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: 7566422
• 负责人: Krista L. Lanctot
• 金额: $ 74.04万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7566422
• 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; 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; alternative treatment; base; behavior measurement; clinically significant; depression; 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）：阿尔茨海默氏症痴呆症（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了严重的不利影响。冷漠影响了大约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和Gornbein，1996; Steinberg et al。，2006; Steinberg et al。，Steinberg et al。，2007）。尽管AD中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。虽然已经对非药物治疗进行了研究，但临床经验表明可靠但有限的功效。最近的研究已经开始探索药理学选择，例如胆碱酯酶抑制剂（CHEIS）。但是Cheis似乎对冷漠而不是特定的，并且有关其功效的发现尚未得到广泛复制。抗抑郁药也被认为是一种选择，但一些证据表明它们可能有害而不是有助于对AD的冷漠治疗。因此，迫切需要更好的药理选择来治疗AD中的冷漠。多巴胺能剂表现出有望作为AD中冷漠的治疗方法。其使用的基本原理是基于多巴胺能中唇脑脑奖励系统的活动与大脑受损人群中动机行为的表达之间的牢固联系。使用多巴胺能剂的证据也来自案例报告和非征收人群中的小标签研究。来自双盲，安慰剂控制的单位点跨界试验研究的初步数据表明，多巴胺激动剂甲基苯甲酯优于安慰剂，可以治疗AD（LANCTTT，印刷中）的冷漠治疗。拟议的哌醋甲酯试验（ADMET）中提出的冷漠的目的是通过评估甲基苯甲酸酯治疗AD冷冻患者的甲基化甲酯，扩大这项令人鼓舞的初步工作。这项研究将采用多站点，平行，随机，双盲，安慰剂控制的设计。它将汇集到成功在阿尔茨海默氏病研究（DIADDS-2）和完整的临床抗精神病药疗法（CATIE-AD）的临床抗精神病药试验（CATIE-AD）中成功执行正在进行的抑郁症的研究者。 ADMET将检查哌醋甲酯在AD患者中治疗临床意义的冷漠的功效和安全性。这将是一个双盲，6周，随机，安慰剂对照试验，涉及100例AD患者。 ADMET将在门诊，疗养院和辅助生活环境中注册广告患者。该项目非常重要，因为它将探索有前途的多巴胺激动剂在AD中治疗冷漠的功效和安全性，那里没有可靠的治疗选择。如果发现哌醋甲酯有效，它可能会成为AD中冷漠的第一线治疗。此外，通过检查反应的预测因子，ADMET将为将来的研究奠定基础，以了解哌醋甲酯和其他多巴胺激动剂对冷漠的作用所涉及的机制。公共卫生相关性：患有阿尔茨海默氏病（AD）的500万美国人经历了缺乏独立性，这会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，尽管被认为是AD依赖性依赖性的少数可能治疗原因之一，但目前尚无有效的冷漠治疗方法。这项研究旨在为AD中的冷漠开发一种新的治疗方法，以减少其令人衰弱的后果，并减少患者对看护人的依赖，从而为患者及其亲人提供当之无愧的缓解。