ALZH/SIMVA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项随机、双盲、安慰剂对照、平行组设计的III期临床试验的目的是评价辛伐他汀延缓阿尔茨海默病（AD）进展的安全性和有效性。 药物和安慰剂的随机化程度相同，采用分层、区组随机化，以确保研究中心内分配平衡。 主要结局是减缓AD的进展，通过AD评估量表（ADAScog）的认知部分进行测量。 次要结局包括临床总体变化（ADCD-CGIC）、精神状态、功能能力、行为障碍、生活质量和经济指标。 将从大约40个研究中心入组400例轻度至中度AD受试者，这些受试者没有危及生命的疾病，并且不需要降脂治疗（根据现行指南），每个研究中心的目标入组人数为10-15例。 研究药物准备如下：辛伐他汀20 mg或匹配安慰剂给药6周，随后辛伐他汀40 mg或匹配安慰剂给药18个月。 发生副作用的受试者将根据临床需要调整药物，由研究中心PI酌情决定。 疗效指标：主要指标为18个月内ADAS-cog的变化。 次要指标包括ADCS临床总体印象变化（ADCS-CGIC）、简易精神状态检查（MMSE）、依赖性量表、ADCS日常生活活动（ADCS-ADL）量表、神经精神量表（NPI）以及生活质量和药物经济学指标的18个月变化。 还将从受试者亚组的储存样本中检查淀粉样蛋白、炎症和氧化应激的生物标志物，并将收集载脂蛋白E和其他标志物用于二次分析。 安全性参数包括不良事件报告、症状检查表记录、生命体征表现、体格检查、神经系统检查和实验室检查（包括肝功能和肌酸激酶）。 作为另一个起作用的变量，DNA储存将允许检查反应的其他潜在预测因子。

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.