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

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

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.

Study Overview

• Status: Terminated
• Conditions: Urinary Urge Incontinence
• Intervention / Treatment: Drug: Oxybutynin extended release; Device: Posterior Tibial Nerve Stimulation; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27707
      • Duke Urogynecology
    • Raleigh, North Carolina, United States, 27607
      • Duke OB/GYN Consultants of Raleigh

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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxybutynin plus PTNS; 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; 5mg tablet taken by mouth daily for 6 weeks; Other Names: Ditropan XL; Device: Posterior Tibial Nerve Stimulation; In office therapy administered for 30 minutes once every week for a total of 6 weeks; Other Names: Urgent PC Neuromodulation system
Placebo Comparator: Placebo plus PTNS; 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; In office therapy administered for 30 minutes once every week for a total of 6 weeks; Other Names: Urgent PC Neuromodulation system; Drug: Placebo; Tablet taken by mouth daily for 6 weeks; Other Names: Dextrose powder

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Patient Global Impression of Improvement (PGI-I)	The Patient Global Impression of Improvement (PGI-I) is a transition scale that is a single question asking the patient to rate their urinary tract condition now, as compared with how it was prior to before beginning treatment on a scale from 1 (Very much better to) 7 (Very much worse).	Baseline, 6 weeks
Change in the Overactive Bladder Questionnaire Short Form (OABq-SF) Part 1	Part 1 of the OABq-SF questionnaire asks about the relative bother a patient experiences with regard to overactive bladder symptoms over the previous 4 weeks. This part of the questionnaire has 6 questions, with scores ranging from 6 (least amount of bother) to 36 (most amount of bother). For this secondary outcome, we are measuring the change in score on the OABq-SF Part 1 from baseline to 6 weeks. Median change in scores were compared between the 2 groups using Wilcoxon Rank Sum test.	Baseline, 6 weeks
Change in the Overactive Bladder Questionnaire Short Form (OABq-SF) Part 2	Part 2 of the OABq-SF questionnaire asks about the relative bother a patient experiences with regard to overactive bladder symptoms over the previous 4 weeks. This part of the questionnaire has 13 questions, with scores ranging from 13 (least amount of bother) to 78 (most amount of bother). For this secondary outcome, we are measuring the change in score on the OABq-SF Part 2 from baseline to 6 weeks. Median change in scores were compared between the 2 groups using Wilcoxon Rank Sum test.	Baseline, 6 weeks
Change in the Urinary Distress Inventory (UDI-6)	The UDI-6 is a 6-question inventory of how frequently and how much bother patients have from overactive bladder symptoms. The scores range from 0 (not at all) to 24 (a great deal of bother). We compared the change in scores from baseline to 6 weeks between the 2 groups using Wilcoxon Rank Sum test.	Baseline, 6 weeks
Change in the Incontinence Impact Questionnaire (IIQ-7)	The IIQ-7 is a 7-question score assessing how urinary incontinence affects a patient's various activities and feelings. The range of possible scores is from 0 (not at all) to 28 (a great deal). Median change in scores from baseline to 6 weeks were compared between the 2 groups using Wilcoxon Rank Sum test.	Baseline, 6 weeks
Change in Treatment Satisfaction Questionnaire for Medication, Version Two (TSQMvII) - Global Satisfaction Domain	To compare treatment satisfaction between PTNS plus anticholinergic medication versus PTNS plus placebo using the Treatment Satisfaction Questionnaire for Medication, version two (TSQMvII). Patients completed the questionnaire at baseline and again at 6 weeks. The TSQMvII satisfaction domains at each timepjoint were transformed into a score from 0 (extremely dissatisfied) to 100 (extremely satisfied). Median change in scores from baseline to 6 weeks were compared between the 2 groups using Wilcoxon Rank Sum Test.	Baseline, 6 weeks
Change in Treatment Satisfaction Questionnaire for Medication, Version Two (TSQMvII) - Side Effects Domain	To compare bother from medication side effects between PTNS plus anticholinergic medication versus PTNS plus placebo using the Treatment Satisfaction Questionnaire for Medication, version two (TSQMvII). The questionnaire was completed at baseline and at 6 weeks. The TSQMvII side effects domain at each time point was transformed into a score from 0 (extremely dissatisfied) to 150 (extremely satisfied). Median change in scores from baseline to 6 weeks were compared between the 2 groups using Wilcoxon Rank Sum Test.	Baseline, 6 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Society of Urodynamics and Female Pelvic Medicine & Urogenital Reconstruction
• Investigators: Principal Investigator: Nazema Y Siddiqui, MD, MHS, Duke University

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): November 21, 2016
• Study Completion (Actual): November 21, 2016

Study Registration Dates

• First Submitted: June 25, 2014
• First Submitted That Met QC Criteria: June 25, 2014
• First Posted (Estimate): June 27, 2014

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: December 28, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Neuromodulation; PTNS; Urinary Urge Incontinence; Oxybutynin; Posterior Tibial Nerve Stimulation; Anticholinergic Medication
• Additional Relevant MeSH Terms: Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Urinary Incontinence; Urinary Incontinence, Urge; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Oxybutynin
• Other Study ID Numbers: Pro00052742