better than 5 Hz and 15 Hz. Both anorectal ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03899181

Translumbosacral Neuromodulation for FI (TNT) Our approach is based on compelling pilot study which showed that TNT at 1 Hz frequency, significantly improved FI, by enhancing bidirectional gut- brain ...

3. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/tnt4fi

Translumbosacral Neuromodulation Therapy for Fecal ... This study is expected to improve fecal incontinence and increase scientific understanding of the condition and its treatment options. Preliminary results ...

4. journals.lww.com journals.lww.com/10.14309/01.ajg.0001131788.55565.5b

Official journal of the American College of Gastroenterology There was no change in the sham group. Mean FI episodes improved significantly (P < .001) in the active TNT groups with a higher responder rate (P < .001) ...

5. grantome.com grantome.com/grant/NIH/R01-DK121003-02

Translumbosacral Neuromodulation Therapy for Fecal ... Our approach is based on compelling preliminary study which showed that TNT at 1 Hz frequency, significantly improved FI, by enhancing bidirectional gut and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32740081/

Translumbosacral Neuromodulation Therapy for Fecal ... Results: Thirty-three patients with FI participated. FI episodes decreased significantly (∆ ±95% confidence interval, 4.2 ± 2.8 (1 Hz); 2 ± 1.7 ...