Neuromodulating Cortical Regions Involved in Neurogenic Bladder in MS

NCT06072703 | Recruiting DMC FDA Device

• 1 other identifier: PRO00035884
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neurogenic Bladder; Multiple Sclerosis; Overactive Bladder

Keywords

Neurogenic bladder; Functional Neuroimaging; repetitive Transcranial Magnetic Stimulation (rTMS); Neuromodulation

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline, 1 week after, 1 month after and 3 months after rTMS treatment

• 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.

  Baseline, 1 week after, 1 month after and 3 months after rTMS treatment

Secondary Outcomes (3)

• Changes in brain activation patterns following rTMS treatment - functional MRI imaging

  Baseline and 1 week after rTMS treatment

• Changes in objective clinical outcomes following treatment - Bladder Capacity

  Baseline, 1 week after, 1 month after and 3 months after rTMS treatment

• Changes in %Post-Void Residual/Bladder Capacity (PVR/BC) following treatment

  Baseline, 1 week after, 1 month after and 3 months after rTMS treatment

Other Outcomes (3)

• Changes in subjective clinical outcomes following treatment - American Urological Association Symptom Score (AUASS) Questionnaire

  Baseline, 1 week after, 1 month after and 3 months after rTMS treatment

• Changes in subjective clinical outcomes following treatment - Incontinence Impact Questionnaire Short Form (IIQ-7)

  Baseline, 1 week after, 1 month after and 3 months after rTMS treatment

• Changes in subjective clinical outcomes following treatment - Overactive Bladder (OAB) Awareness Tool

  Baseline, 1 week after, 1 month after and 3 months after rTMS treatment

Study Arms (2)

Active rTMS

ACTIVE COMPARATOR

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.

Device: Magstim Rapid2 System

Sham rTMS

SHAM COMPARATOR

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

Device: Magstim Rapid2 System

Interventions

Magstim Rapid2 System DEVICE

The 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.

Also known as: Repetitive Transcranial Magnetic Stimulation

Active rTMS; Sham rTMS

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• At least one bladder storage symptoms (e.g., urinary frequency, urinary urgency, nocturia with or without incontinence) indicated by OAB -AT≥ 8
• Individuals with active urinary tract infection (UTI) will be treated and will be enrolled after negative urinalysis

You may not qualify if:

• 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.
• History of bipolar disorder, or individuals who are taking medications that can exacerbate the condition such as tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-nor-epinephrine reuptake inhibitors, anti-psychotics, lithium, bupropion (Wellbutrin) and antihistamines will be excluded.
• All intracranial lesions and hemorrhagic stroke will be excluded
• History of moderate to severe heart disease or unstable angina
• History of Autonomic Dysreflexia
• History of interstitial cystitis, pelvic radiation
• Intra-detrusor botulinumtoxinA (BTX-A) injection over the past 6 months
• Incarcerated patients will be excluded.
• Active sacral nerve stimulation (SNS) device or any other spinal stimulators
• Indwelling urethral or suprapubic catheter

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Related Publications (8)

• Khavari R, Elias SN, Boone T, Karmonik C. Similarity of functional connectivity patterns in patients with multiple sclerosis who void spontaneously versus patients with voiding dysfunction. Neurourol Urodyn. 2019 Jan;38(1):239-247. doi: 10.1002/nau.23837. Epub 2018 Oct 12.

  PMID: 30311665 BACKGROUND

• Khavari R, Elias SN, Pande R, Wu KM, Boone TB, Karmonik C. Higher Neural Correlates in Patients with Multiple Sclerosis and Neurogenic Overactive Bladder Following Treatment with Intradetrusor Injection of OnabotulinumtoxinA. J Urol. 2019 Jan;201(1):135-140. doi: 10.1016/j.juro.2018.07.066.

  PMID: 30076906 BACKGROUND

• Khavari R, Tran K, Helekar SA, Shi Z, Karmonik C, Rajab H, John B, Jalali A, Boone T. Noninvasive, Individualized Cortical Modulation Using Transcranial Rotating Permanent Magnet Stimulator for Voiding Dysfunction in Women with Multiple Sclerosis: A Pilot Trial. J Urol. 2022 Mar;207(3):657-668. doi: 10.1097/JU.0000000000002297. Epub 2021 Oct 25.

  PMID: 34694911 BACKGROUND

• Khavari R, Karmonik C, Shy M, Fletcher S, Boone T. Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis. J Urol. 2017 Feb;197(2):438-444. doi: 10.1016/j.juro.2016.09.077. Epub 2016 Sep 21.

  PMID: 27664581 BACKGROUND

• Shi Z, Tran K, Karmonik C, Boone T, Khavari R. High spatial correlation in brain connectivity between micturition and resting states within bladder-related networks using 7 T MRI in multiple sclerosis women with voiding dysfunction. World J Urol. 2021 Sep;39(9):3525-3531. doi: 10.1007/s00345-021-03599-4. Epub 2021 Jan 29.

  PMID: 33512570 BACKGROUND

• Tran K, Karmonik C, Boone TB, Khavari R. Are White Matter Tract Integrities Different in Multiple Sclerosis Women With Voiding Dysfunction? Female Pelvic Med Reconstr Surg. 2021 Jan 1;27(1):e101-e105. doi: 10.1097/SPV.0000000000000830.

  PMID: 32265400 BACKGROUND

• Tran K, Shi Z, Karmonik C, John B, Rajab H, Helekar SA, Boone T, Khavari R. Therapeutic effects of non-invasive, individualized, transcranial neuromodulation treatment for voiding dysfunction in multiple sclerosis patients: study protocol for a pilot clinical trial. Pilot Feasibility Stud. 2021 Mar 24;7(1):83. doi: 10.1186/s40814-021-00825-z.

  PMID: 33757581 BACKGROUND

• Salazar BH, Hoffman KA, Lincoln JA, Karmonik C, Rajab H, Helekar SA, Khavari R. Evaluating noninvasive brain stimulation to treat overactive bladder in individuals with multiple sclerosis: a randomized controlled trial protocol. BMC Urol. 2024 Jan 25;24(1):20. doi: 10.1186/s12894-023-01358-8.

  PMID: 38273296 DERIVED

MeSH Terms

Conditions

Urinary Bladder, Neurogenic; Multiple Sclerosis; Urinary Bladder, Overactive

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Lower Urinary Tract Symptoms; Urological Manifestations

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Rose Khavari, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rose Khavari, MD

CONTACT

7137030660; rkhavari@houstonmethodist.org

Betsy Salazar, PhD

CONTACT

bhsalazar@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking: Double (participants and principal investigator and co-investigator)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD/PI

Model Details: Intervention Model: 2:1 active: sham assignment, with an optional OLE phase

Study Record Dates

• First Submitted: May 11, 2023
• First Posted: October 10, 2023
• Study Start: October 30, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

US (1)