Trial Outcomes & Findings for Central Nervous System Changes Following OnabotulinumtoxinA Injection in the Bladder (NCT NCT03033355)

NCT ID: NCT03033355

Last Updated: 2025-08-05

Results Overview

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.

• Recruitment status: COMPLETED
• Target enrollment: 12 participants
• Primary outcome timeframe: Baseline (pre-OnabotA) and 6-10 weeks post-OnabotA treatment
• Results posted on: 2025-08-05

Participant Flow

Participant milestones

Measure	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 Botulinum Toxin-A.
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Central Nervous System Changes Following OnabotulinumtoxinA Injection in the Bladder

Baseline characteristics by cohort

Measure	BTX-A Injection n=12 Participants 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.
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	10 Participants n=5 Participants
Age, Continuous	43.9 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants
Race/Ethnicity, Customized Declined	1 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Pre and Post BTX-A Injection n=12 Participants 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. Intra-detrusor injection of Onabotulinumtoxin-A: Using cystoscopy, Onabotulinumtoxin-A is injected into the bladder.	Post-OnabotA UDS Parameters The following metrics reflect the urodynamic assessments of participants following OnabotA treatment.
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment Right Cingulate Body	2.6 BOLD Signal Change Derived T-Value Interval -3.9 to 3.5	—
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment Left Posterior Cingulate	2.6 BOLD Signal Change Derived T-Value Interval -3.9 to 3.5	—
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment Left Anterior Cingulate	3.5 BOLD Signal Change Derived T-Value Interval -3.9 to 3.5	—
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment Right Prefrontal Cortex	2.6 BOLD Signal Change Derived T-Value Interval -3.9 to 3.5	—
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment Left Insula	2.6 BOLD Signal Change Derived T-Value Interval -3.9 to 3.5	—
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment Pons Micturition Center	2.4 BOLD Signal Change Derived T-Value Interval -3.9 to 3.5	—
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment Left Cerebellum	-3.9 BOLD Signal Change Derived T-Value Interval -3.9 to 3.5	—
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment Left Fusiform Gyrus	-3.1 BOLD Signal Change Derived T-Value Interval -3.9 to 3.5	—
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment Left Lentiform Nucleus	-2.1 BOLD Signal Change Derived T-Value Interval -3.9 to 3.5	—
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment Right Lentiform Nucleus	-2.6 BOLD Signal Change Derived T-Value Interval -3.9 to 3.5	—
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 Interval -3.9 to 3.5	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Pre and Post BTX-A Injection n=12 Participants 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. Intra-detrusor injection of Onabotulinumtoxin-A: Using cystoscopy, Onabotulinumtoxin-A is injected into the bladder.	Post-OnabotA UDS Parameters n=12 Participants The following metrics reflect the urodynamic assessments of participants following OnabotA treatment.
Changes in Urodynamic (UDS) Parameters Following OnabotA Treatment Final Post Void Residual (PVR) Volume	261.4 Cubic Centimeters Interval 70.0 to 650.0	377.9 Cubic Centimeters Interval 120.0 to 600.0
Changes in Urodynamic (UDS) Parameters Following OnabotA Treatment Maximum Cystometric Capacity (MCC) During 1st fMRI/UDS Bladder Filling	134.5 Cubic Centimeters Interval 14.0 to 251.0	195.5 Cubic Centimeters Interval 51.0 to 401.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Pre and Post BTX-A Injection n=12 Participants 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. Intra-detrusor injection of Onabotulinumtoxin-A: Using cystoscopy, Onabotulinumtoxin-A is injected into the bladder.	Post-OnabotA UDS Parameters n=12 Participants The following metrics reflect the urodynamic assessments of participants following OnabotA treatment.
Number of Participants Presenting With Neurogenic Detrusor Overactivity (NDO) Events During Urodynamic Studies (UDS) Before and After OnabotA Treatment	6 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Pre and Post BTX-A Injection n=12 Participants 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. Intra-detrusor injection of Onabotulinumtoxin-A: Using cystoscopy, Onabotulinumtoxin-A is injected into the bladder.	Post-OnabotA UDS Parameters n=12 Participants The following metrics reflect the urodynamic assessments of participants following OnabotA treatment.
Changes in Subjective Clinical Outcomes Following Treatment - Urogenital Distress Inventory, Short Form (UDI-6) UDI-6, Q2 (Urge Urinary Incontinence)	2.64 score on a scale Interval 0.0 to 4.0	1.1 score on a scale Interval 0.0 to 4.0
Changes in Subjective Clinical Outcomes Following Treatment - Urogenital Distress Inventory, Short Form (UDI-6) Total UDI-6 Score	12.09 score on a scale Interval 6.0 to 21.0	6.27 score on a scale Interval 0.0 to 15.0
Changes in Subjective Clinical Outcomes Following Treatment - Urogenital Distress Inventory, Short Form (UDI-6) UDI-6, Q1 (Frequency)	3.27 score on a scale Interval 2.0 to 4.0	1.55 score on a scale Interval 0.0 to 4.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Pre and Post BTX-A Injection n=12 Participants 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. Intra-detrusor injection of Onabotulinumtoxin-A: Using cystoscopy, Onabotulinumtoxin-A is injected into the bladder.	Post-OnabotA UDS Parameters n=12 Participants The following metrics reflect the urodynamic assessments of participants following OnabotA treatment.
Changes in Subjective Clinical Outcomes Following Treatment - Incontinence Impact Questionnaire Short Form (IIQ-7)	9.64 score on a scale Interval 0.0 to 18.0	4.36 score on a scale Interval 0.0 to 15.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Pre and Post BTX-A Injection n=12 Participants 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. Intra-detrusor injection of Onabotulinumtoxin-A: Using cystoscopy, Onabotulinumtoxin-A is injected into the bladder.	Post-OnabotA UDS Parameters n=12 Participants The following metrics reflect the urodynamic assessments of participants following OnabotA treatment.
Changes in Voiding Diary Metrics - Urge Urinary Incontinence (UUI) Events Per Day	1.64 Average events per day Interval 0.0 to 4.0	0.42 Average events per day Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Pre and Post BTX-A Injection n=12 Participants 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. Intra-detrusor injection of Onabotulinumtoxin-A: Using cystoscopy, Onabotulinumtoxin-A is injected into the bladder.	Post-OnabotA UDS Parameters n=12 Participants The following metrics reflect the urodynamic assessments of participants following OnabotA treatment.
Changes in Voiding Diary Metrics - Number of Participants Requiring Clean Intermittent Catheterization(CIC)	8 Participants	11 Participants

Adverse Events

Pre and Post BTX-A Injection

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Rose Khavari

houston methodist Hospital

Phone: 713-363-9154

Email: rkhavari@houstonmethodist.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place