What is the mechanism of action of this treatment?

The most common treatments for Urge Incontinence include anticholinergic agents and beta-3-adrenergic agonists. Anticholinergic agents block acetylcholine receptors in the bladder, reducing involuntary bladder contractions and increasing bladder capacity, which helps control the sudden urge to urinate. Beta-3-adrenergic agonists relax the bladder muscle by stimulating beta-3 adrenergic receptors, also increasing bladder capacity and reducing urgency. These mechanisms are crucial for managing symptoms and improving the quality of life for Urge Incontinence patients.

What side effects are associated with this type of intervention?

Anticholinergic bladder therapies, such as oxybutynin, tolterodine, and solifenacin, are commonly used to treat urge incontinence by blocking acetylcholine receptors to reduce bladder contractions. Common side effects of these medications include dry mouth, constipation, blurred vision, dizziness, and cognitive dysfunction, particularly in older adults. Extended-release formulations tend to have fewer side effects compared to immediate-release versions. Additionally, these medications are contraindicated in patients with certain conditions like gastric retention and angle-closure glaucoma.

What prior FDA approvals exist?

The FDA has approved several anticholinergic drugs for the treatment of urge incontinence, which work by blocking acetylcholine receptors to reduce bladder contractions. Notable examples include oxybutynin, tolterodine, solifenacin, darifenacin, fesoterodine, and trospium. These medications help manage symptoms by relaxing the bladder muscle, thereby reducing the urgency and frequency of urination.

What other types of research exist?

Promising novel alternatives to anticholinergic bladder therapy for urge incontinence include: <ol> <li>Beta-3-adrenergic agonists (e.g., Mirabegron) - These medications relax the bladder muscle, increasing its storage capacity and reducing the urgency to urinate.</li> <li></li> </ol> Percutaneous Tibial Nerve Stimulation (PTNS) - A minimally invasive procedure that stimulates the tibial nerve to improve bladder control. 3. Intravesical Botulinum Toxin A Injections - These injections can reduce bladder muscle overactivity and are particularly useful for patients who do not respond to oral medications. 4. Sacral Neuromodulation - A surgical option that involves implanting a device to stimulate the sacral nerves, which control bladder function.

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Beta-3 Adrenergic Agonist

Bladder Therapy for Urinary Incontinence (TRIUMPH Trial)

Phase 4

Recruiting

Led By Alison Huang, MD, MAS, MPhil

Research Sponsored by University of California, San Francisco

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Report 2 or more urgency incontinence episodes over a 7-day period

Female sex at birth, without surgical or hormonal gender re-assignment therapy

Must not have

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

Severe hepatic impairment (Child-Pugh score B or greater) or renal impairment (creatinine clearance <30 mL/min) as a contraindication to both study medications

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to 9 months (3 months after end of treatment)

Awards & highlights

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial is testing two types of bladder medications in older women with bladder control issues. One medication blocks signals to the bladder, and the other helps the bladder hold more urine. The goal is to see which treatment works best and how they affect overall function.

Who is the study for?

The TRIUMPH study is for ambulatory older women aged 60 or above with urgency-predominant urinary incontinence and normal to mildly impaired cognitive function. Participants must have experienced urinary incontinence for at least 3 months, with episodes of sudden urgency, and be able to use the toilet without help. Exclusions include dementia diagnosis, recent medication changes affecting cognition or urination, severe liver/renal impairment, UTI, certain medical conditions like uncontrolled glaucoma or myasthenia gravis.

What is being tested?

This trial compares two medications—Tolterodine Tartrate ER (an anticholinergic) and Mirabegron (a beta-3-adrenergic agonist)—against a placebo to see their effects on cognitive and urinary functions in older women with overactive bladders. It's a randomized double-blind study where participants won't know which treatment they're getting.

What are the potential side effects?

Potential side effects may include dry mouth, constipation (from Tolterodine), increased blood pressure, headaches (from Mirabegron), and general discomfort from taking the medications. The exact side effects will vary by individual.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have had at least 2 sudden urges to urinate that I couldn't control in the last week.

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I was born female and have not undergone gender re-assignment.

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I can walk to the bathroom and use it by myself.

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I am 60 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't taken any medication in the last month that could badly interact with the study drugs.

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I do not have severe liver or kidney problems.

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My blood pressure is not higher than 180/110 mmHg.

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I am experiencing difficulty emptying my bladder fully.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to 9 months (3 months after end of treatment)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to 9 months (3 months after end of treatment)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to 9 months (3 months after end of treatment) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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.

Secondary study objectives

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

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

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

+42 more

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Active Control

Placebo Group

Group I: Anticholinergic bladder medication plus behavioral self-management educationActive Control1 Intervention

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.

Group II: Beta-3-adrenergic agonist medication plus behavioral self-management educationActive Control1 Intervention

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.

Group III: Placebo medication plus behavioral self-management educationPlacebo Group1 Intervention

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.

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Urge Incontinence include anticholinergic agents and beta-3-adrenergic agonists. Anticholinergic agents block acetylcholine receptors in the bladder, reducing involuntary bladder contractions and increasing bladder capacity, which helps control the sudden urge to urinate. Beta-3-adrenergic agonists relax the bladder muscle by stimulating beta-3 adrenergic receptors, also increasing bladder capacity and reducing urgency. These mechanisms are crucial for managing symptoms and improving the quality of life for Urge Incontinence patients.

Antimuscarinic agents: implications and concerns in the management of overactive bladder in the elderly.