rTMS for Interstitial Cystitis

(IcBrainStim Trial)

Overseen By Larissa V Rodriguez, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University of Southern California

Disqualifiers: Neurological conditions, Auto-immune disorders, Cancer, Psychiatric disorders, Severe cardiac disease, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 1 week

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses magnetic pulses to stimulate the brain in women with chronic bladder pain. The goal is to reduce pain and muscle issues by improving brain function. The study will involve 50 women. Pulsed electromagnetic field (PEMF) therapy has been studied for its potential to reduce pain and improve quality of life in various conditions, including chronic pain syndromes.

Do I need to stop my current medications for the rTMS 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 or your doctor.

What data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for Interstitial Cystitis?

Research shows that rTMS, when used with standard drug therapies, can help reduce chronic pain in patients with Bladder Pain Syndrome/Interstitial Cystitis who do not respond to medication alone. It also suggests improvements in urinary symptoms and quality of life. ^{1 2 3 4 5}

Is rTMS generally safe for humans?

Research indicates that repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe for humans, as studies have evaluated its safety and tolerability in treating conditions like chronic neuropathic pain and bladder pain syndrome. ^{1 6 7 8 9}

How does rTMS treatment differ from other treatments for interstitial cystitis?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, which can help reduce pain and improve symptoms in interstitial cystitis. Unlike standard drug therapies, rTMS is non-invasive and targets the brain's dorsolateral prefrontal cortex to alleviate pain and improve quality of life. ^{1 2 6 7 10}

Research Team

Jason J Kutch, PhD

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for women over 18 with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) who've had urologic symptoms most of the time in the last 3 months. They must not have cancer, severe organ disease, major psychiatric disorders, ongoing neurological conditions affecting bladder or bowel, or be pregnant.

Inclusion Criteria

I am 18 years old or older.

I am female.

I have been diagnosed with interstitial cystitis/bladder pain syndrome for the last 3 months.

Exclusion Criteria

I have symptoms from a narrowed urethra.

I do not have conditions like seizures, chronic headaches, or pregnancy that prevent MRI or rTMS use.

You have severe mental health conditions right now.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high-frequency or sham rTMS treatment for 5 consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for changes in pain and brain/muscle activity

3 weeks

1 visit (in-person)

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)
• Sham Repetitive Transcranial Magnetic Stimulation (Sham-rTMS)

Trial Overview The study tests if non-invasive brain stimulation (rTMS) can reduce IC/BPS pain by targeting brain areas that control pelvic muscles. A sham procedure (Sham-rTMS), which mimics rTMS without active treatment, is used for comparison.

Participant Groups

Group I: High-frequency rTMS Active Control 1 Intervention

Intensity: rTMS treatment intensity determined using resting motor threshold (RMT). Treatment will be delivered at 80% of the RMT. Site of Stimulation: Region of supplementary motor area (SMA) that regulates pelvic floor muscle activity. This target is defined in Montreal Neurological Institute (MNI) Coordinates of X=-2, Y=-16, and Z=68 mm. Frequency: 10 Hz. Duration: 20 Trains, 10 second duration, 50 second inter-train interval. Total number of pulses per session: 2000. Total number of session: 5 (one session per day for 5 consecutive days).

Group II: Sham rTMS Placebo Group 1 Intervention

Identical to the High-frequency rTMS arm except delivered with an inert "sham" stimulation coil.

Repetitive Transcranial Magnetic Stimulation (rTMS) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as rTMS for:

• Depression
• Smoking cessation

Approved in European Union as rTMS for:

• Depression

Approved in Canada as rTMS for:

• Depression

Approved in Japan as rTMS for:

• Depression

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Findings from Research

In a study involving 15 patients with Bladder Pain Syndrome/Interstitial Cystitis, repetitive Transcranial Magnetic Stimulation (rTMS) significantly reduced chronic pelvic pain and improved urinary symptoms compared to sham treatment.

rTMS was found to enhance quality of life without any serious adverse events, indicating it is a safe and effective adjunct therapy for patients whose pain does not respond to standard drug treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for chronic neuropathic pain in patients with bladder pain syndrome/interstitial cystitis. Cervigni, M., Onesti, E., Ceccanti, M., et al.[2019]

In a study of 25 patients with refractory interstitial cystitis, sacral neuromodulation significantly improved symptoms, with 17 patients qualifying for permanent implantation after showing at least 50% improvement in key measures.

At an average follow-up of 14 months, patients experienced substantial reductions in daytime frequency (from 17.1 to 8.7), nocturia (from 4.5 to 1.1), and average pain (from 5.8 to 1.6), indicating that sacral neuromodulation is both safe and effective for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis: a prospective study. Comiter, CV.[2019]

In a study of 86 females with interstitial cystitis, a combination of intravesical electrostimulation and electromagnetophoresis with heparin significantly reduced pain, with 60% of participants reporting pain as 'rare'.

The treatment also halved the urgency to urinate and increased the mean effective bladder volume by 46.2%, indicating a substantial improvement in bladder function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Complex local and central therapy of interstitial cystitis with devices AMUS-01-INTRAMAG and AMO-ATOS-E]. Rokhlokov, IM., Raĭgorodskiĭ, IuM., Timoshenko, VO., et al.[2012]

Long-term transcutaneous electrical stimulation treatment can effectively help bring interstitial cystitis into remission, offering a conservative management option for patients.

The treatment appears to be more effective for the classic subtype of interstitial cystitis compared to the nonulcer subtype, suggesting that different subtypes may respond differently to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous electrical nerve stimulation in classic and nonulcer interstitial cystitis. Fall, M., Lindström, S.[2006]

Repetitive transcranial magnetic stimulation (rTMS) was found to be well tolerated in 11 patients with treatment-resistant chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), with no serious side effects reported and only mild headaches in a few cases.

The treatment showed moderate efficacy, with significant reductions in pain scores observed immediately after treatment and at follow-ups, suggesting rTMS could be a promising option for patients who do not respond to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Prospective Pilot Study. Nikkola, J., Holm, A., Seppänen, M., et al.[2020]

This study aims to evaluate the effects of transcranial direct current stimulation (tDCS) on pain, functionality, and mood in women with interstitial cystitis, using a randomized controlled trial design with two groups: active and sham stimulation.

If effective, tDCS could provide a safe, low-cost, and easy-to-use complementary treatment for interstitial cystitis, potentially leading to decreased pain and improved quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current electrical stimulation for the treatment of interstitial cystitis: A study protocol. Dutra, LRDV., Silva-Filho, E., Oliveira, MC., et al.[2021]

A 68-year-old woman with bladder pain syndrome experienced complete relief from suprapubic pain and a 60-80% reduction in micturition frequency after 16 sessions of high-intensity, low-frequency rTMS targeting the dorsolateral prefrontal cortex.

This study is the first to demonstrate that rTMS can effectively alleviate symptoms of bladder pain syndrome, improving not only pain and urinary symptoms but also overall quality of life and daily functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Relief of Painful Bladder Syndrome by High-Intensity, Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Right and Left Dorsolateral Prefrontal Cortices. Nizard, J., Esnault, J., Bouche, B., et al.[2020]

In a study involving multiple sclerosis (MS) patients with lower urinary tract symptoms, 5-Hz repetitive transcranial magnetic stimulation (rTMS) applied over the motor cortex for five consecutive days improved the voiding phase of urination.

The results suggest that increasing excitability in the corticospinal tract may help improve bladder function by enhancing detrusor contraction and urethral sphincter relaxation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of motor cortex rTMS on lower urinary tract dysfunction in multiple sclerosis. Centonze, D., Petta, F., Versace, V., et al.[2022]

In a study of 21 patients with chronic pelvic pain from interstitial cystitis, sacral neuromodulation (InterStim) significantly reduced pain levels and narcotic use, with a 36% decrease in mean morphine dose equivalents after implantation.

The majority of patients (20 out of 21) reported moderate to marked improvement in pain, and four patients were able to stop using narcotics altogether after the treatment, indicating the efficacy of this intervention for those with refractory symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacral neuromodulation decreases narcotic requirements in refractory interstitial cystitis. Peters, KM., Konstandt, D.[2022]

In a study of 34 female patients with interstitial cystitis, sacral neuromodulation significantly reduced pelvic pain and urgency/frequency symptoms over a mean follow-up of 86 months, indicating its long-term efficacy.

The treatment showed a substantial decrease in pain scores from an average of 6.5 to 2.4 on the visual analog pain scale, demonstrating that sacral neuromodulation can be a successful option for patients who have not responded to standard drug therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimum 6-year outcomes for interstitial cystitis treated with sacral neuromodulation. Marinkovic, SP., Gillen, LM., Marinkovic, CM.[2022]

References

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

Repetitive transcranial magnetic stimulation for chronic neuropathic pain in patients with bladder pain syndrome/interstitial cystitis. [2019]

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

Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis: a prospective study. [2019]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Complex local and central therapy of interstitial cystitis with devices AMUS-01-INTRAMAG and AMO-ATOS-E]. [2012]

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

Transcutaneous electrical nerve stimulation in classic and nonulcer interstitial cystitis. [2006]

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

Repetitive Transcranial Magnetic Stimulation for Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Prospective Pilot Study. [2020]

6. Ireland pubmed.ncbi.nlm.nih.gov

Transcranial direct current electrical stimulation for the treatment of interstitial cystitis: A study protocol. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Relief of Painful Bladder Syndrome by High-Intensity, Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Right and Left Dorsolateral Prefrontal Cortices. [2020]

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

Effects of motor cortex rTMS on lower urinary tract dysfunction in multiple sclerosis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Sacral neuromodulation decreases narcotic requirements in refractory interstitial cystitis. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Minimum 6-year outcomes for interstitial cystitis treated with sacral neuromodulation. [2022]