Transvaginal Botulinum Toxin A Chemodenervation for Overactive Bladder

NCT ID: NCT05463822

Last Updated: 2022-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-20
• Study Completion Date: 2021-09-27

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.

Conditions

Overactive Bladder; Bladder, Overactive; Urge Incontinence; Urgency Urinary; Urinary Frequency/Urgency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Transvaginal botulinum toxin A (BTA) injection

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Botox® 100 units

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Society for Urodynamics & Female Urology Foundation

UNKNOWN

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Amy Diane Dobberfuhl

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amy D. Dobberfuhl, M.D.

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Urology Clinic (Stanford University), 1000 Welch Road, Suite 100

Stanford, California, United States

Countries

United States

References

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Reference Type: BACKGROUND

PMID: 26433883 (View on PubMed)

Gormley EA, Lightner DJ, Burgio KL, Chai TC, Clemens JQ, Culkin DJ, Das AK, Foster HE Jr, Scarpero HM, Tessier CD, Vasavada SP; American Urological Association; Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol. 2012 Dec;188(6 Suppl):2455-63. doi: 10.1016/j.juro.2012.09.079. Epub 2012 Oct 24.

Reference Type: BACKGROUND

PMID: 23098785 (View on PubMed)

Nitti VW, Dmochowski R, Herschorn S, Sand P, Thompson C, Nardo C, Yan X, Haag-Molkenteller C; EMBARK Study Group. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol. 2013 Jun;189(6):2186-93. doi: 10.1016/j.juro.2012.12.022. Epub 2012 Dec 14.

Reference Type: BACKGROUND

PMID: 23246476 (View on PubMed)

Abdel-Meguid TA. Botulinum toxin-A injections into neurogenic overactive bladder--to include or exclude the trigone? A prospective, randomized, controlled trial. J Urol. 2010 Dec;184(6):2423-8. doi: 10.1016/j.juro.2010.08.028. Epub 2010 Oct 16.

Reference Type: BACKGROUND

PMID: 20952003 (View on PubMed)

Kuo HC. Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics. Neurourol Urodyn. 2011 Sep;30(7):1242-8. doi: 10.1002/nau.21054. Epub 2011 May 10.

Reference Type: BACKGROUND

PMID: 21560152 (View on PubMed)

Lucioni A, Rapp DE, Gong EM, Fedunok P, Bales GT. Intravesical botulinum type A toxin injection in patients with overactive bladder: Trigone versus trigone-sparing injection. Can J Urol. 2006 Oct;13(5):3291-5.

Reference Type: BACKGROUND

PMID: 17076955 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30637360 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34156506 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35607890 (View on PubMed)

Other Identifiers

SPO # 133508

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IRB-44813

Identifier Type: -

Identifier Source: org_study_id