Neuromodulating Cortical Regions Involved in Neurogenic Bladder in MS
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age18+
SponsorThe Methodist Hospital Research Institute
About 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adult women (≥ 18 years of age)
Clinically stable MS defined as ExpandedDisability Status Score (EDSS) ≤ 7.5without exacerbation worsening in the preceding 6 months prior to study entry
Neurogenic Lower Urinary Tract Dysfunction symptoms ≥ 3 months with NBSS total ≥ 15
Individuals with Montreal Cognitive Assessment (MoCA) score >10 will be eligible
Disqualifiers
Pregnant/planning to become pregnant or nursing
Urodynamic findings of bladder outlet obstruction
Baclofen or other intrathecal pumps, Pacemakers.
History of seizure disorder (SZ), immediate family of SZ disorder, in addition to individuals who are taking any medications such as (bupropion) Wellbutrin or substances (ex: heavy alcohol use) that would lower seizure threshold will be excluded.
Trial design
Design model
Parallel
Treatments tested in this trial
Magstim Rapid2 System
DeviceThe Magstim Rapid2 system is the most commonly used magnetic stimulation system for rTMS clinical studies and therapeutic investigations, capable of selectively inducing, modulating or suppressing neuronal activity. This rTMS device will be used along with the D70 Alpha Coil package, which includes an active coil ideal for focal rTMS and a sham coil, The placebo coil looks identical to its active version and replicates pulse noise without producing the magnetic field necessary to modulate cortical neurons. Additionally, the investigators will be utilizing the StimGuide navigation system (currently available at the HMRI) to accurately target the proposed regions of interest. 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, urinary urgency, urinary incontinence and voiding dysfunction.
Treatment groups
29 Participants
are divided into 2 treatment groupsGroup A: Active rTMSActive comparator 1 intervention
Group B: Sham rTMSSham comparator 1 intervention
Trial outcomes
Primary outcomes
1
Changes in subjective clinical outcomes following treatment - Neurogenic Bladder Symptom Score (NBSS) Questionnaire
The subjective clinical assessment includes changes in validated questionnaires. This assessment has 24 questions that measure bladder symptoms across 3 different domains: incontinence (score range: 0-29), storage and voiding (score range: 0-22), and consequences (score range: 0-23); the highest score is associated with worse symptoms. The last question focuses on quality of life scored from 0 (pleased) to 4 (unhappy). The investigators report raw scores here for all domains and QoL.
Time frame
Baseline, 1 week after, 1 month after and 3 months after rTMS treatment2
Changes on patient reported outcomes following treatment - 2 day bladder diary
Here the investigators evaluate changes on the number of times that symptoms associated with neurogenic overactive bladder occur in a 24hr period after rTMS treatment. Reported outcomes by patients include the number of times the following occur: voids, nocturia, severe urgency episodes, and urgency urinary incontinence episodes.
Time frame
Baseline, 1 week after, 1 month after and 3 months after rTMS treatmentSecondary outcomes
1
Changes in brain activation patterns following rTMS treatment - functional MRI imaging
Effect of rTMS treatment in increasing/decreasing activation in ROIs known to be involved in bladder function measured by changes in blood-oxygen-level-dependent (BOLD) signal.
Time frame
Baseline and 1 week after rTMS treatment2
Changes in objective clinical outcomes following treatment - Bladder Capacity
The objective clinical assessment includes changes in bladder capacity (mL), which is assessed by collecting both post void residual (PVR) and voided volume (both in mL) in participants after treatment as compared to baseline.
Time frame
Baseline, 1 week after, 1 month after and 3 months after rTMS treatment3
Changes in %Post-Void Residual/Bladder Capacity (PVR/BC) following treatment
Percentage of PVR in proportion to the bladder capacity will be measured before the intervention and post intervention at 1 and 3 months follow up and will be compared between active and sham neurostimulation groups
Time frame
Baseline, 1 week after, 1 month after and 3 months after rTMS treatmentOther outcomes
1
Changes in subjective clinical outcomes following treatment - American Urological Association Symptom Score (AUASS) Questionnaire
The subjective clinical assessment includes changes in validated questionnaires. This assessment has 8 questions and is used to assess how bothersome urinary symptoms are and quality of life. The investigators report raw scores here for questions pertaining to voiding symptoms. Questions 1-7 have the following score range: 0-5 (with the highest score associated with worse symptoms). The last question pertains to quality of life and has a score range of: 0-6 (with the highest score associated with very reduced quality of life).
Time frame
Baseline, 1 week after, 1 month after and 3 months after rTMS treatment2
Changes in subjective clinical outcomes following treatment - Incontinence Impact Questionnaire Short Form (IIQ-7)
The subjective clinical assessment includes changes in validated questionnaires. This assessment has 7 questions and is used to assess the impact urine leakage has on a patient's activities, relationships, and feelings. Each question has the following score range: 0-3 (with the highest score associated with higher symptom distress).
Time frame
Baseline, 1 week after, 1 month after and 3 months after rTMS treatment3
Changes in subjective clinical outcomes following treatment - Overactive Bladder (OAB) Awareness Tool
The subjective clinical assessment includes changes in validated questionnaires. The OAB Awareness Tool assessment has 9 questions. It allows participants to score symptoms and illustrates how these symptoms may be affecting quality of life. Questions 1-8 have a score range of 0-5 (the higher the score the more bothersome the symptom is) and the last questions asks if the participant is male (if so 2 points are added to the total score).
Time frame
Baseline, 1 week after, 1 month after and 3 months after rTMS treatmentSponsors and contacts
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Source ClinicalTrials.gov