Clinical trial NCT06796855: Comparing Treatments for Refractory Overactive Bladder: Bladder Denervation vs Botulinum Toxin Injections
Official title: Selective Bladder Denervation vs Intramuscular Onabotulinum Toxin A for Refractory Overactive Bladder: A Randomized Comparative Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Overactive Bladder Syndrome
Refractory Overactive Bladder
Keywords: Onabotulinum Toxin A
Selective Bladder Denervation
RF Ablation
Overactive Bladder
Intravesical Botox
Lead sponsor: Bagcilar Training and Research Hospital
Sponsor class: OTHER_GOV
First posted: 2025-01-28
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study uses a parallel design, where participants are randomly assigned to one of two groups for the duration of the study. The two groups are:

The Selective Bladder Denervation group, which undergoes treatment with radiofrequency ablation (RFA).

The Intravesical Onabotulinum Toxin A group, which receives onabotulinum toxin A injections into the bladder wall.

Each group receives its respective intervention without crossover between treatments. Randomization was performed using the "Research Randomizer" tool to ensure an unbiased allocation of participants.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare the effectiveness and safety of two treatments for refractory overactive bladder in adult women.

The main questions it aims to answer are:

* Does selective bladder denervation using radiofrequency ablation improve overactive bladder symptoms more effectively than intravesical Onabotulinum toxin A injections?
* What are the safety profiles of each treatment?

Researchers will compare selective bladder denervation using radiofrequency ablation to intravesical Onabotulinum toxin A injections to determine which treatment is more effective and tolerable for patients whose symptoms persist despite behavioral and medical therapies.

Participants will:

* Be women aged 18 and older diagnosed with overactive bladder who did not benefit from at least two prior medical treatments for 3 months or were unable to tolerate those treatments.
* Be randomly assigned to receive either radiofrequency ablation or Onabotulinum toxin A treatment.
* Attend follow-up visits at weeks 2, 4, and 12 over a 3-month period, during which symptom improvement will be assessed using validated questionnaires and side effects will be monitored through imaging, blood, and urine tests.

Detailed description: This randomized clinical trial aims to evaluate the effectiveness and safety of two third-line treatment options for women with refractory overactive bladder syndrome: selective bladder denervation using radiofrequency ablation and intravesical Onabotulinum toxin A injection.

The study includes 60 symptomatic female patients aged 18 years and older who met the eligibility criteria and had either failed to achieve adequate symptom control with at least two different oral pharmacological treatments or were unable to tolerate such therapies. Participants were randomly assigned into two equal groups, with 30 patients in each group, using the "Research Randomizer" tool.

Participant Assessments:

At the initial assessment, all participants underwent the following evaluations:

* A detailed medical history, including past surgeries and prior medication use.
* Urinary tests, including urinalysis and urine culture, as well as blood biochemical evaluations.
* Imaging with urinary system ultrasonography to evaluate both the upper and lower urinary tract and measure post-void residual urine volume.
* Symptom assessment using the following validated patient-reported outcome questionnaires:

International Consultation on Incontinence Questionnaire - Female Lower Urinary Tract Symptoms (ICIQ-FLUTS).

Overactive Bladder Symptom Score Questionnaire (OAB-V8). Incontinence Quality of Life Questionnaire (I-QOL).

Additionally, participants were asked to maintain a three-day bladder diary to document:

* The number of daily urinations.
* Episodes of waking up at night to urinate (nocturia).
* Urgency episodes.
* Instances of urge urinary incontinence.

Treatment Groups:

1. Selective Bladder Denervation with Radiofrequency Ablation:

   This procedure was performed under general anesthesia using the Apro Korea AK-F200 radiofrequency system, which operates with temperature and impedance control along with a cooling mechanism.

   Radiofrequency energy was applied to four specific submucosal points in the bladder's trigone region.

   The target tissue temperature was 100 degrees Celsius, with energy delivery set to 25 watts for 60 seconds at each point.

   Post-procedure imaging and post-void residual urine measurements were performed to ensure patient safety.
2. Intravesical Onabotulinum Toxin A Injection:

This treatment was administered under local anesthesia using a rigid cystoscope.

A total dose of 100 units of Onabotulinum toxin A was injected into ten separate points across the bladder wall.

Follow-Up Protocol:

Patients were scheduled for follow-up visits at 2, 4, and 12 weeks after the intervention. At each visit, the following evaluations were conducted:

* Ultrasonographic imaging of the urinary system to assess for any upper tract dilation (hydronephrosis) and to measure post-void residual urine volume.
* Laboratory assessments, including urinalysis and serum creatinine level evaluation.
* Reassessment of urinary symptoms through a repeat three-day bladder diary and completion of the same validated patient-reported outcome questionnaires.

Study Objective:

This clinical trial aims to compare the two treatment modalities concerning their effectiveness in relieving symptoms of overactive bladder, improving patients' quality of life, and assessing their safety profiles. The results of this study are expected to provide valuable insights into the optimal third-line treatment approach for patients with refractory overactive bladder who have not responded to conventional behavioral and pharmacological therapies.

Eligibility criteria: Inclusion Criteria:

Biological females aged 18 years or older.

Diagnosis of refractory overactive bladder syndrome, defined as:

* Persistent symptoms despite having completed behavioral therapy and at least two different oral pharmacotherapies (e.g., anticholinergics or beta-3 adrenergic agonists) for a minimum of 3 months each; or
* Inability to tolerate oral pharmacotherapy for overactive bladder syndrome. Willingness and ability to provide written informed consent. Ability to comply with the study protocol, including attendance at scheduled follow-up visits and completion of validated symptom assessment questionnaires (e.g., Overactive Bladder Symptom Score - OAB-V8, International Consultation on Incontinence Questionnaire - Female Lower Urinary Tract Symptoms - ICIQ-FLUTS).

Exclusion Criteria:

Pregnancy or intention to become pregnant within 12 months of enrollment. History of stress urinary incontinence as the predominant symptom.

Recent interventions prior to enrollment:

* Oral medication for overactive bladder within the past 2 weeks.
* Intravesical Onabotulinum toxin A injection within the past 9 months.
* Pelvic electrical stimulation within the past 2 weeks. Active or chronic urinary tract infection or a history of urinary retention within the past 6 months.

Active hematuria or known bleeding disorders.

History or current diagnosis of:

* Bladder cancer or ongoing bladder cancer treatment.
* Bladder outlet obstruction, ureteral dysfunction, ureteral stricture, or vesicoureteral reflux.
* Elevated serum creatinine level (≥2 times the upper limit of normal) within the past 6 months.

Neurological conditions affecting bladder function, including but not limited to:

* Multiple sclerosis.
* Myasthenia gravis.
* Spinal cord injury or disease. Any condition deemed by the investigator to interfere with study participation or accurate evaluation of outcomes.

Primary outcomes:
measure: Change from Baseline in Overactive Bladder Assessment Tool (OAB-V8) Total Score at 12 Weeks
timeFrame: From baseline to 12 weeks post-treatment
Secondary outcomes:
measure: Change from Baseline in International Consultation on Incontinence Questionnaire - Female Lower Urinary Tract Symptoms (ICQ-FLUTS) Score at 12 Weeks
timeFrame: From baseline to 12 weeks post-treatment
measure: Change from Baseline in Incontinence Quality of Life (I-QOL) Score at 12 Weeks
timeFrame: From baseline to 12 weeks post-treatment
measure: Change from Baseline in Urgency and Urgency Urinary Incontinence (UUI) Episodes at 12 Weeks
timeFrame: From baseline to 12 weeks post-treatment
measure: Incidence of Treatment-Related Adverse Events at 12 Weeks
timeFrame: From baseline to 12 weeks post-treatment
Other outcomes:
measure: Change from Baseline in Daily Voiding Frequency and Nocturia Episodes at 12 Weeks
timeFrame: From baseline to 12 weeks post-treatment
measure: Change from Baseline in Post-Void Residual (PVR) Urine Volume at 12 Weeks
timeFrame: From baseline to 12 weeks post-treatment
measure: Incidence of Culture-Proven Urinary Tract Infections (UTIs) at 12 Weeks
timeFrame: From baseline to 12 weeks post-treatment
Locations:
city: Istanbul
country: Turkey
facility: University of Health Sciences, Istanbul Bagcilar Hospital
Study officials:
affiliation: University of Health Sciences, Istanbul Bagcilar Hospital
name: Muhammet M Dinçer, MD
role: STUDY_DIRECTOR
References:
citation: Rovner ES, Versi E, Le Mai T, Dmochowski RR, De Wachter S. One-year results with selective bladder denervation in women with refractory overactive bladder. Neurourol Urodyn. 2019 Nov;38(8):2178-2184. doi: 10.1002/nau.24110. Epub 2019 Jul 29.
citation: Fugett J 2nd, Phillips L, Tobin E, Whitbrook E, Bennett H, Shrout J, Coad JE. Selective bladder denervation for overactive bladder (OAB) syndrome: From concept to healing outcomes using the ovine model. Neurourol Urodyn. 2018 Sep;37(7):2097-2105. doi: 10.1002/nau.23560. Epub 2018 Mar 31.
citation: Tu LM, De Wachter S, Robert M, Dmochowski RR, Miller LE, Everaert K. Initial clinical experience with selective bladder denervation for refractory overactive bladder. Neurourol Urodyn. 2019 Feb;38(2):644-652. doi: 10.1002/nau.23881. Epub 2018 Nov 29.