Nighttime Agitation and Restless Legs Syndrome in People with Alzheimer's Disease

阿尔茨海默病患者的夜间躁动和不宁腿综合症

• 批准号: 9391501
• 负责人: CHRISTINE R KOVACH
• 金额: $ 80.71万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9391501
• 关键词: Nighttime; Agitation; Restless; Legs; Syndrome

 DESCRIPTION (provided by applicant): Nighttime agitation and sleep disturbance in persons with dementia (PWD) causes patient suffering, may accelerate cognitive decline, leads to burdened caregivers, and is costly to manage. Pharmacological interventions are primarily antipsychotics and hypnotics. Effectiveness is unconvincing, and these drugs are associated with falls, strokes, and death. There is a lack of tailored, effective, and sustainable treatments for nighttime agitation and sleep disturbance in PWD. Our approach to this problem is innovative because, unlike pharmacological interventions in the past, it tailors the intervention t a treatable condition, restless legs syndrome (RLS), which may be causing the nighttime agitation and sleep disturbance. In our previous research we showed that about 24% of PWD have an undiagnosed sleep disorder, RLS; that RLS was associated with nighttime agitation and sleep disturbance in PWD; and we developed and validated an RLS diagnostic and outcome measure suitable for PWD. In order for our work to significantly impact standards of clinical practice, evidence is needed on whether RLS behaviors cause nighttime agitation, and if treating RLS behaviors reduces or stops nighttime agitation and improves sleep in PWD. We have chosen gabapentin encarbil (GEn), as the RLS treatment in this research because it is FDA approved for RLS and has a favorable safety profile. We propose an 8-week, double-blind placebo-controlled randomized clinical trial of GEn versus placebo in 120 nursing home residents with nighttime agitation, sleep disturbance, and RLS. The specific aims of this pilot study are to: 1) Determine the effect of GEn, compared to placebo on nighttime agitation (primary endpoint) in PWD with RLS. We hypothesize that compared to the placebo control group, the treatment group will have fewer nighttime agitation behaviors. 2) Describe the safety profile of GEn compared to placebo in this population. 3) Estimate the effect size of GEn compared to placebo on nighttime sleep and RLS behaviors. We hypothesize that compared to the placebo control group, the treatment group will have better nighttime sleep and fewer RLS behaviors. 4) Explore whether frequency of RLS behaviors is a causal mechanism for nighttime agitation. We hypothesize that frequency of RLS behaviors will mediate the effect of GEn on nighttime agitation behaviors. The results of this study and future definitive trials have the potential to radically shift and drastically improve standards of clinical practice for assessment and treatment of three highly prevalent, often comorbid conditions in PWD: RLS, nighttime agitation, and sleep disturbance. For scientists, our results may provide insight into the mechanism for nighttime agitation and sleep disturbance in PWD and inform future research. For PWD, our findings may result in less nighttime agitation and discomfort from RLS, improved nighttime sleep, and improved sleep may enhance daytime cognitive functioning and quality of life. Application of our findings into the home setting may result in fewer nursing home admissions for PWD and less caregiver burden because the PWD (and their caregivers) can get more sleep.

 描述（由申请人提供）：痴呆症（PWD）患者的夜间躁动和睡眠障碍导致患者痛苦，可能加速认知能力下降，导致护理人员负担沉重，并且管理成本高昂。药物干预主要是抗精神病药和催眠药。有效性不令人信服，这些药物与福尔斯、中风和死亡有关。对于PWD患者的夜间躁动和睡眠障碍，缺乏定制的，有效的和可持续的治疗方法。我们解决这个问题的方法是创新的，因为与过去的药物干预不同，它针对可治疗的疾病，不宁腿综合征（RLS）进行了干预，这可能会导致夜间躁动和睡眠障碍。在我们之前的研究中，我们发现大约24%的PWD患有未诊断的睡眠障碍，RLS; RLS与PWD的夜间躁动和睡眠障碍相关;我们开发并验证了适合PWD的RLS诊断和结局测量。为了使我们的工作能够显著影响临床实践的标准，需要证据来证明RLS行为是否会导致夜间躁动，以及治疗RLS行为是否会减少或停止夜间躁动并改善PWD的睡眠。我们选择加巴喷丁恩卡比（GEn）作为本研究中的RLS治疗，因为它是FDA批准的RLS，具有良好的安全性。我们提出了一个为期8周，双盲安慰剂对照的随机临床试验GEn与安慰剂在120名疗养院居民夜间躁动，睡眠障碍，RLS。本初步研究的具体目的是：1）确定GEn与安慰剂相比对伴有RLS的PWD患者夜间激越（主要终点）的影响。我们假设，与安慰剂对照组相比，治疗组将有更少的夜间躁动行为。2)描述GEn与安慰剂相比在该人群中的安全性特征。3)估计GEn与安慰剂相比对夜间睡眠和RLS行为的效应量。我们假设，与安慰剂对照组相比，治疗组将有更好的夜间睡眠和更少的RLS行为。4)探索RLS行为的频率是否是夜间躁动的因果机制。我们假设RLS行为的频率将介导GEn对夜间激越行为的影响。这项研究的结果和未来的确定性试验有可能从根本上改变和大幅提高临床实践的标准，以评估和治疗PWD中三种高度流行的，经常合并的疾病：RLS，夜间躁动和睡眠障碍。对于科学家来说，我们的研究结果可以深入了解PWD夜间激动和睡眠障碍的机制，并为未来的研究提供信息。对于PWD，我们的研究结果可能会减少RLS引起的夜间躁动和不适，改善夜间睡眠，改善睡眠可能会提高白天的认知功能和生活质量。将我们的研究结果应用到家庭环境中可能会减少PWD的疗养院入院率，减轻护理人员的负担，因为PWD（及其护理人员）可以获得更多的睡眠。