Seritan Andreea L, Nguyen Danh V, Mu Yi, Tassone Flora, Bourgeois James A, Schneider Andrea, Cogswell Jennifer B, Cook Kylee R, Leehey Maureen A, Grigsby Jim, Olichney John M, Adams Patrick E, Legg Wendi, Zhang Lin, Hagerman Paul J, Hagerman Randi J
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J Clin Psychiatry. 2014 Mar;75(3):264-71. doi: 10.4088/JCP.13m08546.
Memantine, an uncompetitive N-methyl-d-aspartate receptor antagonist, is currently approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer's disease. Anecdotal reports have suggested that memantine may improve neurologic and cognitive symptoms of individuals with the neurodegenerative disease fragile X-associated tremor/ataxia syndrome (FXTAS); however, its efficacy and safety in this population have not been assessed in a controlled trial.
Individuals with FXTAS aged 34-80 years were enrolled in a randomized, double-blind, placebo-controlled, 1-year trial between September 2007 and August 2012. Inclusion required definite, probable, or possible FXTAS in clinical stages 1-5 according to previously published criteria. Primary outcome measures were the Behavioral Dyscontrol Scale (BDS) score and CATSYS intention tremor severity.
Ninety-four participants were randomized from 205 screened; of those, 43 and 45 started treatment with memantine (titrated to 10 mg twice daily) and placebo, respectively. Thirty-four participants receiving memantine and 36 receiving placebo completed the 1-year endpoint assessment (n = 70). Intention-to-treat analysis showed no improvement with respect to intention tremor severity (mean [SD] values with memantine vs placebo: 1.05 [0.73] vs 1.89 [2.19], P = .047) or BDS score (16.12 [5.43] vs 15.72 [3.93], P = .727) at follow-up. Post hoc analyses of participants with early FXTAS (stage ≤ 3), those with late FXTAS (stage > 3), and those in different age groups (≤ 65 years and > 65 years) also indicated no significant improvement. More frequent mild adverse events were observed in the placebo group, while more frequent moderate adverse events occurred in the memantine group (P = .007).
This randomized, double-blind, placebo-controlled trial of memantine for individuals with FXTAS showed no benefit compared to placebo with respect to the selected outcome measures.
ClinicalTrials.gov identifier: NCT00584948.
美金刚是一种非竞争性N-甲基-D-天冬氨酸受体拮抗剂，目前已获美国食品药品监督管理局批准用于治疗中重度阿尔茨海默病。有传闻称，美金刚可能改善患有神经退行性疾病脆性X相关震颤/共济失调综合征（FXTAS）患者的神经和认知症状；然而，其在该人群中的疗效和安全性尚未在对照试验中得到评估。
2007年9月至2012年8月期间，年龄在34至80岁的FXTAS患者参加了一项为期1年的随机、双盲、安慰剂对照试验。根据先前公布的标准，纳入标准为临床1至5期明确、可能或疑似FXTAS。主要结局指标为行为失控量表（BDS）评分和CATSYS意向性震颤严重程度。
205名筛查对象中有94名被随机分组；其中，43名和45名分别开始接受美金刚（滴定至每日两次，每次10毫克）和安慰剂治疗。34名接受美金刚治疗的参与者和36名接受安慰剂治疗的参与者完成了1年的终点评估（n = 70）。意向性分析显示，随访时意向性震颤严重程度（美金刚与安慰剂的均值[标准差]值：1.05[0.73]对1.89[2.19]，P = 0.047）或BDS评分（16.12[5.43]对15.72[3.93]，P = 0.727）均无改善。对早期FXTAS（≤3期）、晚期FXTAS（>3期）以及不同年龄组（≤65岁和>65岁）参与者的事后分析也表明无显著改善。安慰剂组观察到更频繁的轻度不良事件，而美金刚组观察到更频繁的中度不良事件（P = 0.007）。
这项针对FXTAS患者的美金刚随机、双盲、安慰剂对照试验显示，就选定的结局指标而言，与安慰剂相比并无益处。
ClinicalTrials.gov标识符：NCT00584948。
