Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial.
Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial.
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DOI：
10.1016/s1474-4422(12)70320-4
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发表时间：
2013-02
期刊：
影响因子：
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通讯作者：
Miller BL
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作者：
Boxer AL;Knopman DS;Kaufer DI;Grossman M;Onyike C;Graf-Radford N;Mendez M;Kerwin D;Lerner A;Wu CK;Koestler M;Shapira J;Sullivan K;Klepac K;Lipowski K;Ullah J;Fields S;Kramer JH;Merrilees J;Neuhaus J;Mesulam MM;Miller BL
美金刚已被用于标签外治疗额颞叶变性（FTD）。先前的一项26周开放标签研究表明，通过神经精神量表（NPI）测量，对神经精神症状有短暂的适度获益。我们进行了一项随机、平行组、双盲、安慰剂对照试验，每天口服20 mg美金刚胺，持续26周。受试者符合行为变异（bvFTD）或语义性痴呆（SD）的Neary标准，并有特征性脑萎缩。禁止使用胆碱酯酶抑制剂。本研究的目的是确定美金刚是否是FTD的有效治疗方法。受试者被随机分为两组和四组，分别服用美金刚或相匹配的安慰剂。主要终点是26周后NPI总分和临床总体印象变化（CGIC）评分的变化。次要结局包括神经心理学成套测验和其他认知、总体和日常生活活动测量。Clinicaltrials.gov标识符：NCT 00545974筛选了100例受试者，81例接受随机化，5例（6%）中止治疗，76例完成所有访视。入组人数低于计划，因为许多受试者倾向于使用美金刚或胆碱酯酶抑制剂标签外，而不是参加临床试验。39名美金刚和42名安慰剂受试者进入主要意向治疗分析。治疗26周后，美金刚治疗对NPI（平均差异[MD] 2.2，95%CI：-3.9，8.3，p = 0.47）或CGIC（MD 0，95%CI：-0.4，0.4，p = 0.90）均无影响。美金刚一般耐受性良好，但是美金刚组中有更频繁的认知不良事件。在bvFTD或SD中，美金刚治疗无获益。这些数据不支持美金刚用于FTD。森林研究所
Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26 week open label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI). We performed a randomized, parallel group, double blind, placebo controlled trial of 20 mg memantine taken orally daily for 26 weeks in FTD. Participants met Neary criteria for behavioral variant (bvFTD) or semantic dementia (SD) and had characteristic brain atrophy. Use of cholinesterase inhibitors was prohibited. The objective of the study was to determine whether memantine is an effective treatment for FTD. Individuals were randomized to memantine or matched placebo tablets in blocks of two and four. Primary endpoints were the change in total NPI score and Clinical Global Impression of Change (CGIC) scores after 26 weeks. Secondary outcomes included a neuropsychological battery, and other cognitive, global and activity of daily living measures. Clinicaltrials.gov identifier: NCT00545974 100 subjects were screened, 81 were randomized, 5 (6%) discontinued and 76 completed all visits. Enrollment numbers were lower than planned due to many subjects’ preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. 39 memantine and 42 placebo subjects entered the primary intent to treat analysis. There was no effect of memantine treatment on either the NPI (mean difference [MD] 2.2, 95%CI: −3.9, 8.3, p = 0.47) or CGIC (MD 0, 95%CI: −0.4, 0.4, p = 0.90) after 26 weeks of treatment. Memantine was generally well tolerated, however there were more frequent cognitive adverse events in the memantine group. There was no benefit of memantine treatment in bvFTD or SD. These data do not support memantine use in FTD. Forest Research Institute