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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat overactive bladder symptoms in women with multiple sclerosis (MS) using repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique. Researchers are shifting focus from bladder treatments to targeting brain regions that affect bladder function, aiming to reduce symptoms like frequent and urgent urination. Women with MS who have experienced bladder issues for at least three months may be suitable for this study. Participants will receive either real or sham (placebo) treatments over several months to determine if this approach can improve symptoms. As an unphased trial, this study offers participants the chance to contribute to pioneering research that could lead to new treatment options.

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 prior data suggests that this non-invasive brain stimulation is safe for treating neurogenic bladder in MS?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe for people with multiple sclerosis (MS). One study found that patients with MS tolerated rTMS well, with no serious side effects. In a small study of ten women with MS, participants demonstrated significant improvement in bladder symptoms after rTMS treatment, and no treatment-related adverse effects were reported. This suggests that rTMS is both effective and safe for managing symptoms of an overactive bladder caused by nerve issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of non-invasive brain stimulation for neurogenic bladder in MS patients because it represents a novel approach to treatment. Traditional options often involve medications or invasive procedures, but this method uses repetitive transcranial magnetic stimulation (rTMS) to potentially improve bladder control. The Magstim Rapid2 System delivers targeted magnetic pulses to specific brain areas, which could enhance neural pathways involved in bladder function. This non-invasive technique might offer a safer alternative with fewer side effects compared to existing treatments, making it a promising development for individuals with this condition.

What evidence suggests that this non-invasive brain stimulation is effective for neurogenic bladder in MS?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) may help people with multiple sclerosis (MS) who have bladder problems. In a previous study, ten women with MS experienced significant improvement in their bladder symptoms after receiving rTMS treatment. This trial will compare two different approaches: participants will receive either active rTMS using the Magstim Rapid2 System or a sham rTMS treatment. The method uses magnetic pulses to stimulate certain brain areas, potentially improving their coordination. Importantly, these improvements occurred without any side effects from the treatment. While research is ongoing, these early results suggest that rTMS could be a promising option for managing bladder issues in people with MS. ^{1 2 3 6 7}

Who Is on the Research Team?

Rose Khavari, MD

Principal Investigator

The Methodist Hospital Research Institute

Are You a Good Fit for This Trial?

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 had a UTI, but it's treated and my latest urine test was clear.

Exclusion Criteria

You have a history of autonomic dysreflexia.

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

Tests show that your bladder has trouble emptying.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06072703

Study Details | NCT06072703 | Neuromodulating Cortical ... The Magstim Rapid2 system is indicated to be used in Multiple Sclerosis patients as target users with lower urinary tract symptoms such as urinary frequency, ...

2. withpower.com withpower.com/trial/phase-multiple-sclerosis-2-2023-8348a

Non-Invasive Brain Stimulation for Neurogenic Bladder in MS The preliminary data demonstrate, for the first time, significant improvement in bladder symptoms in ten women with MS who have voiding dysfunction following ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10809615/

Evaluating noninvasive brain stimulation to treat overactive ... We leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39245707/

A phase II trial examining the safety and preliminary ... This study will determine if rTMS can improve functional outcomes or other MS symptoms and determine whether rTMS has the potential to promote remyelination in ...

5. nationalmssociety.org nationalmssociety.org/how-you-can-help/get-involved/participate-in-research-studies/participate-in-clinical-trials/clinical-trial-brain-stim-overactive-bladder

Clinical Trial: Brain Stimulation for Overactive Bladder A non-invasive brain stimulation technique called repetitive transcranial magnetic stimulation (rTMS) in ten women with MS who have NOAB, we found it improved ...

6. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08425-x

A phase II trial examining the safety and preliminary efficacy of ... This study will determine if rTMS can improve functional outcomes or other MS symptoms and determine whether rTMS has the potential to promote remyelination in ...

7. researchgate.net researchgate.net/publication/380626903_Low-intensity_repetitive_transcranial_magnetic_stimulation_is_safe_and_well_tolerated_by_people_living_with_MS_-_outcomes_of_the_phase_I_randomised_controlled_trial_TAURUS

Low-intensity repetitive transcranial magnetic stimulation is ... Low-intensity repetitive transcranial magnetic stimulation is safe and well tolerated by people living with MS – outcomes of the phase I randomised controlled ...