Lower Urinary Tract Symptoms, Neurogenic Bladder, Neurogenic Detrusor Overactivity, Neuro: Neurogenic Bladder, Overactive Bladder
Conditions
Keywords
neurogenic bladder, Lower urinary tract symptoms, Neurogenic detrusor overactivity, Onabotulinum toxinA
Brief summary
The purpose of this study is to evaluate and standardize the way providers perform OnabotulinumtoxinA (BTX-A) injections into the bladder for the diagnosis of neurogenic lower urinary tract dysfunction (NLUTD)/overactive bladder (OAB). NLUTD/OAB is a syndrome that affects many people, and includes urinary frequency, urinary urgency, urgency incontinence, and nocturia. This syndrome can be challenging to treat and often requires procedural management - including BTX-A injections into the bladder.
Detailed description
Neurological disorders such as Multiple Sclerosis (MS), Spinal Cord Injury (SCI), Parkinson's Disease (PD), Spina Bifida (SB), and stroke disrupt neural control of voiding and lead to the development of neurogenic lower urinary tract dysfunction (NLUTD), which develops when either the detrusor muscle fails to maintain effective contractions (voiding phase) or fails to relax appropriately with low pressures (storage phase), if the urethral sphincter (internal or external) fails to lower its tonicity and resistance, or if there is an asynchrony in events eventually leading to detrusor sphincter dyssynergia (DSD). Different patterns of NLUTD (including both storage and voiding) can arise depending on the level of injury or type of neurological disease. It can be characterized by urinary urgency, frequency and incontinence or urinary hesitancy and retention that leads to urinary tract infections (UTIs). Some patients develop neurogenic overactive bladder (NOAB). Management of NOAB symptoms is complex. Treatment with BTX-A has been shown to decrease episodes of urinary incontinence and improve quality of life in this population. It has also been shown to ameliorate a multitude of devastating complications, such as upper tract deterioration, recurrent urinary tract infections, sepsis, and death. According to the current manufacturer's recommendation, a standard 200-unit vial of Botox® should be diluted in 30cc of 0.9% saline and injected across 30 different sites in the detrusor muscle (Figure 2). Despite these guidelines, there are wide variations in administration techniques, raising the question what is the best depth and location for injection, and optimal concentration and volume of toxin per injection site. The objective of this study is to determine the optimal injection schema for 200 units or more of intradetrusor BTX-A in patients with NOAB in the office setting. The investigators hypothesize that patients with NOAB symptoms undergoing intradetrusor injection of 200 units (or more) of BTX-A will be more willing to pursue additional sessions of BTX-A injections with a protocol utilizing less injection sites, while still maintaining effectiveness of the procedure.
Interventions
PROCEDUREStandard number of injection sites
200 units or 300 units BTX-A reconstituted in 20 mL normal saline, injected into the bladder detrusor in 20 separate injections of 1 mL including the trigone.
PROCEDUREReduced number of injection sites
200 units or 300 units BTX-A reconstituted in 5 mL normal saline, injected into the bladder detrusor in 5 separate injections of 1 mL including the trigone.
Sponsors
Collaborating for Advancement of Interdisciplinary Research in Benign Urology
The Methodist Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult men and women (\>18 years of age) with a diagnosis of neurological conditions such as MS, PD, CVA, myelomeningocele, SCI, or traumatic brain injury longer than 6 months prior to treatment. * Diagnosis of neurogenic bladder indicated for treatment with BTX-A for OAB symptoms. * Participants must be able to provide informed consent, as well as understand and be willing to undergo. follow-up procedures and completion of all questionnaires provided during the study.
Exclusion criteria
* Symptomatic UTI at the time of procedure, defined as positive nitrites or high-volume leukocyte esterase on urine dip in addition to at least one of the following symptoms: dysuria, gross hematuria, suprapubic pain, frequency/urgency above baseline. * Diagnosis of bladder pain syndrome or other chronic pain syndrome including fibromyalgia, chronic pelvic pain, pelvic floor dysfunction, levator myalgia. * Untreated bladder malignancy. * Women who are currently pregnant or breast feeding. * Contraindications to intradetrusor BTX-A injections.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Willingness to Repeat Procedure | Immediately post-procedure and 6 weeks post-procedure | Participants were asked to rate their willingness to repeat the procedure using an 11-point visual analog scale (VAS). A score of 0 (Never) indicates complete unwillingness, representing the least favorable outcome, while a score of 11 (Definitely) reflects strong willingness, representing the most favorable outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Neurogenic Bladder Symptoms After BTX-A Treatment - International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) | Baseline and 6-weeks after BTX-A injections | The ICIQ-SF is a standardized survey that assesses the frequency, severity, and impact of urinary incontinence (UI) on quality of life (QoL). The total score, ranging from 0 to 21, is calculated from three questions, with higher scores indicating more severe symptoms. A score of 0 reflects no leakage and no impact on QoL. Question 1 measures how often leakage occurs (0-5), Question 2 assesses the amount of leakage (0-6), and Question 3 evaluates the impact on QoL (0-10), with higher scores indicating worse outcomes. We report the mean difference in total ICIQ and QoL scores from baseline to 6-weeks post-treatment. |
| Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Baseline and 6-weeks after BTX-A injections | The NBSS-SF is a validated survey with 10 questions that measure bladder symptoms across 3 different domains: incontinence (score range: 0-12), storage and voiding (score range: 0-9), and consequences (score range: 0-7); the highest score is associated with worse symptoms. It also includes one question to assess overall quality of life (QoL) scored from 0 (pleased) to 4 (unhappy). The total score, ranging from 0 to 28, is calculated from the three domains (Q3-Q10), with 0 being the best outcome and 28 the worst outcome. Here we report the mean difference in total NBSS-SF, each of the domains and QoL scores from baseline to 6-weeks post-treatment. The NBSS-SF is a validated 10-question survey that assesses bladder symptoms across three domains: incontinence (score range: 0-12), storage and voiding (score range: 0-9), and consequences (score range: 0-7), with higher scores indicating worse symptoms. It also includes a quality of life (QoL) question (Q2) scored from 0 (pleased) |
| Patient Impression of Clinical Improvement After BTX-A - Patient Global Impression of Improvement (PGI-I) Scale | 6 weeks after BTX-A injection | The PGI-I is a validated tool for assessing patient satisfaction after therapy. It consists of a single question using a Likert scale to measure perceived improvement or worsening after BTX-A treatment, ranging from 1 (Very much worse) to 7 (Very much better). Data reported here reflect average scores obtained at the six-week follow-up. |
| Patient Reported Procedural Discomfort - Numeric Pain Rating Scale (NPRS) | Prior to and immediately after BTX-A injections | Participants rated their pain using the NPRS to assess discomfort during the BTX-A procedure. The NPRS is an 11-point scale (0-10), where 0 represents no pain and 10 indicates the worst pain ever experienced. Higher scores reflect greater pain intensity. We report the change in NPRS scores from before to immediately after the procedure. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Injection Sites (20) Standard number of injection sites: 200 units or 300 units BTX-A reconstituted in 20 mL normal saline, injected into the bladder detrusor in 20 separate injections of 1 mL including the trigone. | 39 |
| Reduced Injection Sites (5) Reduced number of injection sites: 200 units or 300 units BTX-A reconstituted in 5 mL normal saline, injected into the bladder detrusor in 5 separate injections of 1 mL including the trigone. | 39 |
| Total | 78 |
Baseline characteristics
| Characteristic | Standard Injection Sites (20) | Reduced Injection Sites (5) | Total |
|---|---|---|---|
| Age, Continuous | 50.2 years STANDARD_DEVIATION 22.2 | 47.7 years STANDARD_DEVIATION 19.4 | 48.95 years STANDARD_DEVIATION 20.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 9 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 28 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Medical comorbidities Cerebral Vascular Accident | 1 participants | 4 participants | 5 participants |
| Medical comorbidities Chronic Inflammatory Demyelinating Polyneuropathy | 1 participants | 0 participants | 1 participants |
| Medical comorbidities Multiple Sclerosis | 8 participants | 7 participants | 15 participants |
| Medical comorbidities Parkinsons Disease | 1 participants | 0 participants | 1 participants |
| Medical comorbidities Sacral Agenesis | 1 participants | 1 participants | 2 participants |
| Medical comorbidities Spina Bifida | 15 participants | 11 participants | 26 participants |
| Medical comorbidities Spinal Cord Injury | 4 participants | 11 participants | 15 participants |
| Medical comorbidities Syringomyelia | 0 participants | 1 participants | 1 participants |
| Medical comorbidities Transverse Myelitis | 0 participants | 2 participants | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) White | 27 Participants | 33 Participants | 60 Participants |
| Sex: Female, Male Female | 31 Participants | 28 Participants | 59 Participants |
| Sex: Female, Male Male | 8 Participants | 11 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 26 |
| other Total, other adverse events | 7 / 28 | 8 / 26 |
| serious Total, serious adverse events | 0 / 28 | 0 / 26 |
Outcome results
Primary
Willingness to Repeat Procedure
Participants were asked to rate their willingness to repeat the procedure using an 11-point visual analog scale (VAS). A score of 0 (Never) indicates complete unwillingness, representing the least favorable outcome, while a score of 11 (Definitely) reflects strong willingness, representing the most favorable outcome.
Time frame: Immediately post-procedure and 6 weeks post-procedure
Population: Data at 6-weeks post-procedure were available for 54 participants. Loss to follow-up included 10 participants from the 20-injection group and 12 participants from the 5-injection group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Injection Sites (20) | Willingness to Repeat Procedure | Post-injection willingness to repeat procedure rating (VAS score) | 9.16 units on a scale | Standard Deviation 1.46 |
| Standard Injection Sites (20) | Willingness to Repeat Procedure | 6-weeks post-procedure willingness to repeat procedure rating (VAS score) | 9.73 units on a scale | Standard Deviation 1.12 |
| Reduced Injection Sites (5) | Willingness to Repeat Procedure | Post-injection willingness to repeat procedure rating (VAS score) | 9.34 units on a scale | Standard Deviation 1.26 |
| Reduced Injection Sites (5) | Willingness to Repeat Procedure | 6-weeks post-procedure willingness to repeat procedure rating (VAS score) | 9.67 units on a scale | Standard Deviation 0.99 |
Comparison: Willingness to repeat procedure immediately after received intradetrusor BTX-A injectionsp-value: 0.57t-test, 2 sided
Comparison: Willingness to repeat procedure asses 6-weeks after intradetrusor BTX-A injectionsp-value: 0.83t-test, 2 sided
Secondary
Change in Neurogenic Bladder Symptoms After BTX-A Treatment - International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF)
The ICIQ-SF is a standardized survey that assesses the frequency, severity, and impact of urinary incontinence (UI) on quality of life (QoL). The total score, ranging from 0 to 21, is calculated from three questions, with higher scores indicating more severe symptoms. A score of 0 reflects no leakage and no impact on QoL. Question 1 measures how often leakage occurs (0-5), Question 2 assesses the amount of leakage (0-6), and Question 3 evaluates the impact on QoL (0-10), with higher scores indicating worse outcomes. We report the mean difference in total ICIQ and QoL scores from baseline to 6-weeks post-treatment.
Time frame: Baseline and 6-weeks after BTX-A injections
Population: Data at 6-weeks post-procedure were available for 54 participants. Loss to follow-up included 10 participants from the 20-injection group and 12 participants from the 5-injection group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Injection Sites (20) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) | Mean difference in Total ICIQ score | -4.11 units on a scale | Standard Deviation 8.25 |
| Standard Injection Sites (20) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) | Mean difference in ICIQ QoL score | -2.33 units on a scale | Standard Deviation 4.38 |
| Reduced Injection Sites (5) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) | Mean difference in Total ICIQ score | -5.23 units on a scale | Standard Deviation 6.55 |
| Reduced Injection Sites (5) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) | Mean difference in ICIQ QoL score | -3.54 units on a scale | Standard Deviation 3.7 |
Comparison: Difference in total ICIQ-SF score assessed before and 6-weeks after treatmentp-value: 0.59t-test, 2 sided
Comparison: Difference in ICIQ QoL score assessed before and 6-weeks after treatmentp-value: 0.29t-test, 2 sided
Secondary
Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF)
The NBSS-SF is a validated survey with 10 questions that measure bladder symptoms across 3 different domains: incontinence (score range: 0-12), storage and voiding (score range: 0-9), and consequences (score range: 0-7); the highest score is associated with worse symptoms. It also includes one question to assess overall quality of life (QoL) scored from 0 (pleased) to 4 (unhappy). The total score, ranging from 0 to 28, is calculated from the three domains (Q3-Q10), with 0 being the best outcome and 28 the worst outcome. Here we report the mean difference in total NBSS-SF, each of the domains and QoL scores from baseline to 6-weeks post-treatment. The NBSS-SF is a validated 10-question survey that assesses bladder symptoms across three domains: incontinence (score range: 0-12), storage and voiding (score range: 0-9), and consequences (score range: 0-7), with higher scores indicating worse symptoms. It also includes a quality of life (QoL) question (Q2) scored from 0 (pleased)
Time frame: Baseline and 6-weeks after BTX-A injections
Population: Data at 6-weeks post-procedure were available for 54 participants. Loss to follow-up included 10 participants from the 20-injection group and 12 participants from the 5-injection group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Injection Sites (20) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Mean difference in NBSS-SF QoL | -1.81 units on a scale | Standard Deviation 1.54 |
| Standard Injection Sites (20) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Mean difference in NBSS-SF storage and voiding domain | -2.96 units on a scale | Standard Deviation 2.47 |
| Standard Injection Sites (20) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Mean difference in NBSS-SF incontinence domain | -2.93 units on a scale | Standard Deviation 2.92 |
| Standard Injection Sites (20) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Mean difference in NBSS-SF consequence domain | -2.63 units on a scale | Standard Deviation 2.41 |
| Standard Injection Sites (20) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Mean difference in Total NBSS-SF | 5.44 units on a scale | Standard Deviation 4.19 |
| Reduced Injection Sites (5) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Mean difference in NBSS-SF consequence domain | -3.00 units on a scale | Standard Deviation 3.19 |
| Reduced Injection Sites (5) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Mean difference in Total NBSS-SF | 4.65 units on a scale | Standard Deviation 5.46 |
| Reduced Injection Sites (5) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Mean difference in NBSS-SF QoL | -2.15 units on a scale | Standard Deviation 1.46 |
| Reduced Injection Sites (5) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Mean difference in NBSS-SF incontinence domain | -2.15 units on a scale | Standard Deviation 1.46 |
| Reduced Injection Sites (5) | Change in Neurogenic Bladder Symptoms After BTX-A Treatment - Neurogenic Bladder Symptom Score - Short Form (NBSS-SF) | Mean difference in NBSS-SF storage and voiding domain | -3.04 units on a scale | Standard Deviation 3.39 |
Comparison: Difference in total NBSS-SF score assessed before and 6-weeks after treatmentp-value: 0.57t-test, 2 sided
Comparison: Difference in NBSS-SF QoL score assessed before and 6-weeks after treatmentp-value: 0.42t-test, 2 sided
Comparison: Difference in NBSS-SF incontinence domain score assessed before and 6-weeks after treatmentp-value: 0.24t-test, 2 sided
Comparison: Difference in NBSS-SF storage and voiding domain score assessed before and 6-weeks after treatmentp-value: 0.93t-test, 2 sided
Comparison: Difference in NBSS-SF consequences domain score assessed before and 6-weeks after treatmentp-value: 0.64t-test, 2 sided
Secondary
Patient Impression of Clinical Improvement After BTX-A - Patient Global Impression of Improvement (PGI-I) Scale
The PGI-I is a validated tool for assessing patient satisfaction after therapy. It consists of a single question using a Likert scale to measure perceived improvement or worsening after BTX-A treatment, ranging from 1 (Very much worse) to 7 (Very much better). Data reported here reflect average scores obtained at the six-week follow-up.
Time frame: 6 weeks after BTX-A injection
Population: Data at 6-weeks post-procedure were available for 54 participants. Loss to follow-up included 10 participants from the 20-injection group and 12 participants from the 5-injection group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Injection Sites (20) | Patient Impression of Clinical Improvement After BTX-A - Patient Global Impression of Improvement (PGI-I) Scale | 5.26 units on a scale | Standard Deviation 1.04 |
| Reduced Injection Sites (5) | Patient Impression of Clinical Improvement After BTX-A - Patient Global Impression of Improvement (PGI-I) Scale | 4.88 units on a scale | Standard Deviation 1.09 |
p-value: 0.21t-test, 2 sided
Secondary
Patient Reported Procedural Discomfort - Numeric Pain Rating Scale (NPRS)
Participants rated their pain using the NPRS to assess discomfort during the BTX-A procedure. The NPRS is an 11-point scale (0-10), where 0 represents no pain and 10 indicates the worst pain ever experienced. Higher scores reflect greater pain intensity. We report the change in NPRS scores from before to immediately after the procedure.
Time frame: Prior to and immediately after BTX-A injections
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Injection Sites (20) | Patient Reported Procedural Discomfort - Numeric Pain Rating Scale (NPRS) | 3.39 units on a scale | Standard Deviation 3.01 |
| Reduced Injection Sites (5) | Patient Reported Procedural Discomfort - Numeric Pain Rating Scale (NPRS) | 0.57 units on a scale | Standard Deviation 2.07 |
Comparison: Change in post-procedural pain as compared to baselinep-value: <0.00002t-test, 2 sided