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: 9886167
• 负责人: Kathy Culpepper Richards
• 金额: $ 75.18万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9886167
• 关键词: Address; Adverse event; Aggressive behavior; Agitation; Alzheimer' s Disease; Anemia; Antidepressive Agents; Antipsychotic Agents; Apnea; Appearance; Bed rest; Behavior; Behavioral; Caregiver Burden; Caregivers; Caring; Cessation of life; Circadian Rhythms; Clinical Trials; Cognition; Complex; Consensus; Control Groups; Data; Dementia; Diagnosis; Diagnostic Procedure; Distress; Double-Blind Method; Effectiveness; Elderly; Environment; Esthesia; Etiology; Evaluation; Fatigue; Frequencies; Future; Hour; Institutionalized Persons; Intervention; Interview; Iron; Knowledge; Leg; Light; Measures; Mediating; Medical History; Methods; Moods; Movement; Neurodegenerative Disorders; Nursing Homes; Obstructive Sleep Apnea; Patients; Pattern; Periodicity; Persons; Pharmaceutical Preparations; Pharmacology; Pilot Projects; Placebo Control; Placebos; Polysomnography; Population; Prevalence; Provider; Quality of life; Randomized; Reporting; Research; Restless Legs Syndrome; Safety; Sensory; Sleep; Sleep Disorders; Sleep disturbances; Stroke; Symptoms; Testing; Training; Treatment Failure; United States Food and Drug Administration; Work; arm; circadian; clinical practice; cognitive skill; community setting; cost; dementia care; effective therapy; fall risk; falls; follow-up; gabapentin; improved; multiple data sources; patient population; personalized approach; pilot trial; precision medicine; primary endpoint; randomized placebo-controlled clinical trial; safety assessment; safety outcomes; side effect; statistics; suprachiasmatic nucleus; tool; treatment group

Project Summary/Abstract. Nighttime agitation, defined as the appearance or exacerbation of behavioral disturbances, such as wandering and aggression, in the afternoon and/or evening, is a prevalent symptom in persons with Alzheimer’s disease that reduces their quality of life and restricts their environments. Effective treatments are lacking. One major cause for past failure of treatments has been the approach of treating all nighttime agitation alike. Unlike interventions in the past, our precision medicine approach tailors the intervention to a specific sleep disorder, restless legs syndrome (RLS). RLS occurs in 10-14% of older adults and it is likely that persons with Alzheimer’s disease have RLS, since it is quite common, but it is infrequently identified because diagnosis is dependent on patients answering complex questions about their symptoms. RLS causes an urge to move associated with uncomfortable and unpleasant leg sensations. The urge to move and leg discomfort only occur or worsen at night, and relief is by movement. We hypothesized that RLS might be an etiology for nighttime agitation because: 1) circadian patterns of nighttime agitation and RLS symptoms are almost identical; 2) unrelieved RLS discomfort may precipitate behaviors such as screaming and requests for help, and the urge to move may cause wandering, pacing, and restlessness; and 3) factors common in institutionalized persons with Alzheimer’s disease, such as anemia, prolonged bed rest, and antidepressants, trigger or worsen RLS. Our preliminary work supports our hypothesis, and provides beginning evidence that RLS may be an unidentified etiology for nighttime agitation. In 59 persons with dementia and nighttime agitation, and RLS diagnosed using objective measures, we found that almost ¼ had RLS and that RLS was associated with nighttime agitation (r = 0.31, p .01). We now propose a pilot clinical trial to determine if RLS treatment reduces nighttime agitation, improves sleep, reduces antipsychotic medications, and the mechanism for these effects. We have chosen gabapentin enacarbil (GEn) as the treatment because it is FDA approved for RLS and has a favorable safety profile. We propose an 8-week, double-blind placebo-controlled randomized pilot trial of GEn versus placebo in 136 nursing home residents with moderate to severe Alzheimer’s disease, nighttime agitation, and RLS, followed by an 8-week post-trial evaluation of antipsychotic medication use. The specific aims are to: 1) Determine the effect of GEn, compared to placebo on nighttime agitation (primary endpoint); 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, RLS behaviors, and antipsychotic medications; 4) Explore whether frequency of RLS behaviors mediates the effect of GEn on nighttime agitation behaviors. The results of this study and future definitive trials may shift and improve standards of care for treatment of nighttime agitation; reduce elopement, aggression, and other nighttime agitation behaviors; and improve sleep.

项目摘要/摘要。夜间躁动，定义为出现或加重的行为 在下午和/或晚上的骚乱，如漫步和攻击性，是 阿尔茨海默病患者会降低他们的生活质量，限制他们的环境。有效 治疗手段匮乏。过去治疗失败的一个主要原因是治疗急性淋巴细胞白血病的方法 夜间的骚动也一样。与过去的干预不同，我们的精准医疗方法量身定做 干预一种特定的睡眠障碍，不宁腿综合症(RLS)。10%-14%的老年人会发生RLS 阿尔茨海默病患者很可能患有RLS，因为它很常见，但很少见 确定是因为诊断依赖于患者回答关于其症状的复杂问题。 RLS会引起与腿部不适和不适相关的运动冲动。搬家的冲动 腿部不适只有在晚上才会出现或恶化，缓解方法是运动。我们假设RLS可能 是夜间躁动的病因，因为：1)夜间躁动和RLS症状的昼夜节律模式 几乎相同；2)未缓解的RLS不适可能会引发尖叫和要求等行为 寻求帮助，而行动的冲动可能会导致走动、走动和不安；以及3)常见的 住院的阿尔茨海默病患者，如贫血、长时间卧床和抗抑郁药物， 触发或恶化RLS。我们的初步工作支持了我们的假设，并提供了初步证据 RLS可能是夜间躁动的一种不明原因。在59名痴呆症患者和夜间 激越，并使用客观测量诊断RLS，我们发现近1/4的人有RLS，而RLS是 与夜间躁动有关(r=0.31，P<0.01)。我们现在提议进行一项试点临床试验，以确定RLS 治疗减少夜间躁动，改善睡眠，减少抗精神病药物的使用，其机制是 对于这些影响。我们选择加巴喷丁奈卡比(GEN)作为治疗方法，因为它是FDA批准的 RLS，并具有良好的安全性。我们提出了一项为期8周的双盲安慰剂对照随机试验 在136名患有中重度阿尔茨海默病的疗养院居民中进行的Gen与安慰剂的试点试验， 夜间躁动和RLS，随后对抗精神病药物的使用进行为期8周的试验后评估。这个 具体目标是：1)确定GEN与安慰剂相比对夜间躁动的影响(主要 终点)；2)描述GEN与安慰剂在该人群中的安全性比较；3)评估其效果 Gen的大小与安慰剂在夜间睡眠、RLS行为和抗精神病药物方面的比较；4)探索 RLS行为频率是否在GEN对夜间激越行为的影响中起中介作用。结果是 这项研究和未来的最终试验可能会改变和提高夜间治疗的护理标准 激越；减少私奔、攻击性和其他夜间激越行为；改善睡眠。