Urinary Urge Incontinence
Conditions
Keywords
Urinary Urge Incontinence, Posterior Tibial Nerve Stimulation, PTNS, Neuromodulation, Oxybutynin, Anticholinergic Medication
Brief summary
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.
Interventions
DRUGOxybutynin extended release
5mg tablet taken by mouth daily for 6 weeks
In office therapy administered for 30 minutes once every week for a total of 6 weeks
DRUGPlacebo
Tablet taken by mouth daily for 6 weeks
Sponsors
Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Median Number of UUI Episodes Per Day | Baseline, 6 weeks | 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 \[post-treatment UUI/day minus pre-treatment UUI/day\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24hr Pad Weight | Baseline, 6 weeks | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in the Overactive Bladder Questionnaire Short Form (OABq-SF) Part 2 | Baseline, 6 weeks | 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. |
| Change in the Urinary Distress Inventory (UDI-6) | Baseline, 6 weeks | 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. |
| Change in the Patient Global Impression of Improvement (PGI-I) | Baseline, 6 weeks | 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). |
| Change in Treatment Satisfaction Questionnaire for Medication, Version Two (TSQMvII) - Global Satisfaction Domain | Baseline, 6 weeks | 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. |
| Change in Treatment Satisfaction Questionnaire for Medication, Version Two (TSQMvII) - Side Effects Domain | Baseline, 6 weeks | 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. |
| Change in the Incontinence Impact Questionnaire (IIQ-7) | Baseline, 6 weeks | 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. |
| Change in the Overactive Bladder Questionnaire Short Form (OABq-SF) Part 1 | Baseline, 6 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Potential participants were identified, recruited, and enrolled at the time of their outpatient clinic visits with the Duke Urogynecology clinic. All women who were considering therapy with posterior tibial nerve stimulation were approached for participation in the study.
Pre-assignment details
A total of 104 patients were assessed for eligibility. Forty-nine patients declined or were deemed ineligible. Fifty-five patients consented to participate but 20 dropped out before randomization. Therefore, a total of 35 patients were randomized as noted in the boxes below (18 in the active medication group, 17 in the placebo group).
Participants by arm
| Arm | Count |
|---|---|
| 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.
Oxybutynin extended release: 5mg tablet taken by mouth daily for 6 weeks
Posterior Tibial Nerve Stimulation: In office therapy administered for 30 minutes once every week for a total of 6 weeks | 18 |
| 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.
Posterior Tibial Nerve Stimulation: In office therapy administered for 30 minutes once every week for a total of 6 weeks
Placebo: Tablet taken by mouth daily for 6 weeks | 16 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Oxybutynin Plus PTNS | Total | Placebo Plus PTNS |
|---|---|---|---|
| Age, Continuous | 72.7 years STANDARD_DEVIATION 9.8 | 71.6 years STANDARD_DEVIATION 9.2 | 70.4 years STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 34 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 28 Participants | 13 Participants |
| Region of Enrollment United States | 18 Participants | 34 Participants | 16 Participants |
| Sex: Female, Male Female | 18 Participants | 34 Participants | 16 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 16 |
| other Total, other adverse events | 0 / 18 | 3 / 16 |
| serious Total, serious adverse events | 0 / 18 | 0 / 16 |
Outcome results
Primary
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 \[post-treatment UUI/day minus pre-treatment UUI/day\].
Time frame: Baseline, 6 weeks
Population: 3 patients in each group did not provide bladder diaries at their 6 week visit, so did not have information available to calculate the primary outcome measure. Median change in UUI episodes/day from baseline to 6 weeks was compared between 2 groups using Wilcoxon Rank Sum test.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxybutynin Plus PTNS | Change in Median Number of UUI Episodes Per Day | -0.3 Urge urinary incontinence episodes/day |
| Placebo Plus PTNS | Change in Median Number of UUI Episodes Per Day | 0.3 Urge urinary incontinence episodes/day |
p-value: 0.2Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline, 6 weeks
Population: Six participants in the placebo+PNTS group and 3 patients in the oxybutynin+PTNS group did not provide a pad weight at the end of the study, and thus were unable to have the pad weight change score calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxybutynin Plus PTNS | Change in 24hr Pad Weight | -52 grams |
| Placebo Plus PTNS | Change in 24hr Pad Weight | -8 grams |
p-value: 0.4Wilcoxon (Mann-Whitney)
Other Pre-specified
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.
Time frame: Baseline, 6 weeks
Population: 1 patient in the oxybutynin+PTNS group did not complete the 6 week IIQ-7 questionnaire so was not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxybutynin Plus PTNS | Change in the Incontinence Impact Questionnaire (IIQ-7) | -9.5 units on a scale |
| Placebo Plus PTNS | Change in the Incontinence Impact Questionnaire (IIQ-7) | -2.4 units on a scale |
p-value: 0.44Wilcoxon (Mann-Whitney)
Other Pre-specified
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.
Time frame: Baseline, 6 weeks
Population: 3 patients in the oxybutynin+PTNS group did not submit their OABq-SF at the end of the study, so they were unable to be included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxybutynin Plus PTNS | Change in the Overactive Bladder Questionnaire Short Form (OABq-SF) Part 1 | -13.3 units on a scale |
| Placebo Plus PTNS | Change in the Overactive Bladder Questionnaire Short Form (OABq-SF) Part 1 | -10 units on a scale |
p-value: 0.26Wilcoxon (Mann-Whitney)
Other Pre-specified
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.
Time frame: Baseline, 6 weeks
Population: Four patients in the oxybutynin+PTNS group and 1 patient in the placebo+PTNS did not submit their OABq-SF part 2 at the end of the study, so they were unable to be included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxybutynin Plus PTNS | Change in the Overactive Bladder Questionnaire Short Form (OABq-SF) Part 2 | 9.2 units on a scale |
| Placebo Plus PTNS | Change in the Overactive Bladder Questionnaire Short Form (OABq-SF) Part 2 | 0 units on a scale |
p-value: 0.06Wilcoxon (Mann-Whitney)
Other Pre-specified
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).
Time frame: Baseline, 6 weeks
Population: 2 patients in the oxybutynin+PTNS group and one patient in the placebo+PTNS group did not complete the 6 week PGI-I questionnaire so they were not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxybutynin Plus PTNS | Change in the Patient Global Impression of Improvement (PGI-I) | -1 units on a scale |
| Placebo Plus PTNS | Change in the Patient Global Impression of Improvement (PGI-I) | -1 units on a scale |
p-value: 0.48Wilcoxon (Mann-Whitney)
Other Pre-specified
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.
Time frame: Baseline, 6 weeks
Population: 1 patient in the oxybutynin+PTNS group did not complete the 6 week UDI-6 questionnaire so was not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxybutynin Plus PTNS | Change in the Urinary Distress Inventory (UDI-6) | -11.1 units on a scale |
| Placebo Plus PTNS | Change in the Urinary Distress Inventory (UDI-6) | 5.5 units on a scale |
p-value: 0.05Wilcoxon (Mann-Whitney)
Other Pre-specified
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.
Time frame: Baseline, 6 weeks
Population: Two patients in the placebo+PTN group and 1 patient in the oxybutynin+PTNS group did not complete the 6 week TSQMvII questionnaire so was not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxybutynin Plus PTNS | Change in Treatment Satisfaction Questionnaire for Medication, Version Two (TSQMvII) - Global Satisfaction Domain | 83.3 units on a scale |
| Placebo Plus PTNS | Change in Treatment Satisfaction Questionnaire for Medication, Version Two (TSQMvII) - Global Satisfaction Domain | 70.8 units on a scale |
p-value: 0.73Wilcoxon (Mann-Whitney)
Other Pre-specified
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.
Time frame: Baseline, 6 weeks
Population: Two patients in the placebo+PTN group did not complete the 6 week TSQMvII questionnaire so was not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oxybutynin Plus PTNS | Change in Treatment Satisfaction Questionnaire for Medication, Version Two (TSQMvII) - Side Effects Domain | 0 units on a scale |
| Placebo Plus PTNS | Change in Treatment Satisfaction Questionnaire for Medication, Version Two (TSQMvII) - Side Effects Domain | 0 units on a scale |
p-value: 0.94Wilcoxon (Mann-Whitney)