AD

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。 这是一项随机、安慰剂对照、双盲、多中心、为期两年的丙戊酸盐治疗试验，目标剂量为10-12 mg/kg/d，对象为300名轻中度AD患者，他们在基线和发病后缺乏躁动和精神障碍。参与者将定期前往诊所就诊，并进行电话联系，以评估行为、认知、功能、安全性和耐受性。之所以选择丙戊酸盐，是因为它可能对阿尔茨海默病激越的症状有效，在许多临床人群中已知的安全性，以及最近的数据支持其在阿尔茨海默病中的神经保护潜力。主要的假设是，对基线缺乏躁动和精神病的AD患者长期服用丙戊酸盐将延缓躁动和/或精神病的出现。这种性质的影响可能会对公共卫生产生重大影响，例如，通过推迟灌输。 次要假设也将被提及。其中第一个问题是，对AD患者长期服用丙戊酸盐将减缓疾病的临床进展，以认知或功能下降的速度来衡量。参与者将留在研究中，并根据协议被跟踪两年，即使他们过早停止实验性治疗，以检查对认知或功能下降进展的可能影响。此外，慢性低剂量治疗的安全性和耐受性也将得到解决。将获得生物标本，以研究选定的与疾病相关的标记，以及假定的治疗作用机制。核磁共振扫描将在试验性治疗之前和一年后在一组参与者中进行，以解决脑容量测量中可能存在的药物-安慰剂差异。在双盲阶段之后，将有一个为期2个月的单盲安慰剂控制的洗脱阶段，以解决停药是否会对第24至26个月的行为、认知、功能或疾病严重程度的全球衡量造成不同的影响。

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. This is a randomized, placebo-controlled, double blind, multicenter, two-year trial of valproate therapy at a target dose of 10-12 mg/kg/d in 300 outpatients with mild to moderate AD who lack agitation and psychosis at baseline and since onset of illness. Participants will have regular clinic visits as well as telephone contacts for assessment of behaviour, cognition, function, safety and tolerability. Valproate was selected because of its possible symptomatic efficacy for agitation in AD, known safety profile in numerous clinical populations, and in view of recent data supporting its neuroprotective potential in AD. The primary hypothesis is that chronic valproate administration to participants with AD who lack agitation and psychosis at baseline will delay the emergence of agitation and/or psychosis. An effect of this nature may have significant public health implications, for instance, by delaying instutionalization. Secondary hypotheses will addressed as well. The first of these is that chronic valproate administration to participants with AD will attenuate clinical progression of illness measured by reduced rate of cognitive or functional decline. Participants will remain in the study and be followed per protocol for two years even if they discontinue experimental treatment prematurely, in order to examine possible effects on progression of cognitive or functional decline. In addition, the safety and tolerability of chronic low dose therapy will be addresed. Biological specimens will be obtained to study markers selected for their relevance to the diseases as well as the postulated mechanism of action of the therapy. MRI scans will be performed prior to experimentaltreatment and after one year in a subset of participants in order to address possible drug-placebo differences in brain volume measures. After the double-blind phase, there will be a 2-month single-blind placebo-controlled washout phase to address whether withdrawal will result in differential effects on behavior, cognition, function, or global measures of diseases severity from month 24 to 26.