石杉碱甲治疗阿尔茨海默病的有效性和安全性的多中心双盲随机对照试验

目的：与安慰剂双盲对照评估石杉碱甲治疗轻、中度阿尔茨海默病（AD）患者的临床疗效和安全性。方法：来自全国15个中心202例可能或可能的AD患者随机接受石杉碱甲或安慰剂治疗12周。石杉碱甲组100例,400μg/,安慰剂组102例,每6周评估1次。结果：202例患者进入意向性治疗分析,其中197例患者通过末次观察前推法（LOCF）完成统计。比较石杉碱甲组和安慰剂组各种疗效评估量表的评分自基线水平至治疗6周和12周时评分变化的均值,以及治疗12周时评分和基线相比有改善的患者的比例：治疗12周和基线相比,简易精神状态检查（MMSE）平均改善2．7分;AD评估量表的认知分量表（ADAS－Cog)得分平均改善4．6分,改善至少4分者56．1％;ADAS非认知副表（ADAS－non-Cog)得分平均改善1．5分,临床好转的患者为59．2％;日常生活活动量表（ADL）得分平均改善2．4分,改善至少10％的患者32．7％;印象变化量表（CIBIC plus)获1－3分的患者为70％,1－2分者27．8％。这些指标和安慰剂组比较,两组间的差异有显著意义。总的不良反应率石杉碱甲组为3％,均为轻度、一过性反应。结论：石杉碱甲可显著改善AD患者认知功能、行为和心境障碍、日常生活活动能力和总体功能,具有良好的安全性。

Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate Alzheimer disease,a placebo-controlled,double-blind,randomized trial

OBJECTIVE: To evaluate the clinical efficacy and safety of huperzine Alpha in treatment of patients with mild to moderate Alzheimer disease (AD). METHODS: Two hundred and two patients with the diagnosis of possible or probable AD from 15 centers the nationwide were randomly divided into two groups: huperzine Alpha group (n = 100, given huperzine Alpha 400 micro g/day for 12 weeks) and placebo group (n = 102 ). Different scales were used to evaluate the cognitive function, activity of daily life (ADL), non-cognitive disorders, and overall clinical efficacy. Safety evaluation was conducted every 6 weeks. RESULTS: In comparison with the baseline data, there was an improvement of 4.6 points in cognition assessed by ADAS-Cog (P = 0.000); an improvement of 2.7 points by MMSE (P = 0.000), an improvement of 1.5 points in behavior and mood by ADAS-non-Cog (P = 0.008) with 59.2% of the patients being on the mend clinically; and an improvement of 2.4 points by ADL (P = 0.001) with the capacity of ADL improved by at least 10% among 32.75% of the patients. 70% of the patients in huperzine Alpha group scored 1 approximately 3 points, and 27.8% of them scored 1 approximately 2 points by CIBIC-plus. The proportions of patients with an improvement of >/= 4 points by ADAS-Cog were 56.1% and 12.5% in the huperzine Alpha group and placebo group respectively (P = 0.000). The proportions of patients with an improvement of >/= 4 points by MMSE were 37.8% and 10.1% in the huperzine Alpha group and placebo group respectively (P = 0.000). The proportions of patients with an improvement of 1 approximately 3 points in global rating by CIBIC-plus were 59.2% and 40.6% in the huperzine Alpha group and placebo group respectively (P = 0.01). The proportions of patients with an improvement of >/= 10% points by ADL were 32.7% and 17.2% in the huperzine Alpha group and placebo group respectively (P = 0.01). The proportions of patients with an improvement of > 0 points by ADS-non-C0g were 70.0% and 36.3% in the huperzine Alpha group and placebo group respectively (P = 0.000). Mild and transient adverse events (edema of bilateral ankles and insomnia) were observed in 3% of huperzine Alpha treated patients. CONCLUSION: A safe and effective medicine, huperzine Alpha remarkably improves the cognition, behavior, ADL,and mood of AD patients.