Trial of Percutaneous Tibial Nerve Stimulation (PTNS) Versus PTNS and Fesoterodine Fumarate

Study Overview
=================
Brief Summary
-----------------
The investigators are studying two FDA-approved modalities used to treat overactive bladder to determine if they improve overactive bladder with or without urge incontinence when used together rather than separately, percutaneous tibial nerve stimulation (PTNS) versus PTNS and fesoterodine fumarate.

Detailed Description
-----------------
Overactive bladder (OAB) is described as urinary urgency with or without urge incontinence, usually associated with urinary frequency and nocturia. The primary complaint is a strong desire to void without the ability to postpone micturition. Two treatments used in the treatment of OAB are pharmacotherapy and percutaneous tibial nerve stimulation (PTNS). Pharmacotherapy for OAB is based on medications that block the muscarinic receptors of the detrusor muscle. These particular receptors are not unique to the bladder, however, and patients complain of bothersome side effects that are a result of systemic muscarinic receptor blockade. Medications are successful for many patients but compliance is poor and many patients discontinue the medications as a result of side effects, cost, and insufficient symptom improvement. Percutaneous tibial nerve stimulation (PTNS) is a newer treatment modality that provides neuromodulation to the pelvic floor by stimulating the posterior tibial nerve. This nerve is accessed with a fine needle electrode that is inserted in the medial portion of the ankle. This area has long been recognized as having nerve projections to the sacral nerve plexus and can modulate bladder activity. Several studies have clearly demonstrated the effectiveness of neuromodulation to treat urge incontinence. There have been studies comparing the efficacy of pharmacotherapy versus PTNS. In one study, 49% of subjects taking fesoterodine fumarate for urge incontinence reported an improvement in symptoms of overactive bladder. In other studies, 79.5% of patients undergoing PTNS reported improvement or cure. Although studies report similar improvement or cure between the two treatment modalities, there is no evidence of the efficacy of using both PTNS and pharmacotherapy concurrently. This study is aimed at proving synergy between the two treatment modalities when used together in an effort to administer smaller doses of anticholinergic agents, while obtaining comparable or improved urge incontinence.

Official Title
-----------------
Prospective Randomized Trial of Percutaneous Tibial Nerve Stimulation (PTNS) Versus PTNS and Fesoterodine Fumarate

Conditions
-----------------
Overactive Bladder

Intervention / Treatment
-----------------
* Drug: Fesoterodine fumarate
* Drug: Placebo
* Procedure: Percutaneous Tibial Nerve Stimulation (PTNS)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female ages > 18 and < 100 years old without childbearing potential History of overactive bladder with or without urge incontinence) with or without a history of previous anticholinergic use At least 8 voids per 24 hours documented by history and physical and voiding diary Exclusion Criteria: Has had PTNS modulation in the past Has a primary complaint of stress urinary incontinence History of an allergy or sensitivity to tolterodine tartrate tablets or its ingredients History of an allergy or sensitivity to fesoterodine tartrate tablets or its ingredients Has a recent positive urinalysis for infection Has taken anticholinergic medication in the last 4 weeks for overactive bladder Has any of the following: pacemakers or implantable defibrillators excessive bleeding urinary or gastric retention nerve damage and/or neuropathy myasthenia gravis, uncontrolled narrow angle glaucoma liver disease or kidney disease QT prolongation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PTNS + fesoterodine fumarate first, then PTNS + placebo<br>Participants were to be given Percutaneous Tibial Nerve Stimulation (PTNS) + 4mg of fesoterodine fumarate first for 12 weeks, and followed by 4 weeks of washout followed by 12 weeks of PTNS + placebo. | Drug: Fesoterodine fumarate<br>* PTNS + 4mg of fesoterodine fumarate for 12 weeks<br>* Other names: Toviaz;Drug: Placebo<br>* PTNS + placebo for 12 weeks<br>Procedure: Percutaneous Tibial Nerve Stimulation (PTNS)<br>* PTNS is an FDA-approved procedure for the diagnosis of overactive bladder, given on a weekly basis. Participants will be given PTNS + either 4mg of fesoterodine fumarate or placebo for 12 weeks, and followed by 4 weeks of washout followed by 12 weeks of PTNS + the opposite treatment (placebo or fesoterodine fumarate).<br>|
| Placebo Comparator: PTNS + placebo first, then PTNS + fesoterodine fumarate<br>Participants were to be given Percutaneous Tibial Nerve Stimulation (PTNS) + placebo for 12 weeks followed by 4 weeks of washout followed by 12 weeks of PTNS + 4mg of fesoterodine fumarate | Drug: Fesoterodine fumarate<br>* PTNS + 4mg of fesoterodine fumarate for 12 weeks<br>* Other names: Toviaz;Drug: Placebo<br>* PTNS + placebo for 12 weeks<br>Procedure: Percutaneous Tibial Nerve Stimulation (PTNS)<br>* PTNS is an FDA-approved procedure for the diagnosis of overactive bladder, given on a weekly basis. Participants will be given PTNS + either 4mg of fesoterodine fumarate or placebo for 12 weeks, and followed by 4 weeks of washout followed by 12 weeks of PTNS + the opposite treatment (placebo or fesoterodine fumarate).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Urinary Voids Per 24 Hours After 12 Weeks of Therapy |  | From baseline to 12 weeks post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Urinary Urge Incontinence Episodes in 24 Hours |  | Baseline, 12 weeks post treatment | 
| Number of Voids Causing Waking |  | From baseline to 12 weeks post treatment | 
| Volume Voided Per Day |  | From baseline to 12 weeks post treatment | 
| Number of Urgency Episodes Scored by the Indevus Urgency Severity Scale (IUSS) | The IUSS has 4 levels: none, mild, moderate, and severe. An episode characterized as severe according to this scale would qualify as an urgency episode. | baseline, 12 weeks post treatment | 
| Change in Score on Overactive Bladder Questionnaire (QAB-q) | The QAB-q is a self-administered, 33-item questionnaire containing a symptom bother and health related quality of life scale. Each item has a choice of 6 responses, ranging from not at all to a very great deal. Therefore, the total score could range from 33 (no discomfort) to 198 (great discomfort). | Baseline, 12 weeks post treatment |