Overactive Bladder
Conditions
Keywords
Urinary Urgency, Urinary Frequency, Urge Incontinence
Brief summary
The aim of this study is to determine the efficacy of an accelerated course for percutaneous tibial nerve stimulation (PTNS) induction to treat overactive bladder symptoms. The standard 12 weekly induction treatments may be a patient burden and a more rapid induction may speed up symptomatic improvement.
Detailed description
Overactive bladder (OAB) is a common condition with a prevalence ranging from 5.9% to 16.9% in the United States and has been found to increase with age. OAB has a negative impact on health related quality of life (QoL), Per American Urological Association (AUA) / Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) guidelines, PTNS is a third line recommendation for OAB along with onabotulinumtoxinA (BTX) injection and sacral neuromodulation. In the single sham-controlled trial (SUmiT: n=220), Peters et al reported that 54.5% of PTNS subjects had moderately or markedly improved bladder symptoms on global response assessments (GRA) compared to 20.9% of sham subjects (p \<0.001). PTNS subjects also had statistically significant improvements in frequency, nighttime voids, voids with moderate to severe urgency and urge urinary incontinence (UUI) episodes compared to sham. There is also early data from an implanted chronic tibial nerve stimulation lead study that shows a minimum of 8 hours of tibial nerve stimulation a day results in significant improvement in incontinence episodes per day at one week. Our study will test the concept of whether the PTNS effect is dose (total time of treatment) sensitive, and whether expanding the dosage of each treatment, i.e. from 30 minutes to 2 hours, will provide significant clinical improvement after a one week induction course.
Interventions
DEVICEPTNS treatment
One-week induction consisting of three active PTNS treatments, each 2 hours long
DEVICESham treatment
One-week induction consisting of three active PTNS treatments, each 2 hours long
Sponsors
Corewell Health East
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participant blinded to interventional or sham treatment
Intervention model description
Randomized, single blind parallel assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women and men \> 18 years of age * Self-reported failed conservative care of behavioral modifications and/or oral medications * An above normal urinary frequency as recorded on initial 3-day voiding diary * Self-reported bladder symptoms greater than or equal to 3 months * On a stable dose of antimuscarinics/beta-3 agonists for greater than or equal to 4 weeks, and willing to remain on the medication for the duration of the study OR discontinued antimuscarinics/beta-3 agonists for greater than or equal to 2 weeks * Capable of giving informed consent * Ambulatory and able to use toilet independently without difficulty * Capable and willing to follow all study-related procedures
Exclusion criteria
* Pregnant or planning to become pregnant during study duration * Diagnosis of neurogenic bladder * Botox use in bladder or pelvic floor muscles within past 12 months * Pacemakers or implantable defibrillators * Current urinary tract infection * Active use of neuromodulation in any other form. If patient has InterStim, must be turned off for 2 weeks for a washout period and remain off during the entirety of the study. * Current use of Transcutaneous Electrical Nerve Stimulation (TENS) in pelvic region, back or legs * Previous PTNS treatment who received greater than 6 treatments. Those who have received less than 6 treatments will be allowed to screen if the last treatment was at least 6 months prior to screening. * Use of investigational drug/device therapy within past 4 weeks * Participation in any clinical investigation involving or impacting gynecologic, urinary or renal function within past 4 weeks * Current or past history of any physical condition that, in the investigator's opinion, might put the subject at risk or interfere with study results Note: For the sake of preserving scientific integrity, one or more of the eligibility criteria have been left off the list posted while the trial is ongoing. A full list of eligibility criteria will be posted upon completion of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in GRA for Overall Bladder Symptoms | One week post induction (+/- 3 days) | Number of subjects reporting Moderately or Markedly Improved responses on the GRA after 3 interventions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Urinary Frequency on 3 Day Voiding Diary | Baseline and 1 week post induction (+/- 3 days) | Change in number of total voids as measured by 3-day voiding diary, between pre-induction (baseline) and post-induction (post-treatment). Positive change means reduction in urinary frequency from baseline, negative change means increase in urinary frequency from baseline. |
| Change From Baseline Nocturia in 3 Day Voiding Diary | Baseline and one week post induction (+/- 3 days) | Change in number of total night time urinary voids over three days as measured by 3-day voiding diary, between pre-induction (baseline) and post-induction (post-treatment). Positive change means reduction in number of night time voids. Negative change means increase in number of night time voids. |
| Change From Baseline in Degree of Urgency in 3 Day Voiding Diary | Baseline and 1 week post induction (+/- 3 days) | Change in number of urinary voids recorded as urgent over three days as measured by 3-day voiding diary, between pre-induction (baseline) and post-induction (end of treatment). Positive change means reduction in urge incontinence episodes. Negative change means increase in urge incontinence episodes. |
| Change From Baseline in Number of Urge Incontinence Episodes in 3 Day Voiding Diary | Baseline and one week post induction (+/- 3 days) | Change in number of urge incontinence episodes over three days as measured by 3-day voiding diary, between pre-induction (baseline) and post-induction (post-treatment). Positive change means reduction in urge incontinence episodes. Negative change means increase in urge incontinence episodes. |
| Change From Baseline in Overactive Bladder Questionnaire-short Form Symptom Bother (OABq-SF) | Baseline and 1 week post induction (+/- 3 days) | Change from baseline in total score on a 6 question survey of extent of how much patients were bothered by bladder symptoms, with each question rated on a 6 point likert scale with 1= Not at all and 6= a very great deal. Score range 0-100. Higher score equals worse overactive bladder symptoms. Positive change means improvement in OAB symptoms. Negative change means worsening of OAB symptoms. |
Countries
United States
Participant flow
Recruitment details
Recruitment was primarily through physician referrals from private urology clinics. Recruitment began in March 2018 and concluded in May 2022.
Participants by arm
| Arm | Count |
|---|---|
| Active PTNS Treatment One-week induction consisting of three active PTNS treatments, each 2 hours long
PTNS treatment: One-week induction consisting of three active PTNS treatments, each 2 hours long | 13 |
| Sham Treatment One-week induction consisting of three sham treatments, each 2 hours long
Sham treatment: One-week induction consisting of three active PTNS treatments, each 2 hours long | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | Active PTNS Treatment | Sham Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 10 Participants | 19 Participants |
| Age, Continuous | 63.77 years STANDARD_DEVIATION 10.08 | 60.75 years STANDARD_DEVIATION 8.01 | 62.32 years STANDARD_DEVIATION 9.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 12 Participants | 25 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 | 0 Participants | 1 Participants | 1 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 | 13 Participants | 11 Participants | 24 Participants |
| Region of Enrollment United States | 13 participants | 12 participants | 25 participants |
| Sex: Female, Male Female | 12 Participants | 9 Participants | 21 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 6 / 13 | 2 / 12 | 3 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Improvement in GRA for Overall Bladder Symptoms
Number of subjects reporting Moderately or Markedly Improved responses on the GRA after 3 interventions
Time frame: One week post induction (+/- 3 days)
Population: One active treatment subject did not complete primary outcome
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active PTNS Treatment | Improvement in GRA for Overall Bladder Symptoms | 3 Participants |
| Sham Treatment | Improvement in GRA for Overall Bladder Symptoms | 2 Participants |
Secondary
Change From Baseline in Degree of Urgency in 3 Day Voiding Diary
Change in number of urinary voids recorded as urgent over three days as measured by 3-day voiding diary, between pre-induction (baseline) and post-induction (end of treatment). Positive change means reduction in urge incontinence episodes. Negative change means increase in urge incontinence episodes.
Time frame: Baseline and 1 week post induction (+/- 3 days)
Population: 1 active subject did not complete the diary
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active PTNS Treatment | Change From Baseline in Degree of Urgency in 3 Day Voiding Diary | 4.82 number of voids recorded as urgent | Standard Deviation 9.42 |
| Sham Treatment | Change From Baseline in Degree of Urgency in 3 Day Voiding Diary | -4.38 number of voids recorded as urgent | Standard Deviation 10.9 |
p-value: 0.0393t-test, 2 sided
Secondary
Change From Baseline in Number of Urge Incontinence Episodes in 3 Day Voiding Diary
Change in number of urge incontinence episodes over three days as measured by 3-day voiding diary, between pre-induction (baseline) and post-induction (post-treatment). Positive change means reduction in urge incontinence episodes. Negative change means increase in urge incontinence episodes.
Time frame: Baseline and one week post induction (+/- 3 days)
Population: 1 active subject did not complete a diary
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active PTNS Treatment | Change From Baseline in Number of Urge Incontinence Episodes in 3 Day Voiding Diary | 5 number of urge incontinence episodes | Standard Deviation 5.66 |
| Sham Treatment | Change From Baseline in Number of Urge Incontinence Episodes in 3 Day Voiding Diary | 2 number of urge incontinence episodes | Standard Deviation 6.43 |
p-value: 0.242t-test, 2 sided
Secondary
Change From Baseline in Overactive Bladder Questionnaire-short Form Symptom Bother (OABq-SF)
Change from baseline in total score on a 6 question survey of extent of how much patients were bothered by bladder symptoms, with each question rated on a 6 point likert scale with 1= Not at all and 6= a very great deal. Score range 0-100. Higher score equals worse overactive bladder symptoms. Positive change means improvement in OAB symptoms. Negative change means worsening of OAB symptoms.
Time frame: Baseline and 1 week post induction (+/- 3 days)
Population: 1 active subject did not complete OABq at one week visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active PTNS Treatment | Change From Baseline in Overactive Bladder Questionnaire-short Form Symptom Bother (OABq-SF) | 17.73 score on a scale | Standard Deviation 18.41 |
| Sham Treatment | Change From Baseline in Overactive Bladder Questionnaire-short Form Symptom Bother (OABq-SF) | 18.97 score on a scale | Standard Deviation 14.68 |
p-value: 0.855t-test, 2 sided
Secondary
Change From Baseline Nocturia in 3 Day Voiding Diary
Change in number of total night time urinary voids over three days as measured by 3-day voiding diary, between pre-induction (baseline) and post-induction (post-treatment). Positive change means reduction in number of night time voids. Negative change means increase in number of night time voids.
Time frame: Baseline and one week post induction (+/- 3 days)
Population: 1 active subject did not complete the diary
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active PTNS Treatment | Change From Baseline Nocturia in 3 Day Voiding Diary | -0.64 number of night time voids | Standard Deviation 2.11 |
| Sham Treatment | Change From Baseline Nocturia in 3 Day Voiding Diary | 0.31 number of night time voids | Standard Deviation 4.05 |
p-value: 0.487t-test, 2 sided
Secondary
Change From Baseline Urinary Frequency on 3 Day Voiding Diary
Change in number of total voids as measured by 3-day voiding diary, between pre-induction (baseline) and post-induction (post-treatment). Positive change means reduction in urinary frequency from baseline, negative change means increase in urinary frequency from baseline.
Time frame: Baseline and 1 week post induction (+/- 3 days)
Population: 1 active treatment subject did not complete the diary.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active PTNS Treatment | Change From Baseline Urinary Frequency on 3 Day Voiding Diary | 5 number of voids | Standard Deviation 6.21 |
| Sham Treatment | Change From Baseline Urinary Frequency on 3 Day Voiding Diary | 1.08 number of voids | Standard Deviation 5.38 |
p-value: 0.111t-test, 2 sided