Clinical trial NCT05463822: Transvaginal Botulinum Toxin A Chemodenervation for Overactive Bladder
Official title: Feasibility and Efficacy of Transvaginal Botulinum Toxin A Chemodenervation of the Bladder for the Third Line Treatment of Refractory Overactive Bladder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Overactive Bladder
Bladder, Overactive
Urge Incontinence
Urgency Urinary
Urinary Frequency/Urgency
Keywords: overactive bladder
bladder chemodenervation
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Society for Urodynamics & Female Urology Foundation
First posted: 2022-07-19
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Overactive bladder (OAB) is a highly prevalent disease process that, when refractory to oral medication therapy, can be effectively managed with injection of botulinum toxin A (BTA) into the detrusor muscle of the bladder. However, the traditional procedure requires a cystoscope inserted into the bladder which can be painful and is associated with a risk of urinary tract infection. The purpose of this study is to determine if transvaginal injection of BTA into the detrusor muscle of the bladder wall is feasible to perform, and efficacious for the treatment of refractory overactive bladder.

Detailed description: PURPOSE OF RESEARCH: Women with overactive bladder are invited to participate in a research study of transvaginal injection of botulinum toxin A (BTA) into the bladder wall for overactive bladder. We hope to learn that this route is easy to perform, well tolerated, and is effective in controlling overactive bladder symptoms. Possible participants in this study are selected because they have overactive bladder symptoms that were refractory to oral therapy, and we believe BTA injection therapy may improve symptoms. This drug is FDA approved for treatment of this disorder via the cystoscopic route of delivery when injected into the wall of the bladder for overactive bladder. In our study we will be injecting BTA into the wall of the bladder by simply inserting a small needle through the anterior vaginal wall to deliver BTA to the bladder wall.

DURATION OF STUDY INVOLVEMENT: This research study is expected to take 120 minutes for the baseline visit at week 0 for transvaginal BTA injection, and then 30 minutes for each of the follow-up visits via telehealth or in-person at 6 and 12 weeks following the procedure. Just as in routine clinical practice for cystoscopic BTA injection, subjects will be eligible for repeat BTA injection when they report less than 50% improvement in symptoms after the 12 week study visit. This will help us understand how long the effect of the BTA lasts, which is typically 3 to 12 months with the traditional cystoscopic route of delivery. A new consent form will be signed at the time of each repeat injection.

INJECTION PROCEDURE AND FOLLOW-UP:

* At the week 0 baseline visit, subjects will urinate into a cup for urinalysis to make sure they do not have a urinary tract infection. Subjects will then undergo post-void residual measurement of how much urine is left in the bladder after they urinate using an non-invasive ultrasound bladder scanner, as is routinely done in office, to make sure they are not retaining urine prior to BTA injection.
* If there is no urinary tract infection and subjects are not in urinary retention, then a routine vaginal exam will be performed to confirm the anatomy of the anterior vaginal wall. The investigator will then use a vaginal ultrasound to measure the dimensions of the bladder and the thickness of the trigone of the bladder prior to injection. The ultrasound is then removed. The ultrasound procedure usually takes less than 15 minutes.
* The investigator will then reconstitute the BTA (Botox® 100 units) with preservative free saline for injection, and then using a very thin 25 gauge needle the BTA will be injected into the bladder in a single needle puncture. The injection procedure unusually takes less than 1 minute and patients usually report just a brief cramp during the injection that resolves within 2 minutes following injection.
* The investigator will then perform a repeat vaginal ultrasound to measure the change in the thickness of the trigone of the bladder after injection. The injection site will be observed for hemostasis and subjects will be given a Kotex pad to keep the betadine from staining the underwear. Subjects may see some spotting on the pad for up to 24 hours after injection. Post-injection precautions and teaching will be provided by the investigator after the procedure.
* After the injection, the investigator will schedule subjects for follow-up visits for 6 and 12 weeks after injection. Follow-up visits will be conducted via telehealth or in-person if subjects are not able to complete a telehealth visit. Subjects will be expected to complete the bladder questionnaires and 3-day bladder diary at baseline and before each of these visits so that the investigator can accurately measure the change in overactive bladder symptoms after BTA injection.
* Just as in routine clinical practice for cystoscopic BTA injection, subjects will be eligible for repeat BTA injection when they report less than 50% improvement in symptoms according to the patient global impression of change (PGIC) scale after the 12 week study visit. This will help us understand how long the effect of the BTA lasts, which is typically 3 to 12 months with the traditional cystoscopic route of delivery. A new consent form will be signed at the time of repeat injection.

Eligibility criteria: Inclusion Criteria:

* Females with overactive bladder
* Females who are considering intradetrusor botulinum toxin A chemodenervation for the treatment of refractory overactive bladder

Exclusion Criteria:

* Overactive bladder caused by neurological condition (i.e. spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, etc.)
* Predominance of stress urinary incontinence as reported by the patient
* Involvement in other studies with potentially overlapping indications or symptoms
* Patients who are unable to undergo a transvaginal ultrasound intervention as a result of anatomic barriers or discomfort will be excluded from enrollment
* Patients known to be pregnant or breastfeeding
* Known allergy to botulinum toxin A injection therapy

Primary outcomes:
measure: Response to the Treatment Benefit Scale (TBS) Questionnaire
timeFrame: at 6 weeks and 12 weeks following baseline injection visit (week 0)
Secondary outcomes:
measure: Change in Voiding Diary Symptoms - number of mean daily urgency episodes
timeFrame: baseline injection visit (week 0) and then at 6 weeks and 12 weeks following intervention
measure: Change in Voiding Diary Symptoms - number of mean daily micturition episodes
timeFrame: baseline injection visit (week 0) and then at 6 weeks and 12 weeks following intervention
measure: Change in Overactive Bladder questionnaire, Short Form
timeFrame: baseline injection visit (week 0) and then at 6 weeks and 12 weeks following intervention
measure: Change in International Consultation on Incontinence Questionnaire - short form
timeFrame: baseline injection visit (week 0) and then at 6 weeks and 12 weeks following intervention
Other outcomes:
measure: Assessment of post void residual
timeFrame: baseline injection visit (week 0) and then at 6 weeks and 12 weeks following intervention
measure: Tolerability of the Procedure using the Procedural Pain Questionnaire
timeFrame: at time of intervention (week 0)
Locations:
city: Stanford
country: United States
facility: Urology Clinic (Stanford University), 1000 Welch Road, Suite 100
state: California
Study officials:
affiliation: Stanford University
name: Amy D. Dobberfuhl, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Syan R, Briggs MA, Olivas JC, Srivastava S, Comiter CV, Dobberfuhl AD. Transvaginal ultrasound guided trigone and bladder injection: A cadaveric feasibility study for a novel route of intradetrusor chemodenervation. Investig Clin Urol. 2019 Jan;60(1):40-45. doi: 10.4111/icu.2019.60.1.40. Epub 2018 Dec 24.
citation: Dobberfuhl AD, van Uem S, Versi E. Trigone as a diagnostic and therapeutic target for bladder-centric interstitial cystitis/bladder pain syndrome. Int Urogynecol J. 2021 Dec;32(12):3105-3111. doi: 10.1007/s00192-021-04878-9. Epub 2021 Jun 22.
citation: Dobberfuhl AD. Pathophysiology, assessment, and treatment of overactive bladder symptoms in patients with interstitial cystitis/bladder pain syndrome. Neurourol Urodyn. 2022 Nov;41(8):1958-1966. doi: 10.1002/nau.24958. Epub 2022 May 24.