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Study Protocol
Therapeutic Effects of Noninvasive, Individualized, Transcranial Neuromodulation Treatment for Voiding Dysfunction in Multiple Sclerosis Patients: Study Protocol for a Pilot Clinical Trial
Khue Tran
Houston Methodist Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6836-2591
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Voiding dysfunction (VD) is a common neurogenic lower urinary tract dysfunction (NLUTD) in multiple sclerosis (MS) patients. Currently, the only effective management for VD and urinary retention in MS patients is catheterization, prompting us to look for novel therapeutic options beyond the bladder, such as the brain. Transcranial rotating permanent magnet stimulator (TRPMS) is a noninvasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions, enhancing or attenuating strengths of functional connections between these regions. The objective of this pilot clinical trial is to evaluate the therapeutic effects of TRPMS in modulating brain regions during voiding initiation and mitigating VD in female MS individuals.
Methods: Ten adult female MS patients with VD (defined as having %post-void residual/bladder capacity (%PVR/BC) ≥ 40% or Liverpool nomogram percentile < 10%) will be recruited for this study. Concurrent urodynamic and functional MRI evaluation with a bladder filling/emptying task repeated three to four times will be performed at baseline and post-treatment. Predetermined regions of interest and their blood-oxygen-level-dependent (BOLD) activation at voiding initiation will be identified on each patient’s baseline anatomical and functional MRI scan, corresponding to the microstimulators placement on their individualized TRPMS treatment cap to either stimulate or inhibit these regions. Patients will receive ten 40-minute treatment sessions. Non-instrumented uroflow and validated questionnaires will also be collected at baseline and post-treatment to evaluate clinical improvement.
Discussion: Despite the crucial role of the central nervous system in urinary control and its sensitivity to MS, there has been no treatment for urinary dysfunction targeting the brain centers that are involved in proper bladder function. This trial, to our knowledge, will be the first of its kind in humans to consider non-invasive and individualized cortical modulation for treating VD in MS patients. Results from this study will provide a better understanding of the brain control of neurogenic bladders and lay the foundation for a potential alternative therapy for VD in MS patients and other NLUTD in a larger neurogenic population in the future.
Trial registration: This trial is registered at ClinicalTrials.Gov (NCT03574610, July 2, 2018, https://clinicaltrials.gov/ct2/show/NCT03574610) and Houston Methodist Research Institute IRB (PRO00019329).
Keywords
multiple sclerosis, voiding dysfunction, fMRI, neuromodulation, urodynamics, urinary retention
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This preprint is under consideration at Pilot and Feasibility Studies. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Study Protocol
Therapeutic Effects of Noninvasive, Individualized, Transcranial Neuromodulation Treatment for Voiding Dysfunction in Multiple Sclerosis Patients: Study Protocol for a Pilot Clinical Trial
Khue Tran
Houston Methodist Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6836-2591
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 07 Jan, 2021
No community comments so far
Editor assigned
On 31 Dec, 2020
Editor invited
On 31 Dec, 2020
Submission checks complete
On 31 Dec, 2020
First submitted
On 28 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Voiding dysfunction (VD) is a common neurogenic lower urinary tract dysfunction (NLUTD) in multiple sclerosis (MS) patients. Currently, the only effective management for VD and urinary retention in MS patients is catheterization, prompting us to look for novel therapeutic options beyond the bladder, such as the brain. Transcranial rotating permanent magnet stimulator (TRPMS) is a noninvasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions, enhancing or attenuating strengths of functional connections between these regions. The objective of this pilot clinical trial is to evaluate the therapeutic effects of TRPMS in modulating brain regions during voiding initiation and mitigating VD in female MS individuals.
Methods: Ten adult female MS patients with VD (defined as having %post-void residual/bladder capacity (%PVR/BC) ≥ 40% or Liverpool nomogram percentile < 10%) will be recruited for this study. Concurrent urodynamic and functional MRI evaluation with a bladder filling/emptying task repeated three to four times will be performed at baseline and post-treatment. Predetermined regions of interest and their blood-oxygen-level-dependent (BOLD) activation at voiding initiation will be identified on each patient’s baseline anatomical and functional MRI scan, corresponding to the microstimulators placement on their individualized TRPMS treatment cap to either stimulate or inhibit these regions. Patients will receive ten 40-minute treatment sessions. Non-instrumented uroflow and validated questionnaires will also be collected at baseline and post-treatment to evaluate clinical improvement.
Discussion: Despite the crucial role of the central nervous system in urinary control and its sensitivity to MS, there has been no treatment for urinary dysfunction targeting the brain centers that are involved in proper bladder function. This trial, to our knowledge, will be the first of its kind in humans to consider non-invasive and individualized cortical modulation for treating VD in MS patients. Results from this study will provide a better understanding of the brain control of neurogenic bladders and lay the foundation for a potential alternative therapy for VD in MS patients and other NLUTD in a larger neurogenic population in the future.
Trial registration: This trial is registered at ClinicalTrials.Gov (NCT03574610, July 2, 2018, https://clinicaltrials.gov/ct2/show/NCT03574610) and Houston Methodist Research Institute IRB (PRO00019329).
Figure 1
Figure 2
Figure 3