Brain Targets in Patients With Bladder Emptying Difficulties

NCT03574610 | Completed Results FDA Device

• 3 other identifiers: Pro00019329K12DK083014K23DK118209
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Neurogenic Bladder; Multiple Sclerosis; Voiding Dysfunction

Keywords

Neurogenic bladder; Functional Neuroimaging; Transcranial Rotating Permanent Magnet Stimulator (TRPMS)

Outcome Measures

Primary Outcomes (1)

• Changes in Brain Activity After Treatment Measured Using Functional MRI

  Here we measured changes in brain activation in modulated brain regions of interest (ROI) via blood oxygen level-dependent (BOLD) signals during "strong desire to void" and "voiding initiation (attempt)". We determined if there was a significant increase or decrease in activity (voxel signal) after treatment using the following criteria: 1) increase in activation was defined as T-value greater than 2.074 and 2) decrease in activation was defined as T-value less than 2.074.

  Baseline to three weeks

Secondary Outcomes (7)

• Changes in Objective Clinical Outcomes Following Treatment

  Baseline, after treatment and 4 month follow up

• Changes in %Post-Void Residual/Bladder Capacity (PVR/BC) Following Treatment

  Baseline, after treatment and 4 month follow up

• Changes in Non-instrumented Uroflow Variable Qmax Following Treatment

  Baseline, after treatment and 4 month follow up

• Changes in Liverpool Nomogram Following Treatment

  Baseline, after treatment and 4 month follow-up

• Changes in Subjective Clinical Outcomes Following Treatment - Urinary Distress Inventory, Short Form (UDI-6) Questionnaire

  Baseline, after treatment and 4 month follow up

Study Arms (1)

Subjects with Multiple Sclerosis and Voiding Dysfunction

EXPERIMENTAL

Subjects with Multiple Sclerosis (MS) and voiding dysfunction (VD). In this group 'Transcranial Rotating Permanent Magnet Stimulator (TRPMS)' device will be used.

Device: Transcranial Rotating Permanent Magnet Stimulator (TRPMS)

Interventions

Transcranial Rotating Permanent Magnet Stimulator (TRPMS) DEVICE

TRPMS is a wearable non-invasive transcranial rotating permanent magnet stimulator. It has been determined to be a Non Significant Risk device by the FDA. The amount and frequency of therapy are prescribed by the physician, and the device is custom configured to the patient to deliver the required amount of treatment. The device does not turn on until it is time for the treatment. It consists of three main parts: Neoprene cap with microstimulator(s), stimulator console (device controller box) and the tablet with TRPMS app which activates the console. The neoprene cap prevents the microstimulator(s) from coming in direct contact with the scalp. Microstimulators deliver the magnetic stimulation to the brain based on a prescription program uploaded in the stimulator controller.

Subjects with Multiple Sclerosis and Voiding Dysfunction

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Related Publications (14)

• Panicker JN, Fowler CJ, Kessler TM. Lower urinary tract dysfunction in the neurological patient: clinical assessment and management. Lancet Neurol. 2015 Jul;14(7):720-32. doi: 10.1016/S1474-4422(15)00070-8.

  PMID: 26067125 BACKGROUND

• Kuhtz-Buschbeck JP, Gilster R, van der Horst C, Hamann M, Wolff S, Jansen O. Control of bladder sensations: an fMRI study of brain activity and effective connectivity. Neuroimage. 2009 Aug 1;47(1):18-27. doi: 10.1016/j.neuroimage.2009.04.020. Epub 2009 Apr 14.

  PMID: 19371782 BACKGROUND

• Shy M, Fung S, Boone TB, Karmonik C, Fletcher SG, Khavari R. Functional magnetic resonance imaging during urodynamic testing identifies brain structures initiating micturition. J Urol. 2014 Oct;192(4):1149-54. doi: 10.1016/j.juro.2014.04.090. Epub 2014 Apr 21.

  PMID: 24769029 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

• Kuhtz-Buschbeck JP, van der Horst C, Wolff S, Filippow N, Nabavi A, Jansen O, Braun PM. Activation of the supplementary motor area (SMA) during voluntary pelvic floor muscle contractions--an fMRI study. Neuroimage. 2007 Apr 1;35(2):449-57. doi: 10.1016/j.neuroimage.2006.12.032. Epub 2007 Jan 9.

  PMID: 17293127 BACKGROUND

• Kuhtz-Buschbeck JP, van der Horst C, Pott C, Wolff S, Nabavi A, Jansen O, Junemann KP. Cortical representation of the urge to void: a functional magnetic resonance imaging study. J Urol. 2005 Oct;174(4 Pt 1):1477-81. doi: 10.1097/01.ju.0000173007.84102.7c.

  PMID: 16145475 BACKGROUND

• Blok BF, Sturms LM, Holstege G. Brain activation during micturition in women. Brain. 1998 Nov;121 ( Pt 11):2033-42. doi: 10.1093/brain/121.11.2033.

  PMID: 9827764 BACKGROUND

• Blok BF, Willemsen AT, Holstege G. A PET study on brain control of micturition in humans. Brain. 1997 Jan;120 ( Pt 1):111-21. doi: 10.1093/brain/120.1.111.

  PMID: 9055802 BACKGROUND

• Centonze D, Petta F, Versace V, Rossi S, Torelli F, Prosperetti C, Rossi S, Marfia GA, Bernardi G, Koch G, Miano R, Boffa L, Finazzi-Agro E. Effects of motor cortex rTMS on lower urinary tract dysfunction in multiple sclerosis. Mult Scler. 2007 Mar;13(2):269-71. doi: 10.1177/1352458506070729. Epub 2007 Jan 29.

  PMID: 17439897 BACKGROUND

• Choksi D, Schott B, Tran K, Jang R, Hasan KM, Lincoln JA, Jalali A, Karmonik C, Salazar B, Khavari R. Disruption of specific white matter tracts is associated with neurogenic lower urinary tract dysfunction in women with multiple sclerosis. Neurourol Urodyn. 2023 Jan;42(1):239-248. doi: 10.1002/nau.25075. Epub 2022 Nov 2.

  PMID: 36321777 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 RESULT

• Jang Y, Tran K, Shi Z, Christof K, Choksi D, Salazar BH, Lincoln JA, Khavari R. Predictors for outcomes of noninvasive, individualized transcranial magnetic neuromodulation in multiple sclerosis women with neurogenic voiding dysfunction. Continence (Amst). 2022 Dec;4:100517. doi: 10.1016/j.cont.2022.100517. Epub 2022 Oct 19.

  PMID: 36568960 RESULT

• Shi Z, Karmonik C, Soltes A, Tran K, Lincoln JA, Boone T, Khavari R. Altered bladder-related brain network in multiple sclerosis women with voiding dysfunction. Neurourol Urodyn. 2022 Sep;41(7):1612-1619. doi: 10.1002/nau.25008. Epub 2022 Jul 17.

  PMID: 35842826 RESULT

• 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 DERIVED

MeSH Terms

Conditions

Urinary Bladder, Neurogenic; Multiple Sclerosis

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

Limitations and Caveats

This is a pilot study with a small sample size of 10 women and no controls. Other potential limitations of this study include the supine position during the fMRI/UDS examination, which could pose difficulty for subjects to void in the scanner. MS is a heterogeneous disease, and the observed changes in outcomes could be a result of historical changes unrelated to treatment, or depending on baseline factors such as location of lesion burdens or duration of MS.

Results Point of Contact

• Title: Rose Khavari, MD
• Organization: Houston Methodist Hospital

rkhavari@houstonmethodist.org

7134419118

Study Officials

• Rose Khavari, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Houston Methodist Hospital Urologist and Research Director

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: July 2, 2018
• Study Start: July 1, 2018
• Primary Completion: July 31, 2021
• Study Completion: July 31, 2022
• Last Updated: October 5, 2023
• Results First Posted: October 5, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)