Clinical trial NCT03574610: Brain Targets in Patients With Bladder Emptying Difficulties
Official title: Supraspinal Mechanisms Involved in Voiding Dysfunction.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neurogenic Bladder
Multiple Sclerosis
Voiding Dysfunction
Keywords: Neurogenic bladder
Functional Neuroimaging
Transcranial Rotating Permanent Magnet Stimulator (TRPMS)
Lead sponsor: The Methodist Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2018-07-02
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this study is to identify brain centers specifically associated with "initiation of voiding" in patients with neurogenic bladder dysfunction. Currently there is no study that has evaluated brain centers involved in initiation of voiding in patients with neurogenic voiding dysfunction.

Patients with neurogenic bladder secondary to etiologies such as Multiple Sclerosis, Parkinson's disease, and Cerebrovascular accidents will be recruited in this study. Patients will be categorized into 2 groups, those who have trouble emptying their bladder and those who urinate appropriately. Our existing and unique functional magnetic resonance imaging (fMRI)/ urodynamics (UDS) platform is an ideal platform to identify brain regions involved in bladder emptying disorders as seen in patients with neurogenic bladder dysfunction and will be used for this study. After characterizing brain regions involved in bladder emptying, the investigator propose to use noninvasive transcutaneous magnetic stimulation in a subset of patients with voiding dysfunction in aim 3.

Detailed description: Difficulty in bladder emptying (Voiding dysfunction,VD) is a costly urinary condition that leads to urinary tract infections/stones, sepsis, bladder loss, and permanent kidney damage. VD can be present in patients with or without neurologic/brain disorders. Currently the only available therapies for VD include bladder catheters or intermittent self-catheterization. Catheterization is a burden especially in patients with nerve damage, hand skills may be limited. The cost and morbid side effects of catheterizations in patients (blood in the urine, pain, trauma, strictures, and infections) requires investigators to develop new therapies that are beyond the bladder. Such new therapies could target the brain (where bladder control is located).

In this proposal, investigators plan to further characterize the brain regions involved in bladder emptying for each patient and ,perform brain modulation, targeting these regions as a possible therapy for VD.

Patients with bladder dysfunction will be divided into two groups: Group 1: patients with VD; and Group 2: patients without VD. Specific Aim 1: To evaluate brain pattern in both groups and compare them to each other at the time of bladder emptying. Specific Aim 2: To evaluate reliability of the nerve fibers in the brain and see whether damage to these fibers is related to difficulty emptying the bladder. Specific Aim 3: To perform non-invasive brain stimulation on specific regions of the brain responsible for bladder control to improve bladder emptying.

This study is an interventional Study: The investigators have completed a well-powered study on twenty-seven female MS patients during their bladder storage phase. Aims 1 and 2 use the data from previously completed trial and investigators will perform additional imaging analysis on it. Aim 3 is a new and small trial in which investigators planned to modulate the regions of the brain that are related to bladder control.

Approximately 16 study participants will be enrolled at Houston Methodist, and 16 throughout the study.

Eligibility criteria: Inclusion Criteria:

Inclusion Criteria for subjects with neurogenic bladder:

* Patients with clinical diagnosis of neurogenic bladder
* History of any neurologic illness or injury (including but not limited to spinal cord injury, Multiple Sclerosis, Stroke, spina bifida, Parkinson's, major spine surgery)
* 18 years or older

Specifics for MS patients:

Adult female patients with clinically stable MS \[Expanded Disability Status Score (EDSS) ≤6.5\], with bladder symptoms ≥3 months, will be screened. Patients will be considered to have VD if they have an increased Postvoid Residual (≥ 20% Maximum Cystometric Capacity). Patients who perform self-catheterization will be included in the VD category as well.

Exclusion Criteria:

Exclusion Criteria for subjects with neurogenic bladder:

* Men (for aims 1 and 2 only), anatomical bladder outlet obstruction (anti-incontinence procedures, urethral strictures, or advanced pelvic organ prolapse). Severe debilitating MS, history of seizures, pregnancy or planning to become pregnant, contraindications to MRI, history of augmentation cystoplasty. Patients with active urinary tract infection (UTI) can be treated and subsequently screened for the trial.
* Positive urine pregnancy test at enrollment (There are no known risks to a subject's fetus. There is no known teratogenic risk associated with urodynamics or fMRI) - Cognitively impaired patients

Primary outcomes:
measure: Changes in Brain Activity After Treatment Measured Using Functional MRI
timeFrame: Baseline to three weeks
Secondary outcomes:
measure: Changes in Objective Clinical Outcomes Following Treatment
timeFrame: Baseline, after treatment and 4 month follow up
measure: Changes in %Post-Void Residual/Bladder Capacity (PVR/BC) Following Treatment
timeFrame: Baseline, after treatment and 4 month follow up
measure: Changes in Non-instrumented Uroflow Variable Qmax Following Treatment
timeFrame: Baseline, after treatment and 4 month follow up
measure: Changes in Liverpool Nomogram Following Treatment
timeFrame: Baseline, after treatment and 4 month follow-up
measure: Changes in Subjective Clinical Outcomes Following Treatment - Urinary Distress Inventory, Short Form (UDI-6) Questionnaire
timeFrame: Baseline, after treatment and 4 month follow up
measure: Changes in Subjective Clinical Outcomes Following Treatment - American Urological Association Symptom Score (AUASS) Questionnaire
timeFrame: Baseline, after treatment and 4 month follow up
measure: Changes in Subjective Clinical Outcomes Following Treatment - Neurogenic Bladder Symptom Score (NBSS) Questionnaire
timeFrame: Baseline, after treatment and 4 month follow up
Other outcomes:
Locations:
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
affiliation: The Methodist Hospital Research Institute
name: Rose Khavari, MD
role: PRINCIPAL_INVESTIGATOR
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citation: 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.
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