Multiple SclerosisNCT03033355
Central Nervous System Changes Following OnabotulinumtoxinA Injection in the Bladder
An observational study of Multiple Sclerosis and Lower Urinary Tract Symptoms, run by The Methodist Hospital Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Multiple Sclerosis, Lower Urinary Tract Symptoms, Neurogenic Bladder
- What is being tested?
- Intra-detrusor injection of Onabotulinumtoxin-A
- Type of treatment
- Injection or infusion
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to Mar 2019
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Female subjects diagnosed with Multiple Sclerosis and lower urinary tract symptoms who are refractory to conservative management for neurogenic detrusor overactivity.
Who may be able to join
- 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.
Who cannot join
- 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 .
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
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).
Read the 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.
- Conditions
- Multiple Sclerosis, Lower Urinary Tract Symptoms, Neurogenic Bladder, Detrusor, Overactive, Urge Incontinence
- Being tested
- Intra-detrusor injection of Onabotulinumtoxin-A
- Keywords
- Neurogenic Bladder, Detrusor Overactivity, Botox, fMRI
- Medical subject headings
- Multiple Sclerosis, Lower Urinary Tract Symptoms, Urinary Bladder, Neurogenic, Urinary Bladder, Overactive, Urinary Incontinence, Urge
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intra-detrusor injection of Onabotulinumtoxin-ADrug
Also called OnabotulinumtoxinA, Botox®
Using cystoscopy, Onabotulinumtoxin-A is injected into the bladder.
| Study group | Role | What they receive |
|---|---|---|
| Pre and post 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. Receives: Drug: Intra-detrusor injection of Onabotulinumtoxin-A |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (pre-OnabotA) and 6-10 weeks post-OnabotA treatment
Secondary outcomes (6)
Changes in Urodynamic (UDS) Parameters Following 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.
Measured: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Number of Participants Presenting With Neurogenic Detrusor Overactivity (NDO) Events During Urodynamic Studies (UDS) Before and After 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.
Measured: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Changes in Subjective Clinical Outcomes Following Treatment - Urogenital Distress Inventory, Short Form (UDI-6)
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.
Measured: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
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.
Measured: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Changes in Voiding Diary Metrics - Urge Urinary Incontinence (UUI) Events Per Day
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.
Measured: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Changes in Voiding Diary Metrics - Number of Participants Requiring Clean Intermittent Catheterization(CIC)
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.
Measured: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2017 (estimated)
- Study startFeb 2014
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rose Khavari, M.D., The Methodist Hospital Research Institute
- Investigators
- Rose Khavari, MD, Principal investigator, The Methodist Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03033355
- Sponsor's protocol ID
- Pro00010110
- Status last verified
- Jul 2025
- First submitted
- 15 Jul 2016
- Last updated
- 5 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT03033355
- Acronym / sponsor ID
- Pro00010110
- Conditions
- Multiple Sclerosis, Lower Urinary Tract Symptoms, Neurogenic Bladder, Detrusor, Overactive, Urge Incontinence
- Keywords
- Neurogenic Bladder, Detrusor Overactivity, Botox, fMRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Study start
- Feb 2014 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 26 Jan 2017 (estimated)
- Results
- Posted 5 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pre and post BTX-A injection | – | Drug: Intra-detrusor injection of Onabotulinumtoxin-AFemale 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Female subjects diagnosed with Multiple Sclerosis and lower urinary tract symptoms who are refractory to conservative management for neurogenic detrusor overactivity.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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 .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intra-detrusor injection of Onabotulinumtoxin-AAlso: OnabotulinumtoxinA, Botox®Using cystoscopy, Onabotulinumtoxin-A is injected into the bladder. | Drug | Pre and post BTX-A injection |
Primary outcome
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment
Time frame: 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.
6 secondary outcomes
Changes in Urodynamic (UDS) Parameters Following OnabotA Treatment
Time frame: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Number of Participants Presenting With Neurogenic Detrusor Overactivity (NDO) Events During Urodynamic Studies (UDS) Before and After OnabotA Treatment
Time frame: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Changes in Subjective Clinical Outcomes Following Treatment - Urogenital Distress Inventory, Short Form (UDI-6)
Time frame: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Changes in Subjective Clinical Outcomes Following Treatment - Incontinence Impact Questionnaire Short Form (IIQ-7)
Time frame: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Changes in Voiding Diary Metrics - Urge Urinary Incontinence (UUI) Events Per Day
Time frame: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Changes in Voiding Diary Metrics - Number of Participants Requiring Clean Intermittent Catheterization(CIC)
Time frame: Baseline (Pre-OnabotA) and 6-10 Weeks Post-OnabotA Treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rose Khavari, MD principal investigator
The Methodist Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis and Lower Urinary Tract Symptoms, run by The Methodist Hospital Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Blood Oxygen Level Dependent (BOLD) Signals in the Brain After Treatment (time frame: Baseline (pre-OnabotA) and 6-10 weeks post-OnabotA treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2025.