TReating Incontinence for Underlying Mental and Physical Health

Official title

Cognitive, Urinary, and Functional Trajectories of Older Women Using Pharmacologic Treatment Strategies for Urgency Incontinence

Overview

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.

Interventions

• Drug Tolterodine Tartrate ER
  Anticholinergic
• Drug Mirabegron
  Beta-3-adrenergic agonist
• Drug Placebo
  matching placebo pill

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. [Time frame: Baseline to 6 months]

Secondary outcome measures (12)

• 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. [Time frame: 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 [Time frame: Baseline to 6 months (end of treatment)]
• Change in Auditory Verbal Learning Test total learning score assessed over 9 months (36 weeks). [Time frame: 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. [Time frame: Baseline to 6 months (end of treatment)]
• Change Auditory Verbal Learning Test delayed free recall score over 9 months (36 weeks). [Time frame: Baseline to 9 months (3 months after end of treatment)]
• Change in Oral Trail Making A score over 6 months (24 weeks) of treatment. [Time frame: Baseline to 6 months (end of treatment)]
• Change in Oral Trail Making A score over 9 months (36 weeks). [Time frame: Baseline to 9 months (3 months after end of treatment)]
• Change in Oral Trail Making B score over 6 months (24 weeks) of treatment. [Time frame: Baseline to 6 months (end of treatment)]
• Change in Oral Trail Making B score over 9 months (36 weeks). [Time frame: Baseline to 9 months (3 months after end of treatment)]
• Change in Digit Span reverse component (total correct trials) over 6 months (24 weeks) of treatment. [Time frame: Baseline to 6 months (end of treatment)]
• Change in Digit Span reverse component (total correct trials) over 9 months (36 weeks). [Time frame: Baseline to 9 months (3 months after end of treatment)]
• Change in Digit Symbol Substitution Test score over 6 months (24 weeks) of treatment. [Time frame: Baseline to 6 months (end of treatment)]

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 2 centers

• Stanford University — Palo Alto
• University of California San Francisco — San Francisco

Publications

• 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 A PMID 37085880

Identifiers

NCT: NCT05362292 · 21-35858 · 1R01AG075471-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗