Treatment of Incontinence Without Memory Problems (TRIUMPH)

An 8-week randomized, controlled, pilot clinical trial of Mirabegron compared to a standard anticholinergic therapy (Detrol LA) in elderly women with urgency urinary incontinence.

Study Overview

• Status: Completed
• Conditions: Urge Incontinence; Urinary Incontinence, Urge
• Intervention / Treatment: Drug: Mirabegron; Drug: Tolterodine Tartrate

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Community-dwelling, ambulatory females ≥ 65 years old
• Urgency or Mixed Urgency Predominate Urinary Incontinence (subject-reported) for ≥ 3 months prior to Screening (Visit 1)
• On a 3-day voiding diary, documentation of at least 3 urgency incontinence episodes with the number of urgency incontinence episodes greater than number of stress incontinence episodes
• Capability of understanding and having signed the informed consent form after full discussion of the research nature of the treatment and its risk and benefits
• Ability to perform all procedures and tests required by the protocol
• Report having a primary health care provider
• Willingness to remain on stable medication regime for duration of the randomized controlled trial. Participants will be asked to not add new medications during the randomized controlled trial, such as diuretics and other medications which may affect their voiding pattern.

Exclusion Criteria:

• Seated blood pressure >180/110 at Screening or Baseline
• Physician diagnosis of dementia
• Current use of dementia medications, debilitating or recent neurologic disease
• Mini Mental State Examination (MMSE) score <20
• History of urinary retention, gastric retention, uncontrolled narrow angle glaucoma, myasthenia gravis, severe ulcerative colitis, toxic megacolon, fistula or a hole in your bladder or rectum, birth defect leading to urine leakage, and urine leakage starting in childhood
• Clinically significant hepatic (Child Pugh B or greater) or renal (creatinin clearance <30 mL/min or eGFR <30 mL/min/1.73 m2)
• Neurologic conditions such as stroke, multiple sclerosis, spinal cord injury, or Parkinson's disease.
• Major cardiovascular even in the past 6 months (i.e., MI, unstable angina, hospitalization for chest pain)
• Symptomatic pelvic organ prolapse defined as participant report of feeling or seeing a bulge outside the vagina within the past 3 months.
• History of surgery for incontinence in the past 5 years, pelvic surgery the past 6 months (i.e., for prolapse or hysterectomy), intra-vesical therapy (botox), and/or bulk injections within the past 6 months.
• A known history of interstitial cystitis or a significant pain component associated with OAB symptoms, uninvestigated hematuria, urogenital cancer, radiation to the pelvis or external genitalia.
• Urinary tract infection (UTI) as shown by the results of the urinalysis at screening or recurrent urinary tract infection (RUTIs) defined as treatment for UTI >3 times in the last year.
• Urinary retention (post-void residual urine volume >150 cc measured by Bladder scan at screening.
• Use of any electrostimulation, bladder training, or pelvic floor exercises (with certified incontinence practitioners) within 4 weeks of Screening.
• Received study medication in any previous mirabegron clinical trial.
• Prior failure for either efficacy or tolerability of ≥ 2 OAB medications in the last year. (Failure: inadequate symptom control after two medications for a minimum of one month each.)

• Has been treated within 2 weeks prior to Screening and/or is currently being treated with:

  • Any drug treatment for OAB
  • Any drugs with significant anticholinergic and antispasmodic effects (see exception for tricyclic antidepressants below)
• Has started treatment with tricyclic antidepressants or estrogens within 4 weeks prior to Screening and/or is not on a stable dose.
• Intermittent use or unstable dose of diuretics. Treatment with diuretics initiated within 2 weeks prior to baseline and/or is not on a stable dose is not permitted.
• Treatment with potent CYP3A4 inhibitors, such as clarithromycin, ketoconazole, and itraconazole within 2 weeks prior to Screening.
• Administration of medications capable of inducing hepatic enzyme metabolism or transport (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John's Wort) in the past 30 days.
• Administration of narrow therapeutic index drugs metabolized by CYP2D6, such as thioridazine, flecainide, and propafenone.
• Previously received any investigational drug within 30 days prior to trial entry.
• Alcohol and/or any other drug abuse in the opinion of the investigator.
• Participants who have any medical (including known history of major hematological, renal, cardiovascular, or hepatic abnormalities) or psychological condition or social circumstances that would impair their ability to participate reliably in the trial, or those who may increase the risk to themselves or others by participating.
• Participants who, in the opinion of the investigator, are not likely to complete the trial for whatever reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Mirabegron; Participants will be instructed to take one tablet and 1 capsule (total of 2) of blinded study medication once a day, orally, for 8 weeks. They will start with Mirabegron (25mg) dose of study medication and will have the option of dose escalation to 2 tablets and 2 capsules (total of 4) per day (Mirabegron 50mg).	Drug: Mirabegron; Other Names: Myrbetriq
ACTIVE_COMPARATOR: Tolterodine Tartrate; Participants will be instructed to take one tablet and 1 capsule (total of 2) of blinded study medication once a day, orally, for 8 weeks. They will start with tolterodine tartrate (4 mg) dose of study medication and will have the option of dose escalation to 2 tablets and 2 capsules (total of 4) per day tolterodine tartrate 4 mg + identical placebo.	Drug: Tolterodine Tartrate; Other Names: Detrol LA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants Who Completed and Discontinued the Study	Feasibility - Assessment of retention rates.	Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in California Verbal Learning Test (CVLT) Score at 8 Weeks	Range of 0-80, with the higher the score the better.	Baseline to Week 8
Change From Baseline in Trail Making Test, Trail A Score at 8 Weeks	Trail Making Test, Trail A Time, Range 0-150 seconds, Lower score indicates better functioning	Baseline and 8 weeks
Change From Baseline in Short Physical Performance Battery (SPPB) Score at 8 Weeks	Physical function/mobility, Range 0-12, the higher the score the better.	Baseline to Week 8
Change From Baseline in Total Urinary Incontinence Frequency Measured by a Voiding Diary at 8 Weeks	Study participants record number of urinary incontinence episodes in a voiding diary. The total urinary incontinence frequency is the sum of urinary incontinence episodes per day.	Baseline to Week 8
Change From Baseline in Urge Incontinence Episodes Per Day on a Voiding Diary at 8 Weeks.	The sum of urge type incontinence episodes reported by participants on a voiding diary per day.	Baseline and 8 weeks

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Leslee Subak, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2016
• Primary Completion (ACTUAL): December 1, 2017
• Study Completion (ACTUAL): July 1, 2018

Study Registration Dates

• First Submitted: April 30, 2015
• First Submitted That Met QC Criteria: May 4, 2015
• First Posted (ESTIMATE): May 7, 2015

Study Record Updates

• Last Update Posted (ACTUAL): April 16, 2019
• Last Update Submitted That Met QC Criteria: March 28, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Urinary Incontinence; Urinary Incontinence, Urge; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Adrenergic beta-3 Receptor Agonists; Mirabegron; Tolterodine Tartrate
• Other Study ID Numbers: 14-15553