Brain Targets in Patients With Bladder Emptying Difficulties

NCT ID: NCT03574610

Last Updated: 2023-10-05

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-01

Study Completion Date

2022-07-31

Brief Summary

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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

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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.

Conditions

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Neurogenic Bladder Multiple Sclerosis Voiding Dysfunction

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Subjects with Multiple Sclerosis and Voiding Dysfunction

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

Group Type EXPERIMENTAL

Transcranial Rotating Permanent Magnet Stimulator (TRPMS)

Intervention Type 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.

Interventions

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Transcranial Rotating Permanent Magnet Stimulator (TRPMS)

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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* 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

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

The Methodist Hospital Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Rose Khavari, M.D.

Principal Investigator, Houston Methodist Hospital Urologist and Research Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rose Khavari, MD

Role: PRINCIPAL_INVESTIGATOR

The Methodist Hospital Research Institute

Locations

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Houston Methodist Hospital

Houston, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 26067125 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19371782 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24769029 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27664581 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17293127 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16145475 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9827764 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9055802 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17439897 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36321777 (View on PubMed)

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.

Reference Type RESULT
PMID: 34694911 (View on PubMed)

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.

Reference Type RESULT
PMID: 36568960 (View on PubMed)

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.

Reference Type RESULT
PMID: 35842826 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33757581 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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K12DK083014

Identifier Type: NIH

Identifier Source: secondary_id

View Link

K23DK118209

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00019329

Identifier Type: -

Identifier Source: org_study_id

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