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: 9318680
• 负责人: Nathan Herrmann
• 金额: $ 10万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9318680
• 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; 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; neuropsychiatric symptom; 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）：冷漠被定义为失去意志和主动性，对活动缺乏兴趣，缺乏生产力以及对正r负面因素的情感反应有限。冷漠是阿尔茨海默氏病（AD）最常见的神经精神症状（NPS）之一，影响了大约70％的AD患者，并对患者和看护者造成了严重的不良后果。冷漠患者也更有可能需要制度化，这是广告中直接成本的最大单一驱动因素。尽管AD及其严重后果的冷漠症患病率很高，但对于这种情况仍未得到证实的治疗方法。非药物策略似乎对AD中的冷漠影响有限，当前对AD（例如胆碱酯酶抑制剂）的AD药物也有限。最近，新的研究表明，多巴胺途径参与了AD的冷漠生物学以及多巴胺增强剂（例如甲基苯甲酸酯）的潜在值，以治疗这种情况。此外，我们最近报道了两项为期6周的随机对照试验的结果，表明哌醋甲酯比安慰剂在治疗AD中的冷漠以及甲基甲酯的潜在认知益处以及有利的安全性/耐受性概况。 [但是，这些研究没有回答与临床实践有关的许多关键问题。例如，在更大的样本中，治疗是否有效且安全超过六个星期？可以再现哌醋甲酯的潜在认知益处并在该人群中保持临床意义吗？冷漠减少和认知改善的结合是否可以转化为临床上显着的功能变化？ AD中冷漠的治疗是否会影响学科的生活质量和药物经济学？ 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.最终目标是收集足够强大的证据以支持临床实践的变化。这项试验将汇集一组研究人员，他们成功地在执行第一个ADMET研究中以及其他临床试验中探索了痴呆症神经精神症状的治疗方法。