Clinical trial NCT05880862: Comparative Effectiveness of Initial OAB Treatment Options Among Older Women at High Risk of Falls
Official title: Comparative Effectiveness of Pelvic Floor Muscle Training, Mirabegron, and Trospium Among Older Women With Urgency Urinary Incontinence and High Fall Risk: a Feasibility Randomized Clinical Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Urinary Bladder, Overactive
Urinary Incontinence
Accidental Falls
Keywords: OAB
Falls
Older adults
Urinary incontinence
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2023-05-30
Enrollment: 48
Sex: FEMALE
Minimum age (years): 60
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a pilot, multi-arm, mixed methods, randomized clinical study.
Primary purpose: TREATMENT

Brief summary: The goal of this study is to conduct a randomized pilot multi-arm clinical trial comparing a standard course of physical therapist provided pelvic floor muscle training (PFMT) to pharmacologic therapy for the treatment of urgency urinary incontinence (UUI) or Overactive Bladder (OAB) in older women at high risk of falling.

The central hypotheses for this project are i) a randomized pilot multi-arm clinical trial comparing PFMT to drug treatment for UUI or OAB in older women at high risk of falling is feasible; and ii) treatment approach can influence both UI and fall related outcomes in this patient population.

The main questions it aims to answer are: 1) Is a multi-arm clinical trial comparing PFMT to drug treatment for UUI or OAB in older women at high risk of falling feasible? and 2) How does treatment approach influence both OAB and fall related outcomes in this patient population?

Women (16 per arm) 60 years and older with UUI or OAB who screen positive for high fall risk will be randomized to one of three standard of care treatment arms and followed for six months. The three treatment arms are i) a 12-week structured behaviorally based pelvic floor muscle training (PFMT) intervention administered by physical therapists in the clinic; ii) a 12-week course of the beta-3 agonist, Mirabegron; and iii) a 12-week course of the antimuscarinic, Trospium Chloride. Researchers will compare study feasibility and OAB symptom related outcomes across the three groups to see if a larger clinical trial is warranted.

Detailed description: Untreated, urinary urgency and incontinence can precipitate a vicious cycle of decreasing physical activity, social isolation, fear-of-falling, and falls. The urge to urinate frequently can also limit physical activity - concern for finding oneself too far from a bathroom can be a powerful motivator for just staying home. Structured behavioral interventions or medications are common initial treatment options. But they elicit their effects through very different mechanisms of action that may influence fall related outcomes differently. There is, however, a critical lack of direct head-to-head trial evidence on non-pharmacologic and pharmacologic treatments for urgency urinary incontinence (UUI), particularly in women with co-existing fall risk. The proposed feasibility pilot study is a randomized, multi-arm, mixed methods, clinical trial comparing three currently in use initial treatment options for older women: i) a 12-week structured behaviorally based pelvic floor muscle training (PFMT) intervention administered by physical therapists in the clinic; ii) a 12-week course of the beta-3 agonist, Mirabegron; and iii) a 12-week course of the antimuscarinic, Trospium Chloride, in women 60 and older with UUI or overactive bladder (OAB) who also screen positive for increased risk of falling. Mirabegron and Trospium are not associated with longitudinal effects on cognition that the traditionally used anticholinergic mediations have recently been linked to. The Specific Aims are 1) Conduct a pilot study in clinical settings to determine the feasibility of enrolling older women with UUI or OAB who are at high risk of falling in a three-arm (PFMT, vs. mirabegron vs. Trospium), randomized comparative effectiveness trial; 2) Characterize outcomes across the three interventions; and 3) Qualitatively explore perceived factors influencing the non-pharmacologic and pharmacologic treatment experience in these patients. Forty-eight ambulatory women (16 per arm) 60 years and older with UUI or OAB and who screen positive for high fall risk will be randomized (1:1:1) to one of three arms. Feasibility will be determined through key milestones on evaluability, adherence to the interventions, attrition, adverse events, productive recruitment methods, and sample characteristics. The Investigators will also measure important indicators of symptom severity, quality of life, physical activity, falls, and fear of falling. Building upon our preliminary work, fall risk will be determined by the Centers for Disease Control and Prevention (CDC), Stopping Elderly Accidents, Deaths, and Injuries (STEADI) fall risk screening tool. The proposed study is the first to compare these common non-surgical treatments for UUI and OAB in a high fall risk patient population and will lay the groundwork for a program of research investigating the bidirectional relationships that exist across these two common geriatric syndromes both at the level of shared risk factors and response to treatment.

Eligibility criteria: Inclusion Criteria:

1. Women aged 60 year or older.
2. Ambulatory (able to walk across a small room with or without an assistive device).
3. Urgency UI, OAB, or Mixed UI (both urgency and stress UI) as identified by study physicians.
4. Answered "yes" to one of the items on the 3-Key Questions, questionnaire.
5. A score of 6 or greater on the International Consultation on Incontinence Modular Questionnaire - Overactive Bladder (ICIQ-OAB) instrument or a physician recommended treatment.
6. Able to provide one's own informed consent.
7. Has tried basic lifestyle modifications for her bladder condition.
8. Has Medicare or private insurance

Exclusion Criteria:

1. Male (their causes of urinary incontinence are often different from women)
2. Unstable psychiatric conditions (e.g., psychosis, suicidal) based on history and medical records.
3. Nursing home resident
4. Genitourinary cancer undergoing active treatment with chemotherapy or radiation.
5. Neurologic conditions known to contribute to incontinence (Multiple Sclerosis, Parkinson's Disease, Traumatic Brain Injury, Dementia, and Stroke Survivors with limited mobility)
6. New OAB treatments planned during the 6-month study duration - includes medications and/or surgery.
7. History of surgically implanted sacral nerve stimulator or botulinum toxin bladder injections for UI.
8. Taking other antimuscarinic drugs or Digoxin
9. Severe uncontrolled hypertension
10. Diagnosed Glaucoma
11. Myasthenia gravis
12. Chronic liver or kidney diseases

Primary outcomes:
measure: Evaluability
timeFrame: Assessed at the end of the 12-week intervention period
measure: Clinical-Based Adherence
timeFrame: Assessed at the end of the 12-week intervention period
measure: Home-Based Adherence
timeFrame: Assessed at the end of the 12-week intervention period
measure: Medication Adherence
timeFrame: Assessed at the end of the 12-week intervention period
Secondary outcomes:
measure: International Consultation on Incontinence Modular Questionnaire - Overactive Bladder (ICIQ-OAB)
timeFrame: Baseline; at the end of the 12-week intervention; and at the 6-month follow-up.
measure: International Consultation on Incontinence Questionnaire Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol)
timeFrame: Baseline; at the end of the 12-week intervention; and at the 6-month follow-up.
measure: Falls Efficacy Scale International (FES-I)
timeFrame: Baseline; at the end of the 12-week intervention; and at the 6-month follow-up.
measure: Number of Participants with Incident falls
timeFrame: Baseline; at the end of the 12-week intervention; and at the 6-month follow-up.
measure: PROMIS Satisfaction with Participation in Social Roles
timeFrame: Baseline; at the end of the 12-week intervention; and at the 6-month follow-up.
measure: Short Physical Performance Battery (SPPB)
timeFrame: Baseline; at the end of the 12-week intervention; and at the 6-month follow-up.
measure: Physical activity
timeFrame: The accelerometer will be worn for 1 week after randomization; for 1 week at the end of the 12-week intervention; and for 1 week at the 6-month follow-up.
measure: PROMIS physical functioning 8b
timeFrame: Baseline; at the end of the 12-week intervention; and at the 6-month follow-up.
measure: Absorbent pad use
timeFrame: Baseline; at the end of the 12-week intervention; and at the 6-month follow-up.
Other outcomes:
measure: Qualitative interviews
timeFrame: Baseline; at the end of the 12-week intervention; and at the 6-month follow-up.
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston
state: Texas
Study officials:
affiliation: University of Texas Medical Branch at Galveston
name: Steve Fisher
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brown JS, Vittinghoff E, Wyman JF, Stone KL, Nevitt MC, Ensrud KE, Grady D. Urinary incontinence: does it increase risk for falls and fractures? Study of Osteoporotic Fractures Research Group. J Am Geriatr Soc. 2000 Jul;48(7):721-5. doi: 10.1111/j.1532-5415.2000.tb04744.x.
citation: Chiarelli PE, Mackenzie LA, Osmotherly PG. Urinary incontinence is associated with an increase in falls: a systematic review. Aust J Physiother. 2009;55(2):89-95. doi: 10.1016/s0004-9514(09)70038-8.
citation: Foley AL, Loharuka S, Barrett JA, Mathews R, Williams K, McGrother CW, Roe BH. Association between the Geriatric Giants of urinary incontinence and falls in older people using data from the Leicestershire MRC Incontinence Study. Age Ageing. 2012 Jan;41(1):35-40. doi: 10.1093/ageing/afr125. Epub 2011 Sep 24.
citation: Balk E, Adam GP, Kimmel H, Rofeberg V, Saeed I, Jeppson P, Trikalinos T. Nonsurgical Treatments for Urinary Incontinence in Women: A Systematic Review Update [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Aug. Report No.: AHRQ 18-EHC016-EFReport No.: PCORI(R) 2018-SR-03. Available from http://www.ncbi.nlm.nih.gov/books/NBK534625/
citation: Gibson W, Hunter KF, Camicioli R, Booth J, Skelton DA, Dumoulin C, Paul L, Wagg A. The association between lower urinary tract symptoms and falls: Forming a theoretical model for a research agenda. Neurourol Urodyn. 2018 Jan;37(1):501-509. doi: 10.1002/nau.23295. Epub 2017 May 4.
citation: Fisher SR, Harmouche I, Kilic GS. Prevalence and Predictors of Increased Fall Risk Among Women Presenting to an Outpatient Urogynecology and Pelvic Health Center. Female Pelvic Med Reconstr Surg. 2022 Feb 1;28(2):e7-e10. doi: 10.1097/SPV.0000000000001118.