Sleep and Bladder Study

睡眠和膀胱研究

• 批准号: 10672228
• 负责人: Shachi Tyagi
• 金额: $ 47.41万
• 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/10672228
• 关键词: Address; Adherence; Adrenergic Receptor; Affect; Agonist; Anxiety; Anxiety Disorders; Attention; 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; Modeling; Muscarinics; 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 based; brain pathway; cognitive task; cost; design; disabling symptom; evidence base; executive function; holistic approach; human old age (65+); improved; improved outcome; improvement on sleep; incontinence symptom; insight; lower urinary tract symptoms; medication compliance; micturition urgency; multiple chronic conditions; neural; novel; novel therapeutics; older women; poor sleep; post intervention; primary endpoint; primary outcome; 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.

项目摘要 普遍的、病态的和昂贵的（≥ 830亿美元/年），急迫性尿失禁（UUI）是一个主要问题， 尤其是对老年妇女来说。病因通常归因于膀胱痉挛，可用的治疗方法有 以膀胱为目标，只提供适度的好处。尽管反应不足，依从性差， 几十年来，UUI的治疗方法几乎没有变化， 或加强目前的治疗将对那些有衰弱症状的人的护理产生重大影响。 UUI与睡眠不良有很强的双向关系，睡眠不良是老年人普遍的抱怨。高达50%的 老年人报告睡眠不好，这会使UUI的风险在5年内增加55%。大脑扮演着 在睡眠机制和睡眠中的重要作用是已知的，影响参与执行的途径。 控制系统。具体来说，睡眠不足与内侧前额叶皮层的活动减退有关 （mPFC）-我们已经确定参与排尿的执行控制的区域， 对生物反馈辅助盆底肌肉治疗的反应。因此，我们假设睡眠不好会抑制 膀胱控制，因为它与认知任务;和解决睡眠将改善执行控制的 膀胱补充同时膀胱靶向UUI治疗。 我们的总体目标是：（a）评估行为睡眠干预对UUI的额外益处， 标准治疗（β3-肾上腺素受体激动剂mirabegron），为评估和解决 睡眠治疗UUI，和（B）更好地了解大脑在睡眠对UU提供的影响中的作用 研究针对所识别的脑通路的其他基于脑的改善疗法的基本原理。 具体目的是检查连续性短暂行为治疗的效果， 一线药物治疗：米拉贝隆（1）UUI;（2）尿激酶;（3）mPFC活性，以确认治疗 通过评估睡眠对目前理解的介质的影响来评估机制;以及（4） 治疗反应。 我们将随机分配100名年龄≥ 60岁的女性，接受8周的米拉贝隆单药治疗或 米拉贝隆+BBTI，评估膀胱症状，睡眠，以及术前和术后的功能和结构性脑变化 干预后。我们还将探讨干预后6个月治疗反应的持久性。 这项研究将提供有史以来第一个全面的多组分脑膀胱治疗的数据， 失禁靶向已知的大脑机制涉及控制失禁。它将评估临床 这种新型配对的反应和持久性，并提供了相关的潜在途径的理解 在其治疗机制。