Sleep and Bladder Study

睡眠和膀胱研究

• 批准号: 10419943
• 负责人: Shachi Tyagi
• 金额: $ 44.95万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10419943
• 关键词: Address; Adherence; Adrenergic Receptor; Affect; Agonist; Anxiety; Attention; Base of the Brain; Behavior Therapy; Behavioral; Biofeedback; Bladder; Bladder Control; Brain; Caring; Clinical; Combined Modality Therapy; Comorbid Insomnia; Complement; Complex; Data; Development; Disease; Elderly; Etiology; Frequencies; Goals; Hour; Impairment; Incontinence; Intervention; Knowledge; Link; Medial; Mediating; Mediator of activation protein; Modeling; Nocturia; Overactive Bladder; Pathway interactions; Patients; Pelvic Floor Muscle; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Play; Prefrontal Cortex; Quality of life; Randomized; Randomized Controlled Trials; Reporting; Risk; Role; Secondary to; Sleep; Sleep Deprivation; Sleep disturbances; Sleeplessness; Spasm; Symptoms; Therapeutic; Urinary Incontinence; Woman; adherence rate; aged; attentional control; brain pathway; cognitive task; cost; design; disabling symptom; evidence base; executive function; holistic approach; human old age (65+); improved; improved outcome; incontinence symptom; insight; lower urinary tract symptoms; medication compliance; micturition urgency; multiple chronic conditions; novel; novel therapeutics; older women; poor sleep; post intervention; primary endpoint; primary outcome; relating to nervous system; response; side effect; standard of care; success; targeted treatment; treatment effect; treatment response

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.

项目总结