Metrifonate treatment of the cognitive deficits of Alzheimer's disease
Metrifonate treatment of the cognitive deficits of Alzheimer's disease
复制标题
甲曲膦酸钠治疗阿尔茨海默病认知缺陷
DOI：
10.1212/wnl.50.5.1214
复制
发表时间：
1998
期刊：
影响因子：
9.9
通讯作者：
B. Gulanski
中科院分区：
文献类型：
--
作者：
J. Cummings;P. Cyrus;F. Bieber;J. Mas;J. Orazem;B. Gulanski
对乙酰胆碱酯酶抑制剂美曲磷酯治疗轻中度阿尔茨海默病（AD）的疗效和安全性进行了临床评价。这是一项前瞻性、30周、多中心、双盲、随机、平行组、剂量探索研究，包括2周筛选期、12周治疗期以及治疗后8周和16周的随访访视。患者接受安慰剂或美曲磷酯每日一次。接受甲磺酸钠治疗的患者接受0.5 mg/kg的负荷剂量（25至45 mg），0.9 mg/kg（45至80 mg）或2.0 mg/kg（100至180 mg）给药2周，随后维持剂量为0.2 mg/kg（10至20 mg）、0.3 mg/kg（15至25 mg）或0.65 mg/kg（30至60 mg）给药10周。480例患者入组。安慰剂组完成双盲治疗的患者比例为96%，而美曲磷酯组为89%至94%。根据阿尔茨海默病评估量表-认知子量表（ADAS-Cog）的评估，美曲磷酯显著改善了认知能力，并根据临床医生基于护理人员输入的变化印象（CIBIC-Plus）的评估，增强了整体功能。在3个月时，意向治疗患者中，ADAS-Cog评分变化的治疗差异有利于美曲磷酯，为2.94分（95% CI，1.61 - 4.27;p = 0.0001）。与安慰剂组患者相比，这些患者在CIBIC-Plus组中也表现出0.35分的改善（95% CI，0.15至0.54; p = 0.0007）。接受较低药物剂量的患者在两个性能量表上的评分均介于安慰剂组和0.65 mg/kg美曲磷酯组之间。该药物耐受性良好;副作用主要是胃肠道性质的，没有观察到肝脏毒性。因此，在本研究中，美曲磷酯安全地改善了AD患者的认知缺陷，并有益于整体功能。
The efficacy and safety of metrifonate, an acetylcholinesterase inhibitor, was evaluated clinically in patients diagnosed with mild to moderate Alzheimer's disease (AD). This was a prospective, 30-week, multicenter, double-blind, randomized, parallel group, dose-finding study, which included a 2-week screening period, a 12-week treatment period, and follow-up visits at 8 and 16 weeks post-treatment. Patients received placebo or metrifonate once daily. Metrifonate-treated patients received a loading dose of 0.5 mg/kg(25 to 45 mg), 0.9 mg/kg (45 to 80 mg), or 2.0 mg/kg (100 to 180 mg) for 2 weeks, followed by a maintenance dose of 0.2 mg/kg (10 to 20 mg), 0.3 mg/kg(15 to 25 mg), or 0.65 mg/kg (30 to 60 mg) for 10 weeks. Four hundred eighty patients were enrolled. Percentages of patients completing double-blind treatment were 96% in the placebo group and 89 to 94% in the metrifonate group. Metrifonate significantly improved cognitive ability, as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and enhanced global function, as assessed the Clinicians's Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus). At 3 months, in the intent-to-treat patients, the treatment difference for the change in ADAS-Cog score in favor of metrifonate was 2.94 points (95% CI, 1.61 to 4.27;p = 0.0001). These patients also exhibited a 0.35-point improvement on the CIBIC-Plus relative to the placebo patients (95% CI, 0.15 to 0.54; p = 0.0007). Patients receiving lower drug doses had scores intermediate to those of the placebo and the 0.65 mg/kg metrifonate groups on both performance scales. The drug was well tolerated; side effects were predominantly gastrointestinal in nature, and no hepatic toxicity was observed. Therefore, in this study, metrifonate safely improved the cognitive deficits and benefited the global function of AD patients.