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

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

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.

Study Overview

• Status: Terminated
• Conditions: Overactive Bladder
• Intervention / Treatment: Drug: Fesoterodine fumarate; Drug: Placebo; Procedure: Percutaneous Tibial Nerve Stimulation (PTNS)

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic in Arizona (MCSB and MCH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PTNS + fesoterodine fumarate first, then PTNS + placebo; 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; PTNS + 4mg of fesoterodine fumarate for 12 weeks; Other Names: Toviaz; Drug: Placebo; PTNS + placebo for 12 weeks; Procedure: Percutaneous Tibial Nerve Stimulation (PTNS); 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).
Placebo Comparator: PTNS + placebo first, then PTNS + fesoterodine fumarate; 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; PTNS + 4mg of fesoterodine fumarate for 12 weeks; Other Names: Toviaz; Drug: Placebo; PTNS + placebo for 12 weeks; Procedure: Percutaneous Tibial Nerve Stimulation (PTNS); 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Jeffrey Cornella, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: May 3, 2012
• First Submitted That Met QC Criteria: May 21, 2012
• First Posted (Estimate): May 25, 2012

Study Record Updates

• Last Update Posted (Estimate): February 5, 2014
• Last Update Submitted That Met QC Criteria: December 16, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Fesoterodine
• Other Study ID Numbers: 11-004589