Back to resultsTReating Incontinence for Underlying Mental and Physical Health (TRIUMPH)
Primary Purpose
Urinary Incontinence, Urge, Urinary Incontinence, Overactive Bladder
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Tolterodine Tartrate ER
Mirabegron
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Urinary Incontinence, Urge
Eligibility Criteria
Inclusion Criteria:
- Aged 60 years or older at the time of enrollment
- Female sex at birth, without surgical or hormonal gender re-assignment therapy
- Able to walk to the bathroom and use the toilet without assistance
- Report urinary incontinence starting at least 3 months prior to screening
- Report that at least half of incontinence episodes occur with a sudden or strong sensation of urgency
- Report 2 or more urgency incontinence episodes over a 7-day period
- Willing to provide informed consent and adhere to study procedures throughout the length of the study
Exclusion Criteria:
- Prior clinician diagnosis of dementia, or a Montreal Cognitive Assessment (MOCA) score of 17 or lower on screening cognitive evaluation
- Current use of anticholinergic, beta-3-adrenergic agonist, or other medication designed to improve urgency incontinence symptoms, or use in the past 1 month
- Initiation, discontinuation, or dose change of dementia medications (such as donepezil, galantamine, memantine, rivastigmine) in the past 1 month (but candidates on stable doses are eligible)
- Initiation, discontinuation, or dose change of other drugs with strong anticholinergic effects (based on the Beers List) in the past 1 month (but candidates on stable doses are eligible)
- Initiation, discontinuation, or dose change of other drugs that can affect urinary frequency, including diuretics, in the past 1 month (but candidates on stable doses are eligible)
- Current urinary tract infection (UTI) based on screening urinalysis and culture (but candidates can re-present for re-screening after undergoing treatment for UTI)
- History of allergy or sensitivity to either of the study medications or an ingredient in the placebo or study medication capsule
- Severe hepatic impairment (Child-Pugh score B or greater) or renal impairment (creatinine clearance <30 mL/min) as a contraindication to both study medications
- Current bladder obstruction or urinary retention (defined by symptoms suggesting difficulty emptying the bladder in addition to postvoid residual urine volume greater than 150 cc by portable bladder ultrasound)
- Uncontrolled hypertension (based on measured systolic blood pressure greater than 180 or diastolic blood pressure greater than 110 mmHg) as a contraindication to beta-3-adrenergic therapy
- Self-reported history of gastric retention, uncontrolled narrow angle glaucoma, myasthenia gravis, severe ulcerative colitis, or toxic megacolon as contraindications for anticholinergic bladder therapy
- Use of drugs with adverse interactions with one of the study medications in the past 1 month, including potent CYP3A4 inhibitors, hepatic enzyme metabolism inducers, narrow therapeutic index drugs metabolized by CYP2D6, or intention to start taking one of these medications during the study treatment period
- History of bladder surgery, invasive intra-vesical therapy, or bulk bladder injections in the past 3 months (more remote surgery will not be exclusionary), or intention to undergo one of these procedures in the study treatment period
- Use of other specialized incontinence therapy (electrostimulation, pelvic physiotherapy, formal behavioral therapy overseen by certified practitioners) in the past 3 months (more remote therapy will not be exclusionary), or intention to undergo one of these procedures in the study treatment period
- Inability to sign informed consent or complete questionnaires, interviews, or study testing in English
- Other condition that would prevent the participant from completing study procedures, in the opinion of the investigators (e.g., uncontrolled psychosis)
Sites / Locations
- Stanford UniversityRecruiting
- University of California San FranciscoRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Anticholinergic bladder medication plus behavioral self-management education
Beta-3-adrenergic agonist medication plus behavioral self-management education
Placebo medication plus behavioral self-management education
Arm Description
Tolterodine tartrate is a muscarinic receptor antagonist designed to treat urgency incontinence, urgency, and frequency associated with overactive bladder. Behavioral self-management education includes written education about timed urination, lifestyle changes, pelvic floor muscle exercises, and urge suppression.
Mirabegron, currently sold under the brand name Mybetriq by Astellas Pharma, is a selective beta-3-adrenergic receptor agonist approved for treatment of urgency urinary incontinence, urgency, and frequency associated with overactive bladder. Behavioral self-management education includes written education about timed urination, lifestyle changes, pelvic floor muscle exercises, and urge suppression.
Microcrystalline cellulose placebo encapsulated to appear identical to tolterodine and mirabegron medication will be prepared by a compounding pharmacy. Behavioral self-management education includes written education about timed urination, lifestyle changes, pelvic floor muscle exercises, and urge suppression.
Outcomes
Primary Outcome Measures
Change in composite cognitive function over 6 months (24 weeks) of treatment, using a composite cognitive score that incorporates normalized data from all domain-specific cognitive tests.
The composite cognitive score will be calculated as the average of Z-scores from the following individual cognitive tests: a) Auditory Verbal Learning Test (AVLT); b) Oral Trail Making Test (OTMT) part A; c) OTMT part B; d) Digit Span Test; and e) Digit Symbol Substitution Test (DSST). The normative mean of each cognitive test will be subtracted from each participant's component test score, and this difference will be divided by the standard deviation for the appropriate normative sample. After scores from individual tests are transformed to Z scores as a common metric based on normative data, the average Z score from all available tests will be calculated to provide a composite Z score.
Secondary Outcome Measures
Change in composite cognitive function over 9 months (36 weeks), using a composite cognitive score that incorporates normalized data from all domain-specific cognitive tests.
The composite cognitive score will be calculated as the average of Z-scores from the following individual cognitive tests: a) Auditory Verbal Learning Test (AVLT); b) Oral Trail Making Test (OTMT) part A; c) OTMT part B; d) Digit Span Test; and e) Digit Symbol Substitution Test (DSST). The normative mean of each cognitive test will be subtracted from each participant's component test score, and this difference will be divided by the standard deviation for the appropriate normative sample. After scores from individual tests are transformed to Z scores as a common metric based on normative data, the average Z score from all available tests will be calculated to provide a composite Z score.
Change in Auditory Verbal Learning Test total learning score assessed over 6 months (24 weeks) of treatment
The Rey Auditory Verbal Learning Test (AVLT), a widely used test of immediate and delayed verbal learning with established norms in older adults and multiple alternate forms. The total learning score is the sum of words learned from trials 1-5.
Change in Auditory Verbal Learning Test total learning score assessed over 9 months (36 weeks).
The Rey Auditory Verbal Learning Test (AVLT), a widely used test of immediate and delayed verbal learning with established norms in older adults and multiple alternate forms. The total learning score is the sum of words learned from trials 1-5.
Change Auditory Verbal Learning Test delayed free recall score over 6 months (24 weeks) of treatment.
The Rey Auditory Verbal Learning Test (AVLT), a widely used test of immediate and delayed verbal learning with established norms in older adults and multiple alternate forms. Score range of 0-15.
Change Auditory Verbal Learning Test delayed free recall score over 9 months (36 weeks).
The Rey Auditory Verbal Learning Test (AVLT), a widely used test of immediate and delayed verbal learning with established norms in older adults and multiple alternate forms. Score range of 0-15.
Change in Oral Trail Making A score over 6 months (24 weeks) of treatment.
The oral version of the Trail Making Test (OTMT), a timed measure of attention (part A) and executive function (part B) adapted from the written TMT, with established norms for participants across a wide range of ages. Range of 1-150 seconds
Change in Oral Trail Making A score over 9 months (36 weeks).
The oral version of the Trail Making Test (OTMT), a timed measure of attention (part A) and executive function (part B) adapted from the written TMT, with established norms for participants across a wide range of ages. Range of 1-150 seconds
Change in Oral Trail Making B score over 6 months (24 weeks) of treatment.
The oral version of the Trail Making Test (OTMT), a timed measure of attention (part A) and executive function (part B) adapted from the written TMT, with established norms for participants across a wide range of ages. Range of 1-300 seconds.
Change in Oral Trail Making B score over 9 months (36 weeks).
The oral version of the Trail Making Test (OTMT), a timed measure of attention (part A) and executive function (part B) adapted from the written TMT, with established norms for participants across a wide range of ages. Range of 1-300 seconds.
Change in Digit Span reverse component (total correct trials) over 6 months (24 weeks) of treatment.
The Digit Span Reverse (total correct trials), a subtest of the Wechsler Adult Intelligence and Memory Scales, a test of attention and short-term verbal memory, with reliability across in-person and videoconference platforms. Range of 0-14.
Change in Digit Span reverse component (total correct trials) over 9 months (36 weeks).
The Digit Span Reverse (total correct trials), a subtest of the Wechsler Adult Intelligence and Memory Scales, a test of attention and short-term verbal memory, with reliability across in-person and videoconference platforms. Range of 0-14.
Change in Digit Symbol Substitution Test score over 6 months (24 weeks) of treatment.
The Digit Symbol Substitution Test (DSST), a timed, written test assessing incidental memory, visual scanning, and processing speed, in which subjects translate numbers into symbols using a key. Range of 1-133.
Change in Digit Symbol Substitution Test score over 9 months (36 weeks).
The Digit Symbol Substitution Test (DSST), a timed, written test assessing incidental memory, visual scanning, and processing speed, in which subjects translate numbers into symbols using a key. Range of 1-133.
Change in frequency of urgency-type incontinence (episodes/week) over 6 months (24 weeks) of treatment.
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Change in frequency of urgency-type incontinence (episodes/week) over 9 months (36 weeks).
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Change in frequency of any-type incontinence (episodes/week) over 6 months (24 weeks) of treatment.
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Change in frequency of any-type incontinence (episodes/week) over 9 months (36 weeks).
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Resolution of urinary incontinence from baseline to 6 months (24 weeks).
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Resolution of urinary incontinence from baseline to 9 months (36 weeks).
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Change in Overactive Bladder Questionnaire Short-Form (OAB-Q SF) Symptom Bother domain score over 6 months (24 weeks) of treatment.
Bothersomeness and impact of overactive bladder symptoms (such as urgency, incontinence, and nocturia) will be assessed using the short-form of the OAB-Q, which generates both a Symptom Bother domain and a Health-Related Quality of Life domain score.
Change in Overactive Bladder Questionnaire Short-Form (OAB-Q SF) Symptom Bother domain score over 9 months (36 weeks).
Bothersomeness and impact of overactive bladder symptoms (such as urgency, incontinence, and nocturia) will be assessed using the short-form of the OAB-Q, which generates both a Symptom Bother domain and a Health-Related Quality of Life domain score.
Change in Overactive Bladder Questionnaire Short-Form (OAB-Q SF) Health-Related Quality of Life domain score over 6 months (24 weeks) of treatment.
Bothersomeness and impact of overactive bladder symptoms (such as urgency, incontinence, and nocturia) will be assessed using the short-form of the OAB-Q, which generates both a Symptom Bother domain and a Health-Related Quality of Life domain score.
Change in Overactive Bladder Questionnaire Short-Form (OAB-Q SF) Health-Related Quality of Life domain score over 9 months (36 weeks).
Bothersomeness and impact of overactive bladder symptoms (such as urgency, incontinence, and nocturia) will be assessed using the short-form of the OAB-Q, which generates both a Symptom Bother domain and a Health-Related Quality of Life domain score.
Change in global sleep quality score over 6 months (24 weeks) of treatment.
Perceived sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), an 18-item validated questionnaire designed to assess sleep quality, latency, efficiency, and problems over a one-week period.
Change in global sleep quality score over 9 months (36 weeks).
Perceived sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), an 18-item validated questionnaire designed to assess sleep quality, latency, efficiency, and problems over a one-week period.
Change in daytime sleepiness score over 6 months (24 weeks) of treatment.
Daytime sleepiness will be assessed using the Epworth Sleepiness Scale (ESS), an 8-item questionnaire assessing the level of general sleepiness during real life situations in order to distinguish excessive daytime sleepiness from normal daytime sleepiness.
Change in daytime sleepiness score over 9 months (36 weeks).
Daytime sleepiness will be assessed using the Epworth Sleepiness Scale (ESS), an 8-item questionnaire assessing the level of general sleepiness during real life situations in order to distinguish excessive daytime sleepiness from normal daytime sleepiness.
Change in perceived physical function over 6 months (24 weeks) of treatment.
Perceived physical function will be assessed using the PROMIS 10B Adult Physical Function Scale, a 10-item measure that assesses the extent to which daily activities are limited by function of the extremities and central regions.
Change in perceived physical function over 9 months (36 weeks).
Perceived physical function will be assessed using the PROMIS 10B Adult Physical Function Scale, a 10-item measure that assesses the extent to which daily activities are limited by function of the extremities and central regions.
Change in confidence in maintaining balance over 6 months (24 weeks) of treatment.
Confidence in maintaining balance will be assessed using the 15-item Activities Balance Confidence Scale (ABC-S), in which participants self-rate their confidence in keeping balance with performing daily living tasks.
Change in confidence in maintaining balance over 9 months (36 weeks).
Confidence in maintaining balance will be assessed using the 15-item Activities Balance Confidence Scale (ABC-S), in which participants self-rate their confidence in keeping balance with performing daily living tasks.
Change in overall physical performance over 6 months (24 weeks) of treatment.
Physical function will be directly assessed using the Short Physical Performance Battery (SPPB), involving: 1) side-by-side, semi-tandem, and tandem balance tests; 2) a 4-meter walk test; and 3) 5 chair stands, in which participants will be asked to stand up repeatedly from a standard chair to a full extended standing position.
Change in overall physical performance over 9 months (36 weeks).
Physical function will be directly assessed using the Short Physical Performance Battery (SPPB), involving: 1) side-by-side, semi-tandem, and tandem balance tests; 2) a 4-meter walk test; and 3) 5 chair stands, in which participants will be asked to stand up repeatedly from a standard chair to a full extended standing position.
Change in static balance over 6 months (24 weeks) of treatment.
Static balance will additionally be assessed by asking participants to attempt to assume a one-legged stand for 30 seconds.
Change in static balance from over 9 months (36 weeks).
Static balance will additionally be assessed by asking participants to attempt to assume a one-legged stand for 30 seconds.
Change in lower extremity strength measured by chair stand testing over 6 months (24 weeks) of treatment.
Physical strength will be assessed 30-second chair stand, by asking participants to stand up as many times as possible within 30 seconds, with higher number indicating more strength or power.
Change in lower extremity strength measured by chair stand testing over 9 months (36 weeks).
Physical strength will be assessed 30-second chair stand, by asking participants to stand up as many times as possible within 30 seconds, with higher number indicating more strength or power.
Change in depression symptoms over 6 months (24 weeks) of treatment.
Depression symptoms will be assessed using the 15-item short form of the Geriatric Depression Scale-15 (GDS-15), which assesses symptoms of depression over a 1-week period.
Change in depression symptoms over 9 months (36 weeks).
Depression symptoms will be assessed using the 15-item short form of the Geriatric Depression Scale-15 (GDS-15), which assesses symptoms of depression over a 1-week period.
Change in anxiety symptoms over 6 months (24 weeks) of treatment.
Anxiety symptoms will be assessing using the Generalized Anxiety Disorder-7 (GAD7), 7-item short form, questionnaire to assess severity of anxiety symptoms over a 2-week period.
Change in anxiety symptoms over 9 months (36 weeks).
Anxiety symptoms will be assessing using the Generalized Anxiety Disorder-7 (GAD7), 7-item short form, questionnaire to assess severity of anxiety symptoms over a 2-week period.
Change in constipation symptoms over 6 months (24 weeks) of treatment.
Symptoms of constipation as a possible side effect of anticholinergic therapy will be assessed by the 9-item PROMIS Constipation scale of the PROMIS Gastrointestinal Symptoms-Constipation Scale.
Change in constipation symptoms over 9 months (36 weeks).
Symptoms of constipation as a possible side effect of anticholinergic therapy will be assessed by the 9-item PROMIS Constipation scale of the PROMIS Gastrointestinal Symptoms-Constipation Scale.
Change in bowel incontinence symptoms over 6 months (24 weeks) of treatment.
Bowel incontinence as a syndrome that frequently overlaps with urinary incontinence will be assessed using the 4-item PROMIS Bowel Incontinence scale.
Change in bowel incontinence symptoms over 9 months (36 weeks).
Bowel incontinence as a syndrome that frequently overlaps with urinary incontinence will be assessed using the 4-item PROMIS Bowel Incontinence scale.
Full Information
NCT ID
NCT05362292
First Posted
May 2, 2022
Last Updated
December 7, 2022
Sponsor
University of California, San Francisco
Collaborators
National Institute on Aging (NIA)
1. Study Identification
Unique Protocol Identification Number
NCT05362292
Brief Title
TReating Incontinence for Underlying Mental and Physical Health
Acronym
TRIUMPH
Official Title
Cognitive, Urinary, and Functional Trajectories of Older Women Using Pharmacologic Treatment Strategies for Urgency Incontinence
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 4, 2022 (Actual)
Primary Completion Date
September 28, 2026 (Anticipated)
Study Completion Date
December 28, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
National Institute on Aging (NIA)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The TRIUMPH study is a randomized, double-blinded, 3-arm, parallel-group trial designed to compare the effects of anticholinergic bladder therapy versus a) beta-3-adrenergic agonist bladder therapy and b) no bladder pharmacotherapy on cognitive, urinary, and other aging-related functional outcomes in ambulatory older women with urgency-predominant urinary incontinence and either normal or mildly impaired cognitive function at baseline.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urinary Incontinence, Urge, Urinary Incontinence, Overactive Bladder, Incontinence, Urge, Incontinence, Urinary, Incontinence
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
270 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Anticholinergic bladder medication plus behavioral self-management education
Arm Type
Active Comparator
Arm Description
Tolterodine tartrate is a muscarinic receptor antagonist designed to treat urgency incontinence, urgency, and frequency associated with overactive bladder. Behavioral self-management education includes written education about timed urination, lifestyle changes, pelvic floor muscle exercises, and urge suppression.
Arm Title
Beta-3-adrenergic agonist medication plus behavioral self-management education
Arm Type
Active Comparator
Arm Description
Mirabegron, currently sold under the brand name Mybetriq by Astellas Pharma, is a selective beta-3-adrenergic receptor agonist approved for treatment of urgency urinary incontinence, urgency, and frequency associated with overactive bladder. Behavioral self-management education includes written education about timed urination, lifestyle changes, pelvic floor muscle exercises, and urge suppression.
Arm Title
Placebo medication plus behavioral self-management education
Arm Type
Placebo Comparator
Arm Description
Microcrystalline cellulose placebo encapsulated to appear identical to tolterodine and mirabegron medication will be prepared by a compounding pharmacy. Behavioral self-management education includes written education about timed urination, lifestyle changes, pelvic floor muscle exercises, and urge suppression.
Intervention Type
Drug
Intervention Name(s)
Tolterodine Tartrate ER
Intervention Description
Anticholinergic
Intervention Type
Drug
Intervention Name(s)
Mirabegron
Intervention Description
Beta-3-adrenergic agonist
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
matching placebo pill
Primary Outcome Measure Information:
Title
Change in composite cognitive function over 6 months (24 weeks) of treatment, using a composite cognitive score that incorporates normalized data from all domain-specific cognitive tests.
Description
The composite cognitive score will be calculated as the average of Z-scores from the following individual cognitive tests: a) Auditory Verbal Learning Test (AVLT); b) Oral Trail Making Test (OTMT) part A; c) OTMT part B; d) Digit Span Test; and e) Digit Symbol Substitution Test (DSST). The normative mean of each cognitive test will be subtracted from each participant's component test score, and this difference will be divided by the standard deviation for the appropriate normative sample. After scores from individual tests are transformed to Z scores as a common metric based on normative data, the average Z score from all available tests will be calculated to provide a composite Z score.
Time Frame
Baseline to 6 months
Secondary Outcome Measure Information:
Title
Change in composite cognitive function over 9 months (36 weeks), using a composite cognitive score that incorporates normalized data from all domain-specific cognitive tests.
Description
The composite cognitive score will be calculated as the average of Z-scores from the following individual cognitive tests: a) Auditory Verbal Learning Test (AVLT); b) Oral Trail Making Test (OTMT) part A; c) OTMT part B; d) Digit Span Test; and e) Digit Symbol Substitution Test (DSST). The normative mean of each cognitive test will be subtracted from each participant's component test score, and this difference will be divided by the standard deviation for the appropriate normative sample. After scores from individual tests are transformed to Z scores as a common metric based on normative data, the average Z score from all available tests will be calculated to provide a composite Z score.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in Auditory Verbal Learning Test total learning score assessed over 6 months (24 weeks) of treatment
Description
The Rey Auditory Verbal Learning Test (AVLT), a widely used test of immediate and delayed verbal learning with established norms in older adults and multiple alternate forms. The total learning score is the sum of words learned from trials 1-5.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in Auditory Verbal Learning Test total learning score assessed over 9 months (36 weeks).
Description
The Rey Auditory Verbal Learning Test (AVLT), a widely used test of immediate and delayed verbal learning with established norms in older adults and multiple alternate forms. The total learning score is the sum of words learned from trials 1-5.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change Auditory Verbal Learning Test delayed free recall score over 6 months (24 weeks) of treatment.
Description
The Rey Auditory Verbal Learning Test (AVLT), a widely used test of immediate and delayed verbal learning with established norms in older adults and multiple alternate forms. Score range of 0-15.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change Auditory Verbal Learning Test delayed free recall score over 9 months (36 weeks).
Description
The Rey Auditory Verbal Learning Test (AVLT), a widely used test of immediate and delayed verbal learning with established norms in older adults and multiple alternate forms. Score range of 0-15.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in Oral Trail Making A score over 6 months (24 weeks) of treatment.
Description
The oral version of the Trail Making Test (OTMT), a timed measure of attention (part A) and executive function (part B) adapted from the written TMT, with established norms for participants across a wide range of ages. Range of 1-150 seconds
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in Oral Trail Making A score over 9 months (36 weeks).
Description
The oral version of the Trail Making Test (OTMT), a timed measure of attention (part A) and executive function (part B) adapted from the written TMT, with established norms for participants across a wide range of ages. Range of 1-150 seconds
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in Oral Trail Making B score over 6 months (24 weeks) of treatment.
Description
The oral version of the Trail Making Test (OTMT), a timed measure of attention (part A) and executive function (part B) adapted from the written TMT, with established norms for participants across a wide range of ages. Range of 1-300 seconds.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in Oral Trail Making B score over 9 months (36 weeks).
Description
The oral version of the Trail Making Test (OTMT), a timed measure of attention (part A) and executive function (part B) adapted from the written TMT, with established norms for participants across a wide range of ages. Range of 1-300 seconds.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in Digit Span reverse component (total correct trials) over 6 months (24 weeks) of treatment.
Description
The Digit Span Reverse (total correct trials), a subtest of the Wechsler Adult Intelligence and Memory Scales, a test of attention and short-term verbal memory, with reliability across in-person and videoconference platforms. Range of 0-14.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in Digit Span reverse component (total correct trials) over 9 months (36 weeks).
Description
The Digit Span Reverse (total correct trials), a subtest of the Wechsler Adult Intelligence and Memory Scales, a test of attention and short-term verbal memory, with reliability across in-person and videoconference platforms. Range of 0-14.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in Digit Symbol Substitution Test score over 6 months (24 weeks) of treatment.
Description
The Digit Symbol Substitution Test (DSST), a timed, written test assessing incidental memory, visual scanning, and processing speed, in which subjects translate numbers into symbols using a key. Range of 1-133.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in Digit Symbol Substitution Test score over 9 months (36 weeks).
Description
The Digit Symbol Substitution Test (DSST), a timed, written test assessing incidental memory, visual scanning, and processing speed, in which subjects translate numbers into symbols using a key. Range of 1-133.
Time Frame
Baseline 9 months (3 months after end of treatment)
Title
Change in frequency of urgency-type incontinence (episodes/week) over 6 months (24 weeks) of treatment.
Description
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in frequency of urgency-type incontinence (episodes/week) over 9 months (36 weeks).
Description
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in frequency of any-type incontinence (episodes/week) over 6 months (24 weeks) of treatment.
Description
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in frequency of any-type incontinence (episodes/week) over 9 months (36 weeks).
Description
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Resolution of urinary incontinence from baseline to 6 months (24 weeks).
Description
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Time Frame
Baseline to 6 months (end of treatment)
Title
Resolution of urinary incontinence from baseline to 9 months (36 weeks).
Description
Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in Overactive Bladder Questionnaire Short-Form (OAB-Q SF) Symptom Bother domain score over 6 months (24 weeks) of treatment.
Description
Bothersomeness and impact of overactive bladder symptoms (such as urgency, incontinence, and nocturia) will be assessed using the short-form of the OAB-Q, which generates both a Symptom Bother domain and a Health-Related Quality of Life domain score.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in Overactive Bladder Questionnaire Short-Form (OAB-Q SF) Symptom Bother domain score over 9 months (36 weeks).
Description
Bothersomeness and impact of overactive bladder symptoms (such as urgency, incontinence, and nocturia) will be assessed using the short-form of the OAB-Q, which generates both a Symptom Bother domain and a Health-Related Quality of Life domain score.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in Overactive Bladder Questionnaire Short-Form (OAB-Q SF) Health-Related Quality of Life domain score over 6 months (24 weeks) of treatment.
Description
Bothersomeness and impact of overactive bladder symptoms (such as urgency, incontinence, and nocturia) will be assessed using the short-form of the OAB-Q, which generates both a Symptom Bother domain and a Health-Related Quality of Life domain score.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in Overactive Bladder Questionnaire Short-Form (OAB-Q SF) Health-Related Quality of Life domain score over 9 months (36 weeks).
Description
Bothersomeness and impact of overactive bladder symptoms (such as urgency, incontinence, and nocturia) will be assessed using the short-form of the OAB-Q, which generates both a Symptom Bother domain and a Health-Related Quality of Life domain score.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in global sleep quality score over 6 months (24 weeks) of treatment.
Description
Perceived sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), an 18-item validated questionnaire designed to assess sleep quality, latency, efficiency, and problems over a one-week period.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in global sleep quality score over 9 months (36 weeks).
Description
Perceived sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), an 18-item validated questionnaire designed to assess sleep quality, latency, efficiency, and problems over a one-week period.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in daytime sleepiness score over 6 months (24 weeks) of treatment.
Description
Daytime sleepiness will be assessed using the Epworth Sleepiness Scale (ESS), an 8-item questionnaire assessing the level of general sleepiness during real life situations in order to distinguish excessive daytime sleepiness from normal daytime sleepiness.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in daytime sleepiness score over 9 months (36 weeks).
Description
Daytime sleepiness will be assessed using the Epworth Sleepiness Scale (ESS), an 8-item questionnaire assessing the level of general sleepiness during real life situations in order to distinguish excessive daytime sleepiness from normal daytime sleepiness.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in perceived physical function over 6 months (24 weeks) of treatment.
Description
Perceived physical function will be assessed using the PROMIS 10B Adult Physical Function Scale, a 10-item measure that assesses the extent to which daily activities are limited by function of the extremities and central regions.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in perceived physical function over 9 months (36 weeks).
Description
Perceived physical function will be assessed using the PROMIS 10B Adult Physical Function Scale, a 10-item measure that assesses the extent to which daily activities are limited by function of the extremities and central regions.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in confidence in maintaining balance over 6 months (24 weeks) of treatment.
Description
Confidence in maintaining balance will be assessed using the 15-item Activities Balance Confidence Scale (ABC-S), in which participants self-rate their confidence in keeping balance with performing daily living tasks.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in confidence in maintaining balance over 9 months (36 weeks).
Description
Confidence in maintaining balance will be assessed using the 15-item Activities Balance Confidence Scale (ABC-S), in which participants self-rate their confidence in keeping balance with performing daily living tasks.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in overall physical performance over 6 months (24 weeks) of treatment.
Description
Physical function will be directly assessed using the Short Physical Performance Battery (SPPB), involving: 1) side-by-side, semi-tandem, and tandem balance tests; 2) a 4-meter walk test; and 3) 5 chair stands, in which participants will be asked to stand up repeatedly from a standard chair to a full extended standing position.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in overall physical performance over 9 months (36 weeks).
Description
Physical function will be directly assessed using the Short Physical Performance Battery (SPPB), involving: 1) side-by-side, semi-tandem, and tandem balance tests; 2) a 4-meter walk test; and 3) 5 chair stands, in which participants will be asked to stand up repeatedly from a standard chair to a full extended standing position.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in static balance over 6 months (24 weeks) of treatment.
Description
Static balance will additionally be assessed by asking participants to attempt to assume a one-legged stand for 30 seconds.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in static balance from over 9 months (36 weeks).
Description
Static balance will additionally be assessed by asking participants to attempt to assume a one-legged stand for 30 seconds.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in lower extremity strength measured by chair stand testing over 6 months (24 weeks) of treatment.
Description
Physical strength will be assessed 30-second chair stand, by asking participants to stand up as many times as possible within 30 seconds, with higher number indicating more strength or power.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in lower extremity strength measured by chair stand testing over 9 months (36 weeks).
Description
Physical strength will be assessed 30-second chair stand, by asking participants to stand up as many times as possible within 30 seconds, with higher number indicating more strength or power.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in depression symptoms over 6 months (24 weeks) of treatment.
Description
Depression symptoms will be assessed using the 15-item short form of the Geriatric Depression Scale-15 (GDS-15), which assesses symptoms of depression over a 1-week period.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in depression symptoms over 9 months (36 weeks).
Description
Depression symptoms will be assessed using the 15-item short form of the Geriatric Depression Scale-15 (GDS-15), which assesses symptoms of depression over a 1-week period.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in anxiety symptoms over 6 months (24 weeks) of treatment.
Description
Anxiety symptoms will be assessing using the Generalized Anxiety Disorder-7 (GAD7), 7-item short form, questionnaire to assess severity of anxiety symptoms over a 2-week period.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in anxiety symptoms over 9 months (36 weeks).
Description
Anxiety symptoms will be assessing using the Generalized Anxiety Disorder-7 (GAD7), 7-item short form, questionnaire to assess severity of anxiety symptoms over a 2-week period.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in constipation symptoms over 6 months (24 weeks) of treatment.
Description
Symptoms of constipation as a possible side effect of anticholinergic therapy will be assessed by the 9-item PROMIS Constipation scale of the PROMIS Gastrointestinal Symptoms-Constipation Scale.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in constipation symptoms over 9 months (36 weeks).
Description
Symptoms of constipation as a possible side effect of anticholinergic therapy will be assessed by the 9-item PROMIS Constipation scale of the PROMIS Gastrointestinal Symptoms-Constipation Scale.
Time Frame
Baseline to 9 months (3 months after end of treatment)
Title
Change in bowel incontinence symptoms over 6 months (24 weeks) of treatment.
Description
Bowel incontinence as a syndrome that frequently overlaps with urinary incontinence will be assessed using the 4-item PROMIS Bowel Incontinence scale.
Time Frame
Baseline to 6 months (end of treatment)
Title
Change in bowel incontinence symptoms over 9 months (36 weeks).
Description
Bowel incontinence as a syndrome that frequently overlaps with urinary incontinence will be assessed using the 4-item PROMIS Bowel Incontinence scale.
Time Frame
Baseline to 9 months (3 months after end of treatment)
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Aged 60 years or older at the time of enrollment
Female sex at birth, without surgical or hormonal gender re-assignment therapy
Able to walk to the bathroom and use the toilet without assistance
Report urinary incontinence starting at least 3 months prior to screening
Report that at least half of incontinence episodes occur with a sudden or strong sensation of urgency
Report 2 or more urgency incontinence episodes over a 7-day period
Willing to provide informed consent and adhere to study procedures throughout the length of the study
Exclusion Criteria:
Prior clinician diagnosis of dementia, or a Montreal Cognitive Assessment (MOCA) score of 17 or lower on screening cognitive evaluation
Current use of anticholinergic, beta-3-adrenergic agonist, or other medication designed to improve urgency incontinence symptoms, or use in the past 1 month
Initiation, discontinuation, or dose change of dementia medications (such as donepezil, galantamine, memantine, rivastigmine) in the past 1 month (but candidates on stable doses are eligible)
Initiation, discontinuation, or dose change of other drugs with strong anticholinergic effects (based on the Beers List) in the past 1 month (but candidates on stable doses are eligible)
Initiation, discontinuation, or dose change of other drugs that can affect urinary frequency, including diuretics, in the past 1 month (but candidates on stable doses are eligible)
Current urinary tract infection (UTI) based on screening urinalysis and culture (but candidates can re-present for re-screening after undergoing treatment for UTI)
History of allergy or sensitivity to either of the study medications or an ingredient in the placebo or study medication capsule
Severe hepatic impairment (Child-Pugh score B or greater) or renal impairment (creatinine clearance <30 mL/min) as a contraindication to both study medications
Current bladder obstruction or urinary retention (defined by symptoms suggesting difficulty emptying the bladder in addition to postvoid residual urine volume greater than 150 cc by portable bladder ultrasound)
Uncontrolled hypertension (based on measured systolic blood pressure greater than 180 or diastolic blood pressure greater than 110 mmHg) as a contraindication to beta-3-adrenergic therapy
Self-reported history of gastric retention, uncontrolled narrow angle glaucoma, myasthenia gravis, severe ulcerative colitis, or toxic megacolon as contraindications for anticholinergic bladder therapy
Use of drugs with adverse interactions with one of the study medications in the past 1 month, including potent CYP3A4 inhibitors, hepatic enzyme metabolism inducers, narrow therapeutic index drugs metabolized by CYP2D6, or intention to start taking one of these medications during the study treatment period
History of bladder surgery, invasive intra-vesical therapy, or bulk bladder injections in the past 3 months (more remote surgery will not be exclusionary), or intention to undergo one of these procedures in the study treatment period
Use of other specialized incontinence therapy (electrostimulation, pelvic physiotherapy, formal behavioral therapy overseen by certified practitioners) in the past 3 months (more remote therapy will not be exclusionary), or intention to undergo one of these procedures in the study treatment period
Inability to sign informed consent or complete questionnaires, interviews, or study testing in English
Other condition that would prevent the participant from completing study procedures, in the opinion of the investigators (e.g., uncontrolled psychosis)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alison Huang, MD, MAS, MPhil
Phone
415-514-8697
Email
alison.huang@ucsf.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Ann Chang
Email
ann.chang@ucsf.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alison Huang, MD, MAS, MPhil
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leslee Subak, MD
Phone
650-723-5533
Email
lsubak@stanford.edu
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alison Huang, MD, MAS, MPhil
Email
alison.huang@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Sarah Chatfield
Phone
415-885-7547
Email
sarah.chatfield@ucsf.edu
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The investigative team will make publicly available de-identified individual participant data that underlie the results reported in the publication. This will include data about the baseline characteristics of enrolled participants and any primary or secondary trial outcomes presented in the publication. To gain access, data requestors will be asked to sign a data access agreement.
IPD Sharing Time Frame
Starting no later than 6 months following publication of the main trial results (including on-line publication), the investigative team will make publicly available de-identified individual participant data that underlie the results reported in the publication. This will include data about the baseline characteristics of the study participants and any primary or secondary trial outcomes presented in the publication.
Learn more about this trial
TReating Incontinence for Underlying Mental and Physical Health
We'll reach out to this number within 24 hrs