TReating Incontinence for Underlying Mental and Physical Health (TRIUMPH)

• ClinicalTrials.gov Identifier: NCT05362292
• Recruitment Status: Not yet recruiting
• First Posted: May 5, 2022
• Last Update Posted: May 5, 2022
• Sponsor: University of California, San Francisco
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): University of California, San Francisco

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.

Condition or disease	Intervention/treatment	Phase
Urinary Incontinence, Urge; Urinary Incontinence; Overactive Bladder; Incontinence, Urge; Incontinence, Urinary; Incontinence	Drug: Tolterodine Tartrate ER; Drug: Mirabegron; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 270 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Cognitive, Urinary, and Functional Trajectories of Older Women Using Pharmacologic Treatment Strategies for Urgency Incontinence
• Estimated Study Start Date: June 2022
• Estimated Primary Completion Date: November 2026
• Estimated Study Completion Date: February 2027

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Anticholinergic bladder medication; Tolterodine tartrate is a muscarinic receptor antagonist designed to treat urgency incontinence, urgency, and frequency associated with overactive bladder.	Drug: Tolterodine Tartrate ER; Anticholinergic
Active Comparator: Beta-3-adrenergic agonist medication; 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.	Drug: Mirabegron; Beta-3-adrenergic agonist
Placebo Comparator: Placebo medication; Microcrystalline cellulose placebo encapsulated to appear identical to tolterodine and mirabegron medication will be prepared by a compounding pharmacy.	Drug: Placebo; matching placebo pill

Outcome Measures

Primary Outcome Measures :

1. Change in composite cognitive function over 6 months of treatment, using a composite cognitive score that incorporates normalized data from all domain-specific cognitive tests. [ Time Frame: Baseline to 6 months ]
   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), in which higher scores indicate better cognitive function. 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 :

1. Change in score on verbal learning assessed from baseline to 6 months (24 weeks) of treatment. [ Time Frame: Baseline to 6 months ]
   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
2. Change in attention score from baseline to 6 months (24 weeks) of treatment. [ Time Frame: Baseline to 6 months ]
   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.
3. Change in executive function score from baseline to 6 months (24 weeks) of treatment. [ Time Frame: Baseline to 6 months ]
   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.
4. Change in short-term verbal memory score from baseline to 6 months (24 weeks) of treatment. [ Time Frame: Baseline to 6 months ]
   The Digit Span Test, 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.
5. Change in incidental memory, visual scanning, and processing speed from baseline to 6 months (24 weeks) of treatment. [ Time Frame: Baseline to 6 months ]
   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.
6. Change in frequency of urgency-type incontinence (episodes/week) from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end of treatment) ]
   Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
7. Change in frequency of any-type incontinence (episodes/week) from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end of treatment) ]
   Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
8. Resolution of urinary incontinence from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end of treatment) ]
   Frequency and type of incontinence will be assessed using a standardized, 7-day voiding diary.
9. Change in Overactive Bladder Questionnaire Short-Form (OAB-Q SF) Symptom Bother domain score from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
10. Change in Overactive Bladder Questionnaire Short-Form (OAB-Q SF) Health-Related Quality of Life domain score from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
11. Change in global sleep quality score from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
12. Change in daytime sleepiness score from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
13. Change in perceived physical function from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
14. Change in confidence in maintaining balance from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
15. Change in physical function from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
16. Change in static balance from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end of treatment) ]
    Static balance will additionally be assessed by asking participants to attempt to assume a one-legged stand for 30 seconds.
17. Change in lower extremity strength from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
18. Change in depression symptoms from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
19. Change in anxiety symptoms from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
20. Change in constipation symptoms from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end 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.
21. Change in bowel incontinence from baseline to 6 months (24 weeks). [ Time Frame: Baseline to 6 months (end of treatment) and 9 months (3 months after end of treatment) ]
    Bowel incontinence as a syndrome that frequently overlaps with urinary incontinence will be assessed using the 4-item PROMIS Bowel Incontinence scale.

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Contacts

Contact: Alison Huang, MD, MAS, MPhil; 415-514-8697; alison.huang@ucsf.edu

Contact: Ann Chang; ann.chang@ucsf.edu

Locations

United States, California

Stanford University

Palo Alto, California, United States, 94305

Contact: Leslee Subak, MD 650-723-5533 lsubak@stanford.edu

University of California San Francisco

San Francisco, California, United States, 94115

Contact: Alison Huang, MD, MAS, MPhil alison.huang@ucsf.edu

Contact: Sarah Chatfield 415-885-7547 sarah.chatfield@ucsf.edu

Sponsors and Collaborators

University of California, San Francisco

National Institute on Aging (NIA)

Investigators

• Principal Investigator: Alison Huang, MD, MAS, MPhil; University of California, San Francisco

More Information

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT05362292
• Other Study ID Numbers: 21-35858; 1R01AG075471-01 ( U.S. NIH Grant/Contract )
• First Posted: May 5, 2022
• Last Update Posted: May 5, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Informed Consent Form (ICF)
• 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.

• 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

Additional relevant MeSH terms:

Urinary Incontinence; Enuresis; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urination Disorders; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Behavioral Symptoms; Elimination Disorders; Mental Disorders; Urinary Bladder Diseases; Mirabegron; Tolterodine Tartrate; Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Urological Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents