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

阿尔茨海默病的冷漠症试验 II (ADMET II)

• 批准号: 8925760
• 负责人: Nathan Herrmann
• 金额: $ 142.66万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8925760
• 关键词: Activities of Daily Living; Address; Adverse effects; Adverse event; Affect; Affective; Agitation; Alzheimer' s Disease; Attention; Biology; Caregiver Burden; Caregivers; Cholinesterase Inhibitors; Clinical; Clinical Trials; Cognition; Cognitive; Data; Dementia; Dependence; Dependency; Direct Costs; Dopamine; Double-Blind Method; Electrocardiogram; Electrolytes; Elements; Emotional; Enhancers; Equipment and supply inventories; Evaluation; Event; FDA approved; Generic Drugs; Goals; Health; High Prevalence; Institutionalization; Interview; Language; Major Depressive Disorder; Measures; Memory; Methylphenidate; Motivation; Neuropsychological Tests; Outcome; Pathway interactions; Patients; Pharmaceutical Economics; Pharmaceutical Preparations; Placebos; Population; Productivity; Quality of life; Randomized; Randomized Controlled Trials; Reporting; Research; Research Personnel; Resources; Safety; Sampling; Site; Sleep; Societies; Symptoms; Time; Translating; adverse outcome; behavior measurement; behavioral outcome; clinical practice; clinically significant; cognitive function; cooperative study; disability; double-blind placebo controlled trial; economic cost; effective therapy; executive function; experience; follow-up; impression; improved; interest; mental state; neuropsychiatry; placebo controlled study; primary outcome; response; secondary outcome

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.]

描述（由申请人提供）：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情感反应有限。冷漠是阿尔茨海默病 (AD) 最常见的神经精神症状 (NPS) 之一，影响大约 70% 的 AD 患者，并给患者和护理人员带来严重的不良后果。冷漠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 AD 中冷漠的患病率很高且后果严重，但目前还没有针对这种情况的有效治疗方法。非药物策略似乎对 AD 冷漠的影响有限，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 AD 冷漠的生物学，以及多巴胺增强剂（如哌醋甲酯）治疗这种疾病的潜在价值。此外，我们最近报告了两项为期六周的随机对照试验的结果，显示哌甲酯在治疗 AD 冷漠方面比安慰剂具有明显的益处，以及哌甲酯的潜在认知益处和良好的安全性/耐受性。 [然而，这些研究并未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，治疗超过六周后是否有效且安全？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相结合可以转化为临床上显着的功能变化吗？ AD 冷漠的治疗对受试者的生活质量和药物经济学有影响吗？我们建议通过开展一项多中心、平行、随机、双盲、安慰剂对照研究来解决这些问题，该研究以更大的样本、更长时间的时间，评估哌醋甲酯治疗 AD 患者冷漠的效果（哌甲酯的冷漠痴呆试验-II (ADMET II)），并采用针对冷漠 AD 患者优化的一系列简洁的神经心理学测试。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研究人员，他们在第一项 ADMET 研究以及其他探索痴呆症神经精神症状治疗方法的临床试验中成功合作。]