Non-Invasive Brain Stimulation for Neurogenic Bladder in MS

(MSBLADDER Trial)

Overseen By Betsy Salazar, PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: The Methodist Hospital Research Institute

Must not be taking: Antidepressants, Antipsychotics, Lithium, others

Disqualifiers: Pregnancy, Seizure disorder, Heart disease, 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: 14

Duration: 2 weeks

29 Participants Needed

Trial Summary

What is the purpose of this trial?

Neurogenic overactive bladder (NOAB), characterized by urinary frequency, urgency or urgency incontinence symptoms occurring during the storage phase of the bladder, is the most common urinary complaint in multiple sclerosis (MS). Current management options for NOAB in MS have limited efficacy and considerable adverse effects, which underscores the significance of this study and highlights the need for better, less invasive therapies. This novel study investigates brain therapeutic targets that could shift the focus of NOAB management in MS from a bladder-centric focus to brain restoration; specifically modulating the brain regions identified in the prior functional magnetic resonance imagining studies. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation that can modulate neurons (excite or inhibit) to improve the connectivity of the regions of interest (ROI). The preliminary data demonstrate, for the first time, significant improvement in bladder symptoms in ten women with MS who have voiding dysfunction following multifocal transcranial magnetic stimulation without any treatment-related adverse effects. This randomized double-blind, sham-controlled single center clinical trial with an optional open-label extension (OLE) phase is designed to evaluate the effects of targeted rTMS in women with MS and NOAB by investigating restorative reorganization of brain function The main purpose of this study is to determine the effects of individualized repetitive Transcranial Magnetic Stimulation (rTMS) for improving overactive bladder symptoms such as urinary frequency and urgency with or without incontinence in individuals with multiple sclerosis (MS). Patients will undergo initial screening that includes a demographics information, physical exam, past medical and surgical history, medication list, urine pregnancy test (female subjects with childbearing potential), and completion of questionnaires to confirm the eligibility of patients. All eligible patients will be required to complete a functional MRI scan followed by locating the regions of interest through neural navigation system and finally receiving 10 treatment sessions. Since this is a randomized trial, some patients will receive active treatment/ therapy sessions while others will only receive sham or placebo treatments. The total duration to complete all treatment sessions and follow up visits is approximately 4-5 months.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking medications that lower the seizure threshold or exacerbate bipolar disorder, you may be excluded from participating.

What data supports the effectiveness of the treatment Magstim Rapid2 System, Repetitive Transcranial Magnetic Stimulation (rTMS) for neurogenic bladder in MS?

Research shows that repetitive transcranial magnetic stimulation (rTMS) over the motor cortex can improve bladder function in multiple sclerosis (MS) patients by enhancing the ability to urinate. This suggests that rTMS might help with bladder issues in MS by improving muscle control involved in urination. ^{1 2 3 4 5}

Is non-invasive brain stimulation safe for humans?

Non-invasive brain stimulation, like repetitive Transcranial Magnetic Stimulation (rTMS), has been studied for various conditions and is generally considered safe in humans. Studies have shown it can be used without serious side effects for conditions like neuropathic pain, voiding dysfunction in multiple sclerosis, and urinary disturbances in Parkinson's disease. ^{2 3 4 5 6}

How is the Magstim Rapid2 System treatment different from other treatments for neurogenic bladder in MS?

The Magstim Rapid2 System, using repetitive Transcranial Magnetic Stimulation (rTMS), is unique because it is a non-invasive treatment that targets the brain to improve bladder function, unlike traditional methods like catheterization which directly manage the bladder. This approach aims to enhance brain and spinal cord communication to improve bladder control in MS patients. ^{1 2 3 4 5}

Research Team

Rose Khavari, MD

Principal Investigator

The Methodist Hospital Research Institute

Eligibility Criteria

This trial is for adult women with Multiple Sclerosis (MS) who have stable MS symptoms and experience overactive bladder issues. They must not be pregnant, planning to become pregnant, or nursing, and should not have a history of certain mental health conditions or be on medications that could worsen these conditions.

Inclusion Criteria

You need to score higher than 10 on the Montreal Cognitive Assessment (MoCA) test to be eligible.

I experience frequent urination, urgency, or need to urinate at night.

I am a woman aged 18 or older.

Exclusion Criteria

You have a history of autonomic dysreflexia.

Tests show that your bladder has trouble emptying.

You have a baclofen pump or any other pump implanted in your body, or a pacemaker.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 10 sessions of repetitive transcranial magnetic stimulation (rTMS) over two weeks

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

3 visits (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Magstim Rapid2 System

Trial Overview The study tests the effects of repetitive Transcranial Magnetic Stimulation (rTMS), a noninvasive brain therapy aimed at improving bladder control in women with MS. Participants will undergo treatment sessions after an initial screening and functional MRI scan to locate target brain regions.

Participant Groups

Group I: Active rTMS Active Control 1 Intervention

1 Hz (LF) and 10 Hz (HF) rTMS stimulation will be delivered at 90% of the resting motor threshold for 40 min each week day for two weeks.

Group II: Sham rTMS Placebo Group 1 Intervention

Low-frequency (1Hz) active rTMS stimulation will be delivered with an inert "sham" stimulation coil for 40 min each week day for two weeks.

Magstim Rapid2 System is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Magstim Rapid2 System for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraine with aura

Approved in European Union as Magstim Rapid2 System for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Approved in Canada as Magstim Rapid2 System for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Findings from Research

Transcutaneous magnetic spinal cord stimulation (TMSCS) significantly improved bladder function in five individuals with chronic spinal cord injury, enabling all subjects to achieve voluntary urination after treatment.

After 16 weeks of TMSCS, participants experienced a notable increase in urine volume produced voluntarily (from 0 cc/day to 1120 cc/day) and a decrease in self-catheterization frequency, indicating enhanced bladder capacity and improved quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Proof-of-Concept Study of Transcutaneous Magnetic Spinal Cord Stimulation for Neurogenic Bladder. Niu, T., Bennett, CJ., Keller, TL., et al.[2022]

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 pilot trial involving 10 women with multiple sclerosis and voiding dysfunction, the Transcranial Rotating Permanent Magnet Stimulator (TRPMS) was found to be safe, with no reported adverse effects during treatment.

Post-treatment results showed significant improvements in brain activation related to voiding initiation and a decrease in post-void residual bladder capacity, indicating that TRPMS can effectively enhance bladder emptying in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive, Individualized Cortical Modulation Using Transcranial Rotating Permanent Magnet Stimulator for Voiding Dysfunction in Women with Multiple Sclerosis: A Pilot Trial. Khavari, R., Tran, K., Helekar, SA., et al.[2022]

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]

This pilot clinical trial aims to explore the feasibility of using Transcranial Rotating Permanent Magnet Stimulator (TRPMS) to treat voiding dysfunction in 10 female MS patients, marking a novel approach by targeting brain regions involved in bladder control.

If successful, this non-invasive method could provide a new therapeutic option for managing urinary dysfunction in MS patients, potentially leading to better understanding and treatment of neurogenic lower urinary tract dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effects of non-invasive, individualized, transcranial neuromodulation treatment for voiding dysfunction in multiple sclerosis patients: study protocol for a pilot clinical trial. Tran, K., Shi, Z., Karmonik, C., et al.[2022]

A 2-week course of low frequency 1 Hz repetitive transcranial magnetic stimulation (rTMS) improved urinary tract function in 8 advanced Parkinson's disease patients, increasing bladder capacity and the sensation of filling.

Patients reported a significant reduction in urinary symptoms, as measured by the International Prostate Symptoms Score (IPSS), with benefits lasting up to 2 weeks after treatment, suggesting rTMS is a promising noninvasive option for managing urinary disturbances in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of inhibitory rTMS on bladder function in Parkinson's disease patients. Brusa, L., Finazzi Agrò, E., Petta, F., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A Proof-of-Concept Study of Transcutaneous Magnetic Spinal Cord Stimulation for Neurogenic Bladder. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Noninvasive, Individualized Cortical Modulation Using Transcranial Rotating Permanent Magnet Stimulator for Voiding Dysfunction in Women with Multiple Sclerosis: A Pilot Trial. [2022]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Therapeutic effects of non-invasive, individualized, transcranial neuromodulation treatment for voiding dysfunction in multiple sclerosis patients: study protocol for a pilot clinical trial. [2022]

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

Effects of inhibitory rTMS on bladder function in Parkinson's disease patients. [2022]