ALZH/SIMVA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项随机、双盲、安慰剂对照、平行分组设计的第三阶段临床试验的目的是评估辛伐他汀延缓阿尔茨海默病(AD)进展的安全性和有效性。将对药物和安慰剂进行平等的随机化，采用分层、分块的随机化，以确保站点内的均衡分配。根据AD评估量表(ADAScog)的认知部分衡量，主要结果是减缓AD的进展。次要结果包括临床全球变化测量(ADCD-CGIC)、精神状态、功能能力、行为障碍、生活质量和经济指标。400名轻中度AD患者，没有危及生命的疾病，不需要降脂治疗(根据目前的指导方针)，将从大约40个地点招募，每个地点的目标是10-15名受试者。研究药物的准备如下：给予辛伐他汀20毫克或匹配的安慰剂，为期6周，随后给予辛伐他汀40毫克或匹配的安慰剂，持续18个月。出现副作用的受试者将根据临床需要调整药物，由现场PI自行决定。疗效测量：主要测量将是ADAS-COG在18个月内的变化。二次测量包括18个月ADCS临床总体变化印象(ADCS-CGIC)、简易精神状态检查(MMSE)、依赖量表、ADCS-ADL量表、神经精神病量表(NPI)、生活质量和药物经济学测量。还将从部分受试者的存储样本中检查淀粉样蛋白、炎症和氧化应激的生物标记物，并收集载脂蛋白E和其他标记物进行二次分析。安全参数包括不良事件的报告、症状清单的记录以及生命体征、体检、神经检查和实验室测试(包括肝功能和肌酸激酶)的表现。作为另一个起作用的变量，DNA存储将允许检查其他潜在的反应预测因素。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this randomized, double-blind, placebo-controlled, parallel group designed Phase III clinical trial is to evaluate the safety and efficacy of simvastatin to slow the progression of Alzehimer's Disease (AD). There will be equal randomization to drug and placebo, with stratified, blocked randomization to insure balanced assignment within sites. The primary outcome is slowing the progression of AD, as measured by the cognitive portion of the AD Assessment Scale (ADAScog). Secondary outcomes include measures of clinical global change (ADCD-CGIC), mental status, functional ability, behavioral disturbances, quality of life and economic indicators. Four hundred subjects with mild to moderate AD who are free of life-threatening disease and who do not require lipid-lowering treatment (according to current guidelines) will be enrolled from approximately 40 sites, with a goal of 10-15 subjects enrolled at each site. Study medications will be prepared as follows: Simvastatin 20mg or matching placebo will be given for a period of 6 weeks, followed by simvastatin 40mg or matching placebo for the remainder of 18 months. Subjects who experience side effects will have medications adjusted as clinically warranted, at the discretion of the site PI. Efficacy Measures: The primary measure will be a change on the ADAS-cog over 18 months. Secondary measures include eighteen month changes on the ADCS Clinical Global Impression of Change (ADCS-CGIC), the Mini-Mental State Examination (MMSE), the Dependence Scale, the ADCS Activities of Daily Living (ADCS-ADL) scale, the Neuropsychiatric Inventory (NPI), and the Quality of Life and Pharmacoeconomic Measure. Biomarkers of amyloid, inflammation and oxidative stress will also be examined from stored samples in a subset of subjects, and apolipoprotein E and other markers will be collected for secondary analysis. Safety parameters include the reporting of adverse events, the recording of symptom checklists, and the performance of vital signs, physicals, neurological examinations and laboratory tests (including liver function and creatine kinase). As another contributing variable, DNA storage will permit examination of other potential predictors of response.