Optimization of OnabotulinumtoxinA (BTX-A) Injection for the Treatment of Neurogenic Lower Urinary Tract Dysfunction (BOND)

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.

Study Overview

• Status: Recruiting
• Conditions: Overactive Bladder; Lower Urinary Tract Symptoms; Neurogenic Bladder; Neurogenic Detrusor Overactivity; Neuro: Neurogenic Bladder
• Intervention / Treatment: Procedure: Standard number of injection sites; Procedure: Reduced number of injection sites

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.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Annie Chen, MD; Phone Number: (713) 441-6455; Email: achen@houstonmethodist.org
• Study Contact Backup: Name: Hamida Rajab; Phone Number: (713) 441-6455; Email: hrajab@houstonmethodist.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Hospital
      • Contact: Hamida Rajab; Phone Number: 713-441-6455; Email: hrajab@houstonmethodist.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Injection Sites; Standard number of injections	Procedure: 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.
Experimental: Reduced Injection Sites; Reduced number of injections	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Willingness to repeat procedure visual analog scale	A likert scale to measure the patient's willingness to repeat procedure. 0=Never (worst outcome), 7=Definitely (best outcome)	Immediately after injection, 6 week follow-up after BTX-A injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICIQ-UI SF Questionnaire	International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form standardized survey to measure change in neurogenic bladder symptoms before and after BTX-A. 12=Worst, 0=Best.	Immediately prior to injection, 6 week follow-up after BTX-A injection
NBSS-SF	Neurogenic bladder symptom score-short form standardized survey to measure change in neurogenic bladder symptoms before and after BTX-A. 21=worst score possible, 0=best score possible	Immediately prior to injection, 6 week follow-up after BTX-A injection
PGI score	Patient global impression of improvement after adminstration of BTX-A. 1=Very much worse, 7=Very much better	Immediately after injection, 6 week follow-up after BTX-A injection
Numeric Pain Rating Scale	Patient's rating of pain before and after BTX-A treatment. 0=no pain (best), 10=worst pain of my life (worst outcome)	Immediately prior to injection, immediately after BTX-A injection

Collaborators and Investigators

• Sponsor: The Methodist Hospital Research Institute
• Collaborators: Collaborating for the Advancement of Interdisciplinary Research in Benign Urology
• Investigators: Principal Investigator: Rose Khavari, MD, Houston Methodist Research Group

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: September 22, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Lower urinary tract symptoms; neurogenic bladder; Neurogenic detrusor overactivity; Onabotulinum toxinA
• Additional Relevant MeSH Terms: Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Urological Manifestations; Neurologic Manifestations; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder, Overactive; Lower Urinary Tract Symptoms; Urinary Bladder, Neurogenic
• Other Study ID Numbers: Pro00037721 (Other Identifier: Advarra IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No