FETOC: Transvaginal Botulinum Toxin A Chemodenervation for Overactive Bladder

Sponsor

Stanford University (Other)

Overall Status

Completed

CT.gov ID

NCT05463822

Collaborator

Society for Urodynamics & Female Urology Foundation (Other)

Enrollment

Location

Arm

27.3

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Overactive Bladder Bladder, Overactive Urge Incontinence Urgency Urinary Urinary Frequency/Urgency	Drug: Transvaginal botulinum toxin A (BTA) injection	Early Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Feasibility and Efficacy of Transvaginal Botulinum Toxin A Chemodenervation of the Bladder for the Third Line Treatment of Refractory Overactive Bladder

Actual Study Start Date :

Jun 20, 2019

Actual Primary Completion Date :

Sep 27, 2021

Actual Study Completion Date :

Sep 27, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Transvaginal botulinum toxin A (BTA) injection Botulinum toxin A (Botox® 100 units) will be injected into the detrusor muscle of the bladder by inserting a needle through the anterior vaginal wall.	Drug: Transvaginal botulinum toxin A (BTA) injection Botulinum toxin A (Botox® 100 units) will be injected into the detrusor muscle of the bladder by inserting a needle through the anterior vaginal wall. Other Names: Botox® 100 units

Arm

Intervention/Treatment

Experimental: Transvaginal botulinum toxin A (BTA) injection

Botulinum toxin A (Botox® 100 units) will be injected into the detrusor muscle of the bladder by inserting a needle through the anterior vaginal wall.

Drug: Transvaginal botulinum toxin A (BTA) injection

Botulinum toxin A (Botox® 100 units) will be injected into the detrusor muscle of the bladder by inserting a needle through the anterior vaginal wall.

Other Names:

Botox® 100 units

Outcome Measures

Primary Outcome Measures

Response to the Treatment Benefit Scale (TBS) Questionnaire [at 6 weeks and 12 weeks following baseline injection visit (week 0)]
Assessing improvement in urinary symptoms following intervention. The Treatment Benefit Scale Questionnaire asks patients to state if their condition (overactive bladder) has 1) greatly improved, 2) improved, 3) not changed, or 4) worsened during treatment. Patients who select 1 or 2 are considered to have derived a perceived benefit from the treatment, and will represent those patients who had a positive TBS response.

Secondary Outcome Measures

Change in Voiding Diary Symptoms - number of mean daily urgency episodes [baseline injection visit (week 0) and then at 6 weeks and 12 weeks following intervention]
Assessing the mean change in number of urgency episodes recorded in a three day Voiding Diary. A higher number implies worse urinary symptoms. Efficacy of treatment is associated with a 50% reduction in urgency episodes daily
Change in Voiding Diary Symptoms - number of mean daily micturition episodes [baseline injection visit (week 0) and then at 6 weeks and 12 weeks following intervention]
Assessing the mean change in number of micturition episodes recorded in a three day Voiding Diary. A higher number implies worse urinary symptoms. Efficacy of treatment is associated with a 50% reduction in micturition episodes daily
Change in Overactive Bladder questionnaire, Short Form [baseline injection visit (week 0) and then at 6 weeks and 12 weeks following intervention]
Assessing changes in Overactive Bladder questionnaire, Short Form (OABq-SF, a validated questionnaire evaluating lower urinary tract symptoms) following intervention. This questionnaire is composed of 6 questions asking patients, "during the past 4 weeks, how bothered were you by..." 1. an uncomfortable urge to urinate? 2. A sudden urge to urinate with little or no warning? 3. Accidental loss of small amounts of urine? 4. nighttime urination? 5. Waking up at night because you had to urinate? 6. Urine loss associated with a strong desire to urinate? For each question, patients select 1) not at all, 2) a little bit, 3) somewhat, 4) quite a bit, 5) a great deal, 6) a very great deal. Total scores range from a score of 6 - 36. A higher score implies worse urinary symptoms. A reduction of the overall score by 50% will be considered a treatment benefit.
Change in International Consultation on Incontinence Questionnaire - short form [baseline injection visit (week 0) and then at 6 weeks and 12 weeks following intervention]
Assessing changes in International Consultation on Incontinence Questionnaire - short form (ICIQ-SF, a validated questionnaire evaluating lower urinary tract symptoms) following intervention. This questionnaire asks 3 questions on urinary symptoms: 1) How often do you leak? to which patients respond 0-never, 1-about once a week or less often, 2-two or three times a week, 3-about once a day, 4-several times a day, 5-all the time. 2) how much urine do you usually leak? to which patients respond 0-none, 2-a small amount, 4-a moderate amount, 6-a large amount. 3) Overall, how much does leaking urine interfere with your everyday life? patients select a score from 0-10, where 0 is not at all, and 10 is a great deal. The sum of these questions composes the overall ICIQ score. A higher score implies worse urinary symptoms. A reduction of the overall score by 50% will be considered a treatment benefit.

Other Outcome Measures

Assessment of post void residual [baseline injection visit (week 0) and then at 6 weeks and 12 weeks following intervention]
Assessing post void residuals of patients following therapy at follow up appointments using ultrasound, routinely performed in a Urology practice on initial and follow up visits
Tolerability of the Procedure using the Procedural Pain Questionnaire [at time of intervention (week 0)]
This is a qualitative questionnaire. The first question asks patient to select how uncomfortable the procedure was, from 0-10, where 0 is no pain and 10 is maximum pain. A higher score implies worse discomfort, and will be measured across all patients. Question 2 asks which part of the procedure was most uncomfortable: initial entry, during injection of medication, and not relevant. Question 3 asks if the procedure had to be terminated early due to discomfort. Score of "yes" indicate poor tolerability. Question 4 asks if patients would be willing to undergo the procedure again if beneficial. Answers of "no" indicate poor tolerability. Responses to each question will be collected and will together indicate if the procedure was well tolerated or not.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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