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Principal Investigator: Shachi Tyagi
Organization: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Fiscal Year: 2024
Award: $456,832
Funding agency: National Institute on Aging
PROJECT SUMMARY
Prevalent, morbid, and costly (≥$83 billion/year), urgency urinary incontinence (UUI) is a major problem,
especially for older women. With etiology usually ascribed to bladder spasms, the available therapies are
bladder-targeted and provide only a modest benefit. Despite inadequate response and poor adherence, there
has been little change in therapeutic approach to UUI in decades, and a novel holistic approach to complement
or enhance current treatment will have a significant impact on care of those with the debilitating symptoms.
UUI has strong bidirectional relationship with poor sleep, a prevalent complaint in older adults. Up to 50% of
older adults report poor sleep, which increases the risk of UUI by up to 55% over 5 years. The brain plays a
vital role in the continence mechanism and sleep is known to affect the pathways involved in executive
continence control. Specifically, sleep loss is associated with hypoactivity in the medial prefrontal cortex
(mPFC) – a region we have identified to be involved in executive control of voiding, and potential therapeutic
response to biofeedback-assisted pelvic floor muscle therapy. Hence, we hypothesize that poor sleep inhibits
bladder control as it does with cognitive tasks; and addressing sleep will improve executive control of the
bladder complementing concurrent bladder-targeted UUI therapy.
Our overall goals are to: (a) assess the additional benefit of behavioral sleep intervention on UUI to the
standard of care (β3- adrenoceptor agonist mirabegron) providing evidence for assessing and addressing
sleep for treatment of UUI, and (b) better understand the brain’s role in the effect of sleep on UU providing
rationale to investigate other ameliorative brain-based therapies targeting the identified brain pathways.
Specific aims are to examine the effect of adjunctive Brief Behavioral Treatment of Insomnia (BBTI) with the
first-line pharmacotherapy: mirabegron on (1) UUI; (2) nocturia; (3) mPFC activity to confirm therapeutic
mechanisms by assessing the effect of sleep on currently understood mediators; and (4) durability of
therapeutic response.
We will randomize 100 women aged ≥ 60 years to receive 8 weeks of either mirabegron alone or
mirabegron+BBTI, assessing bladder symptoms, sleep, and functional and structural brain changes pre- and
post-intervention. We will also explore the durability of therapeutic response at 6-months post-intervention.
The study will provide the first-ever data on a comprehensive multicomponent brain-bladder therapy for
incontinence targeting the known brain mechanisms involve in continence control. It will evaluate clinical
response and durability of this novel pairing and provide an understanding of the underlying pathways involved
in its therapeutic mechanism.
Terms: <65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><Address><Adherence><Adrenergic Receptor><Adrenoceptors><Affect><Aged 65 and Over><Agonist><Anxiety><Anxiety Disorders><Attention><Behavior Conditioning Therapy><Behavior Modification><Behavior Therapy><Behavior Treatment><Behavioral Conditioning Therapy><Behavioral Modification><Behavioral Therapy><Behavioral Treatment><Biofeedback><Bladder><Bladder Control><Bladder Urinary System><Brain><Brain Nervous System><Caring><Causality><Clinical><Combined Modality Therapy><Comorbid Insomnia><Complement><Complement Proteins><Complex><Conditioning Therapy><Data><Development><Disease><Disorder><Drug Therapy><Drugs><Encephalon><Epinephrine Receptors><Etiology><Frequencies><Goals><Hour><Hyperkinesia><Hyperkinesis><Hyperkinetic Movements><Impairment><Incontinence><Insomnia><Insomnia Disorder><Intervention><Intervention Strategies><Knowledge><Link><Medial><Mediating><Mediator><Medication><Modeling><Multimodal Therapy><Multimodal Treatment><Muscarinic Agents><Muscarinics><Muscle Spasm><Muscular Spasm><Nocturia><Nycturia><Older Population><Overactive Bladder><Pathway interactions><Patients><Pelvic Floor Muscle><Peripheral><Pharmaceutical Preparations><Pharmacotherapy><Play><Prefrontal Cortex><QOL><Quality of life><Randomized><Randomized, Controlled Trials><Reporting><Risk><Role><Secondary to><Sleep><Sleep Deprivation><Sleep disturbances><Sleeplessness><Spasm><Symptoms><Therapeutic><Urgency to pass urine><Urgent desire to urinate><Urinary Incontinence><Woman><aberrant sleep><above age 65><adenoreceptor><adherence rate><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age of 65 years onward><aged><aged 65 and greater><aged 65+><aged ≥65><attentional control><behavior intervention><behavioral intervention><behavioral sleep health intervention><behavioral sleep health program><behavioral sleep intervention><behavioral sleep strategies><behavioral sleep therapy><behavioral sleep treatment><bladder continence><brain based><brain pathway><causation><co-morbid insomnia><cognitive task><combination therapy><combined modality treatment><combined treatment><complementation><cost><debilitating symptom><deficient sleep><design><designing><developmental><disease causation><disrupted sleep><disturbed sleep><drug adherence><drug compliance><drug treatment><drug/agent><evidence base><executive control><executive function><holistic approach><human old age (65+)><impaired sleep><improved><improved outcome><improvement on sleep><inadequate sleep><incontinence symptom><insight><insufficient sleep><interventional strategy><irregular sleep><lower urinary tract symptoms><medication adherence><medication compliance><micturition control><micturition urgency><multi-modal therapy><multi-modal treatment><multimorbidity><multiple chronic conditions><neural><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><old age><older adult><older adulthood><older groups><older individuals><older person><older women><over 65 years><pathway><poor sleep><post intervention><primary end point><primary endpoint><primary outcome><randomisation><randomization><randomized control trial><randomly assigned><response><response to therapy><response to treatment><side effect><sleep debt><sleep deficiency><sleep deficit><sleep disruption><sleep dysregulation><sleep improvement><sleep insufficiency><sleep loss><social role><standard of care><success><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic response><therapy response><treatment effect><treatment response><treatment responsiveness><urinary bladder><urinary continence><urinary control><urinary urgency><urination control><urination urgency><≥65 years>