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

基本信息

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
项目类别：
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&apos 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

项目摘要

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，定义为行为的出现或加剧。下午和/或晚上的干扰，例如徘徊和攻击性，是以下人群的普遍症状患有阿尔茨海默病的人会降低他们的生活质量并限制他们的环境。缺乏治疗方法是过去治疗失败的一个主要原因。与过去的干预措施不同，我们的精准医疗方法针对的是夜间躁动。对一种特定的睡眠障碍——不宁腿综合征 (RLS) 进行干预，10-14% 的老年人会出现这种情况。患有阿尔茨海默病的人很可能患有不宁腿综合征，因为这种情况很常见，但很少见之所以能够确定，是因为诊断取决于患者回答有关其症状的复杂问题。不宁腿综合症会引起与不舒服和不愉快的腿部感觉相关的移动冲动。腿部不适仅在夜间发生或加重，通过运动可以缓解。我们发现 RLS 可能会缓解。成为夜间躁动的病因，因为：1) 夜间躁动和 RLS 症状的昼夜节律模式 2) 未缓解的不宁腿不适可能会引发尖叫和提出要求等行为寻求帮助，而想要移动的冲动可能会导致走神、踱步和不安；以及 3) 常见的因素；患有阿尔茨海默病的住院患者，如贫血、长期卧床和抗抑郁药物，我们的初步工作支持我们的假设，并提供了初步证据： 59 名患有痴呆症和夜间躁动的人的 RLS 可能是一种未确定的病因。躁动，并且使用客观措施诊断不宁腿综合症，我们发现几乎 1/4 患有不宁腿综合症，并且不宁腿综合症是与夜间躁动相关（r = 0.31，p = .01）。我们现在提议进行一项试点临床试验，以确定是否存在 RLS。治疗可以减少夜间躁动，改善睡眠，减少抗精神病药物的使用，其机制针对这些效果，我们选择加巴喷丁依那卡必 (GEn) 作为治疗方法，因为它已获得 FDA 批准。 RLS 并具有良好的安全性，我们建议进行为期 8 周的双盲安慰剂对照随机试验。在 136 名患有中度至重度阿尔茨海默病的疗养院居民中进行了 GEn 与安慰剂的试点试验，夜间躁动和 RLS，然后进行为期 8 周的抗精神病药物使用试验后评估。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 与安慰剂相比在该人群中的安全性；3) 评估效果与安慰剂相比，GEn 的大小对夜间睡眠、RLS 行为和抗精神病药物的影响 4) 探索 RLS 行为的频率是否介导 GEn 对夜间躁动行为的影响。这项研究的结果和未来的最终试验可能会改变并提高夜间治疗的护理标准躁动；减少私奔、攻击性和其他夜间躁动行为并改善睡眠。