Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03574610
Other study ID # Pro00019329
Secondary ID K12DK083014K23DK
Status Completed
Phase N/A
First received
Last updated
Start date July 1, 2018
Est. completion date July 31, 2022

Study information

Verified date October 2023
Source The Methodist Hospital Research Institute
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 11
Est. completion date July 31, 2022
Est. primary completion date July 31, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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

Study Design


Intervention

Device:
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.

Locations

Country Name City State
United States Houston Methodist Hospital Houston Texas

Sponsors (2)

Lead Sponsor Collaborator
The Methodist Hospital Research Institute National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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) — View Citation

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. — View 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 — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Changes in Objective Clinical Outcomes Following Treatment The objective clinical assessment included changes in post void residual (PVR), voided volume (VV) and bladder capacity (BC) in participants after treatment as compared to baseline. PVR measures the volume of urine (cc/mL) that is left after voiding. VV measures the volume of urine that is voided (cc/mL). BC measures the volume of urine (cc/mL) the bladder has a capacity to hold, this value is calculated by adding the VV + PVR values obtained. Baseline, after treatment and 4 month follow up
Secondary Changes in %Post-Void Residual/Bladder Capacity (PVR/BC) Following Treatment Objective clinical assessments included changes in post void residual (PVR) and bladder capacity in participants after treatment. PVR measures the volume of urine (cc/mL) that is left after voiding. BC measures the volume of urine (cc/mL) the bladder has a capacity to hold. % PVR/BC measures how much of the overall volume is left after voiding, showing how efficient a voiding is before and after treatment. Baseline, after treatment and 4 month follow up
Secondary Changes in Non-instrumented Uroflow Variable Qmax Following Treatment The objective clinical assessment included changes in non-instrumented uroflow variables such as Qmax, in participants after treatment as compared to baseline. Qmax values reported here correspond to the peak urine flow (mL/s) seen during uroflowmetry testing. Baseline, after treatment and 4 month follow up
Secondary Changes in Liverpool Nomogram Following Treatment The objective clinical assessment included changes in non-instrumented uroflow variables such as Liverpool nomogram in participants after treatment as compared to baseline. The Liverpool nomogram provides normal reference ranges for the maximum and average urine flow rates over a wide range of voided volumes. It is presented as a percentile ranking depending on the flow rate and voided volume for each participant. Baseline, after treatment and 4 month follow-up
Secondary Changes in Subjective Clinical Outcomes Following Treatment - Urinary Distress Inventory, Short Form (UDI-6) Questionnaire Our subjective clinical assessment included changes in validated questionnaires. This assessment has 6 questions and is used to assess life quality and symptom distress for urinary incontinence in women. We report raw scores here for questions pertaining to voiding symptoms. Each question has the following score range: 0-4 (with the highest score associated with worse symptoms). Baseline, after treatment and 4 month follow up
Secondary Changes in Subjective Clinical Outcomes Following Treatment - American Urological Association Symptom Score (AUASS) Questionnaire Our subjective clinical assessment included changes in validated questionnaires. This assessment has 8 questions and is used to assess how bothersome urinary symptoms are and quality of life. We 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). Baseline, after treatment and 4 month follow up
Secondary Changes in Subjective Clinical Outcomes Following Treatment - Neurogenic Bladder Symptom Score (NBSS) Questionnaire Our subjective clinical assessment included 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). We report raw scores here for all domains and QoL. Baseline, after treatment and 4 month follow up
See also
  Status Clinical Trial Phase
Completed NCT05528666 - Risk Perception in Multiple Sclerosis
Completed NCT03608527 - Adaptive Plasticity Following Rehabilitation in Multiple Sclerosis N/A
Recruiting NCT05532943 - Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With Multiple Sclerosis Phase 1/Phase 2
Completed NCT02486640 - Evaluation of Potential Predictors of Adherence by Investigating a Representative Cohort of Multiple Sclerosis (MS) Patients in Germany Treated With Betaferon
Completed NCT01324232 - Safety and Efficacy of AVP-923 in the Treatment of Central Neuropathic Pain in Multiple Sclerosis Phase 2
Completed NCT04546698 - 5-HT7 Receptor Implication in Inflammatory Mechanisms in Multiple Sclerosis
Active, not recruiting NCT04380220 - Coagulation/Complement Activation and Cerebral Hypoperfusion in Relapsing-remitting Multiple Sclerosis
Completed NCT02835677 - Integrating Caregiver Support Into MS Care N/A
Completed NCT03686826 - Feasibility and Reliability of Multimodal Evoked Potentials
Recruiting NCT05964829 - Impact of the Cionic Neural Sleeve on Mobility in Multiple Sclerosis N/A
Withdrawn NCT06021561 - Orofacial Pain in Multiple Sclerosis
Completed NCT03653585 - Cortical Lesions in Patients With Multiple Sclerosis
Recruiting NCT04798651 - Pathogenicity of B and CD4 T Cell Subsets in Multiple Sclerosis N/A
Active, not recruiting NCT05054140 - Study to Evaluate Efficacy, Safety, and Tolerability of IMU-838 in Patients With Progressive Multiple Sclerosis Phase 2
Completed NCT05447143 - Effect of Home Exercise Program on Various Parameters in Patients With Multiple Sclerosis N/A
Recruiting NCT06195644 - Effect of Galvanic Vestibular Stimulation on Cortical Excitability and Hand Dexterity in Multiple Sclerosis Patients Phase 1
Completed NCT04147052 - iSLEEPms: An Internet-Delivered Intervention for Sleep Disturbance in Multiple Sclerosis N/A
Completed NCT03594357 - Cognitive Functions in Patients With Multiple Sclerosis
Completed NCT03591809 - Combined Exercise Training in Patients With Multiple Sclerosis N/A
Completed NCT02845635 - MS Mosaic: A Longitudinal Research Study on Multiple Sclerosis