Galantamine in AD - A 6-month randomized, placebo-controlled trial with a 6-month extension
Galantamine in AD - A 6-month randomized, placebo-controlled trial with a 6-month extension
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DOI：
10.1212/wnl.54.12.2261
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发表时间：
2000-06-27
期刊：
影响因子：
9.9
通讯作者：
Yuan, W
中科院分区：
文献类型：
--
作者：
Raskind, MA;Peskind, ER;Yuan, W
背景：加兰他敏是一种可逆的竞争性胆碱酯酶抑制剂，也能变构调节烟碱乙酰胆碱受体。这些作用机制为加兰他敏在AD中的治疗试验提供了依据。方法：对636例轻中度AD患者进行为期6个月的多中心双盲试验。患者被随机分配至安慰剂组或加兰他敏组，并逐渐增加至24或32 mg/d的维持剂量。合格患者随后进入为期6个月的24 mg/d剂量开放标签研究。主要疗效指标为11项AD评估量表认知子量表（ADAS-cog/11）和基于临床医生访谈的变化印象加护理人员输入（CIBIC-plus）。痴呆残疾评估（DAD）量表是次要疗效变量。结果如下：与安慰剂相比，加兰他敏显著改善了认知功能;第6个月时，ADAS-cog/11量表的治疗效果分别为3.9分（低剂量）和3.8分（高剂量）（两种情况下p < 0.001）。与安慰剂相比，两种剂量的加兰他敏对CIBIC-plus产生更好的结果（p < 0.05）。对加兰他敏的治疗反应不受APOE基因型的影响。在12个月时，接受加兰他敏24 mg/d治疗的患者的平均ADAS-cog/11和DAD评分与基线相比无显著变化。在长期治疗期间，最常见的不良事件（主要是胃肠道不良事件）发生频率降低。无肝毒性证据。结论：加兰他敏治疗AD安全有效。6个月时，加兰他敏显著改善了认知和整体功能。此外，24 mg/d剂量的认知和日常功能可维持12个月。
Background: Galantamine is a reversible, competitive cholinesterase inhibitor that also allosterically modulates nicotinic acetylcholine receptors. These mechanisms of action provided the rationale for a therapeutic trial of galantamine in AD. Methods: A 6-month, multicenter, double-blind trial was undertaken in 636 patients with mild to moderate AD. Patients were randomly assigned to placebo or galantamine and escalated to maintenance doses of 24 or 32 mg/d. Eligible patients then entered a 6-month, open-label study of the 24 mg/d dose. Primary efficacy measures were the 11-item AD Assessment Scale cognitive subscale (ADAS-cog/11) and the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). The Disability Assessment for Dementia (DAD) scale was a secondary efficacy variable. Results: Galantamine significantly improved cognitive function relative to placebo; the treatment effects were 3.9 points (lower dose) and 3.8 points (higher dose) on the ADAS-cog/11 scale at month 6 (p < 0.001 in both cases). Both doses of galantamine produced a better outcome on CIBIC-plus than placebo (p < 0.05). Therapeutic response to galantamine was not affected by APOE genotype. At 12 months, mean ADAS-cog/11 and DAD scores had not significantly changed from baseline for patients who received galantamine 24 mg/d throughout the 12 months. The most common adverse events, which were predominantly gastrointestinal, decreased in frequency during long-term treatment. There was no evidence of hepatotoxicity. Conclusions: Galantamine is effective and safe in AD. At 6 months, galantamine significantly improved cognition and global function. Moreover, cognitive and daily function were maintained for 12 months with the 24 mg/d dose.