Repetitive Transcranial Magnetic Stimulation in Women With Overactive Bladder With Urgency Incontinence

Study Overview
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Brief Summary
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Overactive bladder (OAB) affects an estimated 16-30% of women in the US and urgency urinary incontinence (UUI) affects 7-11% of women with OAB. It is known that repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) can modulate the pelvic floor muscle activity with potential benefits for various urologic conditions. The goal of this study is to assess feasibility of rTMS as a treatment option for OAB with UUI by determining which rTMS frequency is most effective in targeting sensory components of OAB, namely urinary urgency, and also in targeting the brain network known to be involved in OAB.

Detailed Description
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Eligible participants with OAB and UUI will undergo resting state functional MRI of the brain to map baseline brain activity. Participants will then undergo rTMS of the SMA with electromyography (EMG) monitoring of the pelvic floor muscles. They will then undergo another MRI to assess and changes in brain activity due to rTMS. Participants will be asked about their bladder symptoms over the course of the study. The study will have a crossover design. The investigators plan to recruit 10 women with symptoms of OAB and UUI. During the first week, participants will be screened, asked to fill out a bladder questionnaire, and to complete a bladder diary. During the next two weeks, participants will undergo rTMS and functional MRI of the brain to assess brain activity. All participants will undergo two different known rTMS protocols for the pelvic floor, high-frequency and low-frequency, separated by a 1-week washout period. Each participant will be randomized to which protocol they will have first. In total, 5 participants will have started with high-frequency rTMS first and 5 participants will have started with low-frequency rTMS. At the end, all participants will have undergone both high- and low-frequency rTMS. The primary objective of the study is to assess the feasibility of rTMS in patients with OAB and UUI, which will be assessed with recruitment and retention rates of participants. The investigators also aim to determine if SMA activity mediates OAB symptoms and pelvic floor muscle tone using functional MRI of the brain. Finally, the investigators want to assess bladder symptoms following rTMS using participant questionnaires and number of UUI episodes.

Official Title
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Motor Cortical Neuromodulation With Repetitive Transcranial Magnetic Stimulation in Women With Overactive Bladder and Urgency Urinary Incontinence

Conditions
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Overactive Bladder, Urge Incontinence

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older female diagnosis of overactive bladder with symptoms of urgency urinary incontinence majority of the time during the last 3 months Exclusion Criteria: current use of sacral neuromodulation new initiation of overactive bladder treatment within the last 6 weeks has had intradetrusor onabotulinumtoxinA injections in the last 3 months neurological disease affecting the bladder or bowel incomplete bladder emptying history of urologic cancer active infection history of cystitis caused by tuberculosis, radiation, or chemotherapies severe pelvic pain pregnancy post-partum 6 weeks post-surgical 6 weeks cannot undergo MRI history of epilepsy or seizures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Two different intervention protocols will be administered in a crossover design.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Frequency rTMS Protocol<br>High frequency with 10 Hz at 80% motor threshold intensity with figure-of-eight coil for a total of 2,000 pulses. Pulses will be delivered in 10-second trains with a 50-second pause between the trains. | Device: Repetitive Transcranial Magnetic Stimulation<br>* rTMS uses pulses of magnetic energy to non-invasively stimulate the brain. The rTMS device to be used in this study is the Magstim Rapid2 Plus1. The rTMS device is connected to an active figure-of-eight coil which rests against the scalp and delivers the magnetic energy to the brain. The rTMS protocol is specified by the parameters of pulse frequency, duration of continuous pulse delivery, intensity, and stimulation location. Each participant will receive two different standard rTMS protocols that have been used in past research studies for modulation of pelvic floor tone delivered over the motor cortex in an area that is known to control pelvic floor muscles.<br>|
| Experimental: Low Frequency rTMS Protocol<br>Low frequency 1 Hz at 80% motor threshold intensity with figure-of-eight coil for a total of 2,000 pulses. Pulses will be delivered continuously. | Device: Repetitive Transcranial Magnetic Stimulation<br>* rTMS uses pulses of magnetic energy to non-invasively stimulate the brain. The rTMS device to be used in this study is the Magstim Rapid2 Plus1. The rTMS device is connected to an active figure-of-eight coil which rests against the scalp and delivers the magnetic energy to the brain. The rTMS protocol is specified by the parameters of pulse frequency, duration of continuous pulse delivery, intensity, and stimulation location. Each participant will receive two different standard rTMS protocols that have been used in past research studies for modulation of pelvic floor tone delivered over the motor cortex in an area that is known to control pelvic floor muscles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of repetitive transcranial magnetic stimulation (rTMS) on pelvic-supplementary motor area (SMA) activity after low-frequency rTMS | The effects of low-frequency rTMS on brain activity will be evaluated with functional MRI performed immediately before the rTMS session and also after 30 minutes after the session in order to document interval changes. | Functional MRI lasting 30 minutes will be obtained immediately before low-frequency rTMS during weeks 2 and 3. | 
| Effects of repetitive transcranial magnetic stimulation (rTMS) on pelvic-supplementary motor area (SMA) activity after low-frequency rTMS | The effects of low-frequency rTMS on brain activity will be evaluated with functional MRI performed immediately before the rTMS session and also after 30 minutes after the session in order to document interval changes. | Functional MRI lasting 30 minutes will be obtained within 30 minutes of finishing low-frequency rTMS during weeks 2 and 3. | 
| Effects of rTMS on pelvic-SMA activity after high-frequency rTMS | The effects of high-frequency rTMS on brain activity will be evaluated with functional MRI performed immediately before the rTMS session and also after 30 minutes after the session in order to document interval changes. | Functional MRI lasting 30 minutes will be obtained immediately before high-frequency rTMS during weeks 2 and 3. | 
| Effects of rTMS on pelvic-SMA activity after high-frequency rTMS | The effects of high-frequency rTMS on brain activity will be evaluated with functional MRI performed immediately before the rTMS session and also after 30 minutes after the session in order to document interval changes. | Functional MRI lasting 30 minutes will be obtained within 30 minutes of finishing high-frequency rTMS during weeks 2 and 3. | 
| Effects of rTMS on pelvic floor muscle activity after low-frequency rTMS | The effects of low-frequency rTMS on pelvic floor muscle activity will be evaluated with pelvic floor electromyography (EMG) obtained with a rectal sensor during the low-frequency rTMS session. | Pelvic floor EMG will be obtained during low-frequency rTMS session, lasting 33 minutes, during weeks 2 and 3. | 
| Effects of rTMS on pelvic floor muscle activity after high-frequency rTMS | The effects of high-frequency rTMS on pelvic floor muscle activity will be evaluated with pelvic floor electromyography (EMG) obtained with a rectal sensor during the high-frequency rTMS session. | Pelvic floor EMG will be obtained during high-frequency rTMS session, lasting 20 minutes, during weeks 2 and 3. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess subjective OAB and UUI symptom changes following rTMS | OAB and UUI symptoms will be assessed with the overactive bladder questionnaire (OAB-q). This validated instrument contains 33 questions regarding bladder symptoms and quality of life associated with OAB rated on a 6-point Likert scale. The total score ranges from 0 to 100 with higher scores reflecting greater degree of symptom bother. | Subjective OAB and UUI symptoms will be assessed with the OAB-q at baseline during week 1. | 
| Assess subjective OAB and UUI symptom changes following rTMS | OAB and UUI symptoms will be assessed with the overactive bladder questionnaire (OAB-q). This validated instrument contains 33 questions regarding bladder symptoms and quality of life associated with OAB rated on a 6-point Likert scale. The total score ranges from 0 to 100 with higher scores reflecting greater degree of symptom bother. | Subjective OAB and UUI symptoms will be assessed with the OAB-q after rTMS treatments during weeks 2 and 3. | 
| Assess objective OAB and UUI symptom changes following rTMS | Objective OAB and UUI symptoms will be assessed with a bladder diary where participants will document number of voids, volume of voids, urgency episodes, and episodes of urgency incontinence in the past 24 hours. | Objective OAB and UUI symptoms will be assessed with a bladder diary at baseline during week 1. | 
| Assess objective OAB and UUI symptom changes following rTMS | Objective OAB and UUI symptoms will be assessed with a bladder diary where participants will document number of voids, urgency episodes, and episodes of urgency incontinence in the past 24 hours. | Objective OAB and UUI symptoms will be assessed with a bladder diary after rTMS treatments during weeks 2 and 3. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Repetitive Transcranial Magnetic Stimulation, Overactive Bladder, Urge Incontinence