Apathy in Alzheimer's Disease Methyphenidate Trial II (ADMET II)

描述(由申请者提供)：冷漠被定义为丧失意志和主动性，对活动缺乏兴趣，缺乏生产力，以及对积极或消极因素的有限情感反应。冷漠是阿尔茨海默病(AD)最常见的神经精神症状之一，约70%的AD患者会受到影响，并会给患者和照顾者带来严重的不良后果。麻木不仁的患者也更有可能需要住院治疗，这是AD直接成本的最大单一驱动因素。尽管阿尔茨海默病的冷漠及其严重后果很普遍，但这种情况还没有得到证实的治疗方法。非药物策略似乎对AD患者的冷漠作用有限，目前FDA批准的AD药物如胆碱酯酶抑制剂也是如此。最近，新的研究表明，多巴胺通路参与了阿尔茨海默病冷漠的生物学过程，以及多巴胺增强剂，如哌醋甲酯，对于治疗这种疾病的潜在价值。此外，我们最近报道了两个为期六周的随机对照试验的结果，显示在治疗AD冷漠方面，哌甲酸甲酯明显优于安慰剂，以及潜在的认知益处和良好的安全性/耐受性。[然而，这些研究没有回答一些与临床实践相关的关键问题。例如，在更大的样本中，超过六周的治疗是否有效和安全？哌醋甲酯的潜在认知益处能否在该人群中重现并保持临床意义？冷漠的减少和认知的改善结合在一起能转化为临床上显著的功能变化吗？AD患者冷漠的治疗对受试者的生活质量和药物经济学有影响吗？为了解决这些问题，我们建议进行一项多点、平行、随机、双盲、安慰剂对照的研究，在更广泛的时间段内，在更大的样本中评估哌醋甲酯治疗AD患者冷漠的疗效(痴呆患者的冷漠甲酯试验II(ADMET II))，并采用一系列针对AD冷漠患者优化的简明神经心理学测试。最终目标是收集足够有力的证据来支持临床实践的改变。这项试验将汇集一组调查人员，他们成功地合作执行了第一项ADMET研究以及探索痴呆症神经精神症状治疗的其他临床试验。]

DESCRIPTION (provided by applicant): Apathy is defined as a loss of will and initiative, lack of interest in activities, lack of productivity, as well as limited affective response to positive r negative elements . Apathy is one of the most common neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD), affecting approximately 70% of AD patients and resulting in serious adverse consequences for patients and caregivers. Apathetic patients are also more likely to require institutionalization, the largest single driver of direct costs in AD. Despite the high prevalence of apathy in AD and its serious consequences, there are no proven treatments for this condition. Nonpharmacologic strategies appear to have limited effects on apathy in AD, as do current FDA-approved medications for AD such as cholinesterase inhibitors. Recently, new research has suggested the involvement of dopamine pathways in the biology of apathy in AD and the potential value of dopamine enhancers, such as methylphenidate, for the treatment of this condition. Moreover, we have recently reported the results of two six- week randomized controlled trials showing a clear benefit of methylphenidate over placebo in treating apathy in AD, as well as potential cognitive benefits of methylphenidate and a favorable safety/tolerability profile. [However, a number of key questions relevant for clinical practice were not answered by these studies. For example, is the treatment effective and safe beyond six weeks in a larger sample? Can the potential cognitive benefit of methylphenidate be reproduced and remain clinically significant in this population? Can the combination of a decrease in apathy and an improvement in cognition be translated to clinically significant functional change? Does the treatment of apathy in AD have an impact on subject quality of life and pharmacoeconomics? We propose to address these questions by conducting a multi-site, parallel, randomized, double-blind, placebo-controlled study evaluating methylphenidate for the treatment of apathy in AD patients (Apathy in Dementia Methylphenidate Trial-II (ADMET II)) in a larger sample, over a more extensive period of time and employing a concise battery of neuropsychological tests optimized for apathetic AD patients. The ultimate goal is to collect evidence strong enough to support a change in clinical practice. This trial will bring together a team of investigators who have collaborated successfully in the execution of the first ADMET study as well as other clinical trials exploring treatments for neuropsychiatric symptoms of dementia.]