Refractory Urge Incontinence and Botox Injections

Study Overview
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Brief Summary
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The purpose of this study is to see whether Botox A (injected into the bladder muscle) can improve symptoms of urge incontinence that has not improved with usual medical treatments.

Detailed Description
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Women who suffer with urge incontinence may not get relief with usual medical treatment (such as medications or behavioral techniques). We plan to enroll women with refractory urge incontinence in centers across the US. Study participants will undergo cystoscopy (telescope look into the bladder) and injection of either Botox A or placebo. If symptoms are not adequately relieved, subjects participants will receive a second injection that is Botox A. Participants are interviewed monthly by study personnel to determine symptoms and health status.

Official Title
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Refractory Urge Incontinence and Botox Injections

Conditions
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Urinary Incontinence, Detrusor Overactivity, Urinary Urgency, Urge Urinary Incontinence

Intervention / Treatment
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* Drug: Botulinum Toxin A, bladder detrusor muscle injection
* Drug: Vehicle saline as placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult women Detrusor overactivity incontinence confirmed by urodynamic testing Symptoms refractory to standard first- and second-line treatments 6 or more urge incontinence episodes on 3-day bladder diary Normal neurological examination Exclusion Criteria: Urinary retention Allergy to Botox (Botulinum Toxin A) Previous bladder treatment with Botox (Botulinum Toxin A) in the past year Pregnancy or planning pregnancy within next year Neurologic disease with impaired neurotransmission

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botox A<br>up to two injections of 200 Units of intra-detrusor Botulinum Toxin A , which must be separated by at least eight weeks and no more than 52 weeks | Drug: Botulinum Toxin A, bladder detrusor muscle injection<br>* 200 U provided as a total of 6 cc of the masked substance into approximately 15 to 20 different detrusor muscle sites under direct visualization. Injections will be spread out to equally cover the entire dome of the bladder, but spare the bladder trigone and ureteral orifices.<br>* Other names: Botox;|
| Placebo Comparator: Placebo<br>up to two injections of inactive injection (carrier saline), which must be separated by at least eight weeks and no more than 52 weeks | Drug: Vehicle saline as placebo<br>* A total of 6 cc of the masked substance into approximately 15 to 20 different detrusor muscle sites under direct visualization. Injections will be spread out to equally cover the entire dome of the bladder, but spare the bladder trigone and ureteral orifices<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recurrence of detrusor overactivity incontinence symptoms | To allow sufficient time for the onset of action of botulinum toxin A, the earliest outcome measurement was 60 days after injection. Failure was defined as a patient global impression of improvement (PGI-I) score of 4 or greater, the commencement of any new treatment at any time after the first injection or increased intensity of previously established treatment for DOI. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in incontinence episode frequency by bladder diary | based on the 3-day bladder diary completed pre-intervention and at 4 weeks post injection. A successful within-subject outcome will be defined as >75% reduction in the frequency of urge incontinence episodes compared to the baseline frequency. | At 12 mos after first injection., but no less than 1 mo after second injection | 
| Incontinence-related and health-related quality of life | measured by the Urinary Distress Inventory subscale of the PFDI/PFIQ, the PISQ, and SF-36 administered at 4 weeks after the initial injection and either prior to any re-treatment or at the completion of study participation, whichever is earlier. | At 12 mos after first injection, but no less than 1 mo after second injection. | 
| Voiding dysfunction requiring catheterization |  | throughout 12-month study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Botulinum Toxin A, Urinary Incontinence, Detrusor Overactivity