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 (ß3- 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
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.