TReating Incontinence for Underlying Mental and Physical Health

NCT05362292 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 21-358581R01AG075471-01
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 2

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.

Conditions

Urinary Incontinence, Urge; Urinary Incontinence; Overactive Bladder; Incontinence, Urge; Incontinence, Urinary; Incontinence

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 6 months

Secondary Outcomes (45)

• 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.

  Baseline to 9 months (3 months after end of treatment)

• Change in Auditory Verbal Learning Test total learning score assessed over 6 months (24 weeks) of treatment

  Baseline to 6 months (end of treatment)

• Change in Auditory Verbal Learning Test total learning score assessed over 9 months (36 weeks).

  Baseline to 9 months (3 months after end of treatment)

• Change Auditory Verbal Learning Test delayed free recall score over 6 months (24 weeks) of treatment.

  Baseline to 6 months (end of treatment)

• Change Auditory Verbal Learning Test delayed free recall score over 9 months (36 weeks).

  Baseline to 9 months (3 months after end of treatment)

Study Arms (3)

Anticholinergic bladder medication plus behavioral self-management education

ACTIVE COMPARATOR

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.

Drug: Tolterodine Tartrate ER

Beta-3-adrenergic agonist medication plus behavioral self-management education

ACTIVE COMPARATOR

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.

Drug: Mirabegron

Placebo medication plus behavioral self-management education

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Tolterodine Tartrate ER DRUG

Anticholinergic

Anticholinergic bladder medication plus behavioral self-management education

Mirabegron DRUG

Beta-3-adrenergic agonist

Beta-3-adrenergic agonist medication plus behavioral self-management education

Placebo DRUG

matching placebo pill

Placebo medication plus behavioral self-management education

Eligibility Criteria

• Age: 60 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Stanford University

Palo Alto, California, 94305, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94115, United States

RECRUITING

Related Publications (1)

• Huang AJ, Walter LC, Yaffe K, Vittinghoff E, Kornblith E, Schembri M, Chang A, Subak LL. TReating Incontinence for Underlying Mental and Physical Health (TRIUMPH): a study protocol for a multicenter, double-blinded, randomized, 3-arm trial to evaluate the multisystem effects of pharmacologic treatment strategies for urgency-predominant urinary incontinence in ambulatory older women. Trials. 2023 Apr 21;24(1):287. doi: 10.1186/s13063-023-07279-z.

  PMID: 37085880 DERIVED

MeSH Terms

Conditions

Urinary Incontinence, Urge; Urinary Incontinence; Urinary Bladder, Overactive

Interventions

Tolterodine Tartrate; mirabegron

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Urinary Bladder Diseases

Intervention Hierarchy (Ancestors)

Phenylpropanolamine; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Cresols; Phenols

Study Officials

• Alison Huang, MD, MAS, MPhil

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alison Huang, MD, MAS, MPhil

CONTACT

415-514-8697; alison.huang@ucsf.edu

Ann Chang

CONTACT

ann.chang@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 5, 2022
• Study Start: October 4, 2022
• Primary Completion (Estimated): May 2, 2027
• Study Completion (Estimated): August 2, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

US (2)