Apathy in Alzheimer's Disease Methylphenidate Trial

阿尔茨海默病哌甲酯试验中的冷漠

• 批准号: 7934637
• 负责人: Krista L. Lanctot
• 金额: $ 70.96万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934637
• 关键词: Activities of Daily Living; Adverse effects; Adverse event; Affect; Affective; Alzheimer' s Disease; American; Antidepressive Agents; Antipsychotic Agents; Assisted Living Facilities; Bathing; Behavioral Symptoms; Brain; Brain Injuries; Caregivers; Caring; Case Study; Cholinesterase Inhibitors; Clinical; Cognition; Cognitive; Communities; Data; Dementia; Dependency; Direct Costs; Disease; Disease Progression; Dopamine Agonists; Dopaminergic Agents; Double-Blind Method; Effectiveness of Interventions; Electrocardiogram; Electrolytes; Elements; Emotional; Enrollment; Equipment and supply inventories; Ethics; Evaluation; Follow-Up Studies; Foundations; Future; Goals; High Prevalence; Institutionalization; Intervention Trial; Interview; Leadership; Measures; Mental Depression; Methylphenidate; Motivation; Neurobehavioral Manifestations; Neuropsychological Tests; Nursing Homes; Outcome; Outpatients; Participant; Patients; Pharmaceutical Preparations; Physicians; Pilot Projects; Placebo Control; Placebos; Population; Productivity; Public Health; Randomized; Recruitment Activity; Reporting; Research; Research Personnel; Rewards; Safety; Severities; Site; Sterile coverings; Symptoms; System; Telephone Interviews; Testing; Time; Trail Making Test; Work; adverse outcome; alternative treatment; base; behavior measurement; clinically significant; design; double-blind placebo controlled trial; economic cost; effective therapy; experience; functional disability; impression; improved; interest; loved ones; meetings; mental state; motivated behavior; neuropsychiatry; neuropsychological; open label; patient population; performance tests; placebo controlled study; primary outcome; public health relevance; randomized placebo controlled trial; residence; response; secondary outcome; therapy development; treatment strategy

DESCRIPTION (provided by applicant): Apathy in Alzheimer's dementia (AD) is a significant public health problem with serious adverse consequences for patients and caregivers. Apathy affects approximately 70% of AD patients, making it one of the most common neuropsychiatric symptoms (M. S. Mega, Cummings, Fiorello, & Gornbein, 1996; Steinberg et al., 2006; Steinberg et al., 2007). Despite the high prevalence of apathy in AD, there are no proven treatments for this condition. While non-pharmacologic treatments have been understudied, clinical experience suggests reliable but limited efficacy. Recent studies have begun to explore pharmacologic options, such as cholinesterase inhibitors (ChEIs). But ChEIs appear to be non-specific to apathy and findings regarding their efficacy have not been widely replicated. Antidepressant medications have also been considered as an option, but some evidence suggests that they could be detrimental rather than helpful in the treatment of apathy in AD. Therefore, better pharmacologic options are urgently needed for the treatment of apathy in AD. Dopaminergic agents show promise as treatments for apathy in AD. The rationale for their use is based on the strong tie between activity of the dopaminergic mesolimbic brain reward system and the expression of motivated behaviors in brain damaged populations. Evidence for the use of dopaminergic agents also comes from case reports and small open-label studies in nondemented populations. Preliminary data from a double blind, placebo controlled single-site crossover pilot study suggest that the dopamine agonist methylphenidate was superior to placebo for the treatment of apathy in AD (Lancttt, in press). The goal of the proposed Apathy in Dementia Methylphenidate Trial (ADMET) is to expand upon this encouraging preliminary work by evaluating methylphenidate for the treatment of AD patients with apathy. This study will employ a multi-site, parallel, randomized, double-blind, placebo-controlled design. It will bring together investigators who have collaborated successfully in the execution of the ongoing Depression in Alzheimer's Disease study (DIADS-2) and the completed Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE-AD). ADMET will examine the efficacy and safety of methylphenidate for the treatment of clinically significant apathy in AD patients. It will be a double-blind, 6 week, randomized, placebo-controlled trial involving 100 patients with AD. ADMET will enroll AD patients from outpatient, nursing home, and assisted living settings. This project is of great importance because it will explore the efficacy and safety of a promising dopamine agonist for treating apathy in AD, where there are no proven treatment options. Should methylphenidate be found effective, it will likely become a first line therapy for apathy in AD. In addition, by examining predictors of response, ADMET will lay the foundation for future studies to understand the mechanisms involved in the effects of methylphenidate and other dopamine agonists on apathy. PUBLIC HEALTH RELEVANCE: The 5 million Americans who suffer from Alzheimer's disease (AD) experience a lack of independence that contributes to the large emotional and economic costs of this disease. Apathy is one of the most common behavioral symptoms of AD and although it is thought to be one of the few potentially treatable causes of dependency in AD, currently there are no effective treatments for apathy. This study aims to develop a new treatment for apathy in AD that could decrease its debilitating consequences and reduce patients' dependency on caregivers, providing well-deserved relief to patients and their loved ones.

描述（由申请人提供）：阿尔茨海默氏痴呆症（AD）中的冷漠是一个重大的公共卫生问题，对患者和护理人员造成严重的不良后果。冷漠影响大约70%的AD患者，使其成为最常见的神经精神症状之一（M。S. Mega，Cummings，Fiorello，& Gornbein，1996; Steinberg et al.，2006; Steinberg等人，2007年）。尽管在AD中冷漠的患病率很高，但对于这种情况没有经过证实的治疗方法。虽然非药物治疗尚未充分研究，但临床经验表明疗效可靠但有限。最近的研究已经开始探索药理学的选择，如胆碱酯酶抑制剂（ChEI）。但ChEI似乎对冷漠没有特异性，关于其疗效的发现尚未得到广泛复制。抗抑郁药物也被认为是一种选择，但一些证据表明，它们可能是有害的，而不是有助于治疗AD的冷漠。因此，迫切需要更好的药物选择来治疗AD中的情感淡漠。多巴胺能药物显示出治疗AD冷漠的前景。其使用的基本原理是基于多巴胺能中脑边缘奖励系统的活动与脑损伤人群中动机行为的表达之间的紧密联系。多巴胺能药物使用的证据也来自非痴呆人群的病例报告和小型开放标签研究。一项双盲、安慰剂对照的单中心交叉初步研究的初步数据表明，多巴胺激动剂哌甲酯治疗AD患者的情感淡漠上级安慰剂（Lancttt，出版中）。拟开展的冷漠型哌甲酯痴呆症试验（ADMET）的目的是通过评估哌甲酯治疗冷漠型AD患者的效果，扩大这一令人鼓舞的初步工作。本研究将采用多中心、平行、随机、双盲、安慰剂对照设计。它将汇集成功合作执行正在进行的阿尔茨海默病抑郁症研究（DIADS-2）和已完成的干预有效性临床抗精神病药物试验（CATIE-AD）的研究人员。ADMET将检查哌甲酯治疗AD患者临床显著冷漠的疗效和安全性。这将是一项双盲、6周、随机、安慰剂对照试验，涉及100例AD患者。ADMET将从门诊、疗养院和辅助生活环境中招募AD患者。该项目非常重要，因为它将探索一种有前途的多巴胺激动剂治疗AD冷漠症的有效性和安全性，在这种情况下没有经过验证的治疗方案。如果哌醋甲酯被发现有效，它将可能成为AD冷漠症的一线治疗。此外，通过检查反应的预测因子，ADMET将为未来的研究奠定基础，以了解哌醋甲酯和其他多巴胺激动剂对冷漠的影响所涉及的机制。公共卫生相关性：患有阿尔茨海默病（AD）的500万美国人缺乏独立性，导致这种疾病的巨大情感和经济成本。冷漠是AD最常见的行为症状之一，尽管它被认为是AD依赖性的少数几个潜在可治疗的原因之一，但目前还没有有效的治疗方法。这项研究旨在开发一种新的治疗AD冷漠的方法，可以减少其衰弱的后果，减少患者对照顾者的依赖，为患者及其亲人提供当之无愧的救济。