Comparison of Combination Therapy vs Single Agent Therapy for Treatment of Urge Incontinence.

Study Overview
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Brief Summary
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This is a randomized double-blind placebo-controlled clinical trial of posterior tibial nerve stimulation (PTNS) plus extended release oxybutynin versus PTNS alone (placebo pills) in women undergoing treatment of urgency urinary incontinence (UUI). The investigators hypothesize that combination therapy with PTNS and anticholinergic medication will result in a significant incremental improvement in UUI symptoms over that achieved with PTNS alone. In addition, the investigators hypothesize that the addition of anticholinergics to PTNS will result in a greater improvement in patients' perception of treatment response, symptom distress, and quality of life than PTNS alone. Specific Aim 1: To compare the change, from baseline, in mean number of UUI episodes per day using a 3-day bladder diary between PTNS plus anticholinergic medication versus PTNS plus placebo in women undergoing treatment for UUI. Specific Aim 2: To compare the change, from baseline, in a 24hr pad weight between PTNS plus anticholinergic medication versus PTNS plus placebo. Specific Aim 3: To compare subjective treatment response, symptoms distress, and quality of life between PTNS plus anticholinergic medication versus PTNS plus placebo utilizing the Patient Global Impression of Improvement (PGI-I) and the Overactive Bladder Questionnaire Short Form (OABq-SF). An interim analysis will be conducted by an independent entity after 50 participants have completed the study protocol. A Data Safety Monitoring Board is not utilized because the study utilizes FDA approved treatments for urgency urinary incontinence.

Official Title
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Double-Blind Randomized Controlled Trial of Extended Release Oxybutynin Versus Placebo in Women Receiving Posterior Tibial Nerve Stimulation for Treatment of Urgency Urinary Incontinence

Conditions
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Urinary Urge Incontinence

Intervention / Treatment
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* Drug: Oxybutynin extended release
* Device: Posterior Tibial Nerve Stimulation
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients > 18 years of age > 3 UUI episodes on a 3-day bladder diary Urge predominant ( > 50% of total incontinence episodes) urinary incontinence based on a three-day bladder diary Existing insurance coverage of PTNS therapy. Ability to undergo weekly PTNS treatments in clinic for 6 week period of time and complete all study related items Not on an anticholinergic or beta agonist medication or, if they are, willing to undergone a three week washout period prior to randomization Exclusion Criteria: Any previous PTNS therapy, intra-detrusor botulinum toxin injections, or implanted sacral neuromodulation Contraindication to anticholinergic therapy (narrow-angle glaucoma or gastric retention) or PTNS therapy (implanted pacemaker/defibrillator or peripheral neuropathy) Symptomatic urinary tract infection that has not resolved prior to randomization Surgical treatment for stress urinary incontinence or pelvic organ prolapse recommended or planned at time of enrollment Surgically altered detrusor muscle Known diagnosis or history of neurogenic bladder, post void residual volume >150ml, bladder malignancy, interstitial cystitis/painful bladder syndrome, or pelvic radiation Surgery for pelvic organ prolapse or stress urinary incontinence within the previous 3 months Pregnancy, lactation, or planned pregnancy during study period

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oxybutynin plus PTNS<br>Oxybutynin extended release (blinded tablet) 5mg by mouth daily for 6 weeks, Posterior Tibial Nerve Stimulation utilizing the Urgent PC neuromodulation system administered weekly in the office setting for a total of 6 weeks. | Drug: Oxybutynin extended release<br>* 5mg tablet taken by mouth daily for 6 weeks<br>* Other names: Ditropan XL;Device: Posterior Tibial Nerve Stimulation<br>* In office therapy administered for 30 minutes once every week for a total of 6 weeks<br>* Other names: Urgent PC Neuromodulation system;|
| Placebo Comparator: Placebo plus PTNS<br>Placebo (blinded tablet) taken daily for 6 weeks. Posterior Tibial Nerve Stimulation utilizing the Urgent PC neuromodulation system administered weekly in the office setting for a total of 6 weeks. | Device: Posterior Tibial Nerve Stimulation<br>* In office therapy administered for 30 minutes once every week for a total of 6 weeks<br>* Other names: Urgent PC Neuromodulation system;Drug: Placebo<br>* Tablet taken by mouth daily for 6 weeks<br>* Other names: Dextrose powder;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Median Number of UUI Episodes Per Day | To compare the change, from baseline, in median number of UUI episodes per day using a 3-day bladder diary between PTNS plus anticholinergic medication versus PTNS plus placebo in women undergoing treatment for UUI. UUI change score will be calculated [post-treatment UUI/day minus pre-treatment UUI/day]. | Baseline, 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24hr Pad Weight | To compare the change, from baseline, in 24h pad weight between PTNS plus anticholinergic medication versus PTNS plus placebo. Change in median 24h pad weight from baseline to 6 weeks was compared between the 2 groups using Wilcoxon Rank Sum test. | Baseline, 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Posterior Tibial Nerve Stimulation, Urinary Urge Incontinence, PTNS, Neuromodulation, Oxybutynin, Anticholinergic Medication