Central Nervous System Changes Following OnabotulinumtoxinA Injection in the Bladder

A Prospective Study of Higher Neural Control Changes Following Intra-detrusor Injection of Onabotulinumtoxin-A in Patients With Multiple Sclerosis and Lower Urinary Tract Symptoms.

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03033355

Enrollment

Registered

2017-01-26

Start date

2014-02-28

Completion date

2019-03-31

Last updated

2025-08-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Detrusor, Overactive, Lower Urinary Tract Symptoms, Multiple Sclerosis, Neurogenic Bladder, Urge Incontinence

Keywords

Neurogenic Bladder, Detrusor Overactivity, Botox, fMRI

Brief summary

The purpose of this research study is to evaluate higher neural changes following intra-detrusor injection of Onabotulinumtoxin-A (BTX-A) in patients with Multiple Sclerosis (MS). We will use our prospectively collected cohort of patients. Concurrent Urodynamic and Functional Magnetic Resonance (fMRI) data will be recorded pre- and post-intravesical injection of BTX-A in patients with Multiple Sclerosis (MS) and neurogenic detrusor activity (NDO).

Detailed description

Multiple Sclerosis is a severe debilitating disease that affects patient's quality of life. Up to 90% of patients with MS will develop lower urinary tract dysfunction within the first 18 years of the disease. Lower urinary tract symptoms (LUTS) can range from urgency to urge urinary incontinence and/or hesitancy and incomplete bladder emptying. Urgency, frequency, and neurogenic detrusor overactivity (NDO) are the most common urologic findings (34-99%) during diagnostic evaluations of patients with MS. Even though anticholinergic or beta agonist drugs have limited effectiveness and adverse side effects, they are the first line pharmacotherapy for patients with NDO if behavioral modifications and pelvic floor physical therapy are unsuccessful. Onabotulinumtoxin-A (BTX-A) intra-detrusor injection is a highly effective treatment option for patients with NDO who are refractory to more conservative management. BTX-A blocks the release of acetylcholine at the neuromuscular junction and leads to a temporary chemodenervation of the bladder (paralysis of the muscle). Motor effects of BTX-A on the bladder have been extensively studied and widely reported in the literature, and the US Food and Drug Administration has approved BTX-A for the treatment of detrusor overactivity in neurogenic and non-neurogenic patients. However, the sensory effects of BTX-A injection correlating to central nervous system regional perception/localization of urgency, frequency, and urge incontinence in humans are not well known. Over the past decades, functional MRI (fMRI) has been used to study the activation of supraspinal lower urinary tract control centers in healthy subjects during the storage and voiding phases. Given these facts, the investigators are interested in evaluating the role of intra-detrusor injection of BTX-A in afferent response in patients with MS and NDO. High-resolution neuroimaging techniques will help investigators to further understand how MS affects the bladder-brain controls. This study will use fMRI and task-related blood oxygen level dependent (BOLD) signal to evaluate patients with MS and NDO prior to, and 6-10 weeks after intra-detrusor injection of BTX-A with simultaneous urodynamic evaluation. Clinical correlation between women with these chronic urologic problems and new discoveries at level of central nervous system activity will give a better understanding of this disorder, leading to the development of more effective diagnostic and treatment modalities.

Interventions

DRUGIntra-detrusor injection of Onabotulinumtoxin-A

Using cystoscopy, Onabotulinumtoxin-A is injected into the bladder.

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

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, spina bifida, Parkinson's, major spine surgery). * 18 years or older. * Female patients.

Exclusion criteria

* Male * History of any incontinence surgery (sling, Marshall-Marchetti-Krantz Procedure, Burch). * History of any lower urinary tract surgery or manipulation (urethral dilation). * Positive urine pregnancy test at enrollment .

Design outcomes

Primary

Measure	Time frame	Description
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Baseline (pre-OnabotA) and 6-10 weeks post-OnabotA treatment	Brain activation patterns associated with the strong desire to void (Full Urge) were examined using functional magnetic resonance imaging (fMRI), assessing BOLD signal intensity in predefined regions of interest at baseline and 6-10 weeks following OnabotulinumtoxinA (OnabotA) injection. Post-treatment changes in activity (voxel signal) were analyzed based on a statistical threshold, with increased activation defined by a T-value greater than or equal to 2.0 and decreased activation by a T-value less than or equal to 2.0.

Secondary

Measure	Time frame	Description
Number of Participants Presenting With Neurogenic Detrusor Overactivity (NDO) Events During Urodynamic Studies (UDS) Before and After OnabotA Treatment	Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment	This outcome measure assesses the incidence of neurogenic detrusor overactivity (NDO) events observed during fMRI/UDS sessions conducted at baseline (pre-OnabotA) and 6-10 weeks following OnabotA treatment. Detrusor overactivity refers to involuntary detrusor muscle contractions observed during the bladder filling phase, which may be spontaneous or provoked. In individuals with neurogenic lower urinary tract dysfunction, these involuntary contractions are attributed to underlying neurologic conditions and are classified as NDO. The presence or absence of NDO events was determined based on detrusor pressure tracings recorded during the bladder filling phase. Participants were categorized as positive for NDO if one or more involuntary contractions were observed. A decrease in the number of participants with NDO events following OnabotA treatment suggests a therapeutic effect on detrusor overactivity and may indicate improved bladder control and reduced urgency or incontinence symptoms.
Changes in Subjective Clinical Outcomes Following Treatment - Urogenital Distress Inventory, Short Form (UDI-6)	Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment	The Urinary Distress Inventory, Short Form (UDI-6), is a validated questionnaire used to assess the severity of urinary symptoms and their impact on quality of life. It consists of six items evaluating urinary frequency, urgency-related leakage, stress-related leakage, difficulty emptying the bladder, and discomfort or pain in the lower abdomen or genital area. Each item is scored on a Likert scale (0-4), with higher scores indicating greater symptom-related distress.Total UDI-6 scores are calculated by adding all 6 questions with scores ranging from 0 to 24, where higher scores indicate worse symptoms. In this study, we report overall UDI-6 total scores (range: 0-24) as well as individual scores (range:0-4) for Questions 1 (urinary frequency) and 2 (urge urinary incontinence) at two timepoints: baseline (pre-OnabotA) and 6-10 weeks following OnabotA treatment.
Changes in Urodynamic (UDS) Parameters Following OnabotA Treatment	Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment	Objective clinical assessments examined changes in urodynamic (UDS) parameters collected during functional MRI (fMRI) sessions at baseline (pre-OnabotA) and 6-10 weeks post-treatment. These included final post-void residual (PVR) volume and maximum cystometric capacity (MCC). MCC was measured during the first bladder infusion cycle of each neuroimaging session and represents the bladder volume at which an individual can no longer delay voiding during bladder filling. An increase in MCC following OnabotA treatment may indicate improved bladder storage capacity, particularly in individuals with reduced bladder compliance or capacity. PVR reflects the volume of urine remaining in the bladder after voiding (measured in CC or mL); higher PVR values suggest less effective bladder emptying.
Changes in Voiding Diary Metrics - Urge Urinary Incontinence (UUI) Events Per Day	Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment	Voiding diary entries recorded that measure the number of urge urinary incontinence (UUI) events per day. Recorded timepoints (Pre- and Post-OnabotA treatment). Measures are reported by participants that fill out voiding diaries at baseline (pre-) and post-OnabotA treatment timepoints.
Changes in Voiding Diary Metrics - Number of Participants Requiring Clean Intermittent Catheterization(CIC)	Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment	Analysis of voiding diary metric measuring the number of participants that utilized clean intermittent catheterization (CIC) to empty their bladder. These measures were recorded at both baseline (pre-) and post-OnabotA treatment timepoints.
Changes in Subjective Clinical Outcomes Following Treatment - Incontinence Impact Questionnaire Short Form (IIQ-7)	Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment	The Incontinence Impact Questionnaire Short Form (IIQ-7) is a seven-item questionnaire used to assess the impact of urinary incontinence on a person's quality of life. Each question has the following score range: 0-3 (with the highest score associated with higher symptom distress). Here we report the average overall score, which is calculated by adding scores from all 7 questions. Total score ranges from 0 to 21, with higher scores reflecting worse symptoms.

Countries

United States

Participant flow

Participants by arm

Arm	Count
BTX-A Injection Female patients with confirmed diagnosis of Multiple Sclerosis referred to our Neuro-urology clinic with neurogenic lower urinary tract dysfunction receiving intra-detrusor injection of Onabotulinumtoxin-A.	12
Total	12

Baseline characteristics

Characteristic	BTX-A Injection
Age, Continuous	43.9 years
Race/Ethnicity, Customized Black	1 Participants
Race/Ethnicity, Customized Caucasian	10 Participants
Race/Ethnicity, Customized Declined	1 Participants
Region of Enrollment United States	12 participants
Sex: Female, Male Female	12 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 12
other Total, other adverse events	0 / 12
serious Total, serious adverse events	0 / 12

Outcome results

Primary

Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment

Brain activation patterns associated with the strong desire to void (Full Urge) were examined using functional magnetic resonance imaging (fMRI), assessing BOLD signal intensity in predefined regions of interest at baseline and 6-10 weeks following OnabotulinumtoxinA (OnabotA) injection. Post-treatment changes in activity (voxel signal) were analyzed based on a statistical threshold, with increased activation defined by a T-value greater than or equal to 2.0 and decreased activation by a T-value less than or equal to 2.0.

Time frame: Baseline (pre-OnabotA) and 6-10 weeks post-OnabotA treatment

Arm	Measure	Group	Value (MEAN)
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Left Fusiform Gyrus	-3.1 BOLD Signal Change Derived T-Value
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Right Cingulate Body	2.6 BOLD Signal Change Derived T-Value
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Left Posterior Cingulate	2.6 BOLD Signal Change Derived T-Value
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Left Anterior Cingulate	3.5 BOLD Signal Change Derived T-Value
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Right Prefrontal Cortex	2.6 BOLD Signal Change Derived T-Value
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Left Insula	2.6 BOLD Signal Change Derived T-Value
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Pons Micturition Center	2.4 BOLD Signal Change Derived T-Value
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Left Cerebellum	-3.9 BOLD Signal Change Derived T-Value
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Left Lentiform Nucleus	-2.1 BOLD Signal Change Derived T-Value
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Right Lentiform Nucleus	-2.6 BOLD Signal Change Derived T-Value
Pre and Post BTX-A Injection	Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment	Left Amygdala/parahippocampal Gyrus	-2.0 BOLD Signal Change Derived T-Value

Comparison: Right Cingulate Bodyp-value: 0.0012Student t-Test

Comparison: Left Posterior Cingulatep-value: 0.02student t-test

Comparison: Left Anterior Cingulatep-value: 0.0015student t-test

Comparison: Right Prefrontal Cortexp-value: 0.0015student t-test

Comparison: Left Insulap-value: 0.0138student t-test

Comparison: Pons Micturition Centerp-value: 0.049student t-test

Comparison: Left Cerebellump-value: 0.001student t-test

Comparison: Left Lentiform Nucleusp-value: 0.026student t-test

Comparison: Right Lentiform Nucleusp-value: 0.026student t-test

Comparison: Left Amygdala/parahippocampal Gyrusp-value: 0.015student t-test

Secondary

Changes in Subjective Clinical Outcomes Following Treatment - Incontinence Impact Questionnaire Short Form (IIQ-7)

The Incontinence Impact Questionnaire Short Form (IIQ-7) is a seven-item questionnaire used to assess the impact of urinary incontinence on a person's quality of life. Each question has the following score range: 0-3 (with the highest score associated with higher symptom distress). Here we report the average overall score, which is calculated by adding scores from all 7 questions. Total score ranges from 0 to 21, with higher scores reflecting worse symptoms.