Effects of STX209 (Arbaclofen) on Neurobehavioral Function in Children and Adults with Fragile X Syndrome: A Randomized, Controlled, Phase 2 Trial
Effects of STX209 (Arbaclofen) on Neurobehavioral Function in Children and Adults with Fragile X Syndrome: A Randomized, Controlled, Phase 2 Trial
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DOI：
10.1126/scitranslmed.3004214
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发表时间：
2012-09-19
影响因子：
17.1
通讯作者：
Hagerman, Randi J.
中科院分区：
文献类型：
--
作者：
Berry-Kravis, Elizabeth M.;Hessl, David;Hagerman, Randi J.
对脆性X综合征动物模型的研究表明，STX209（一种γ - 氨基丁酸B型（GABA(B)）受体激动剂）可能改善患病患者的神经行为功能。我们在一项随机、双盲、安慰剂对照交叉研究中评估了STX209是否能改善脆性X综合征的行为症状，该研究纳入了63名受试者（55名男性），年龄在6至39岁之间，其FMR1基因存在完全突变（>200个CGG三联体重复）。我们发现，在主要终点指标——异常行为检查表 - 易激惹（ABC - I）分量表上，与安慰剂相比没有差异。在方案中规定的其他分析中，在父母提名的问题行为视觉模拟量表评分上有所改善，在多个综合指标上呈现积极趋势。使用ABC - 社交回避量表（一种新验证的用于评估脆性X综合征的量表）进行的事后分析显示，在整个研究人群中治疗效果显著有益。一个由27名社交障碍更严重的受试者组成的事后亚组在温兰德II - 社会化原始评分、ABC - 社交回避量表以及所有综合指标上均有改善。STX209耐受性良好，镇静和头痛的发生率为8%，是最常见的副作用。在这项探索性研究中，STX209未显示出对脆性X综合征易激惹症状有改善作用。尽管如此，我们的研究结果表明，GABA(B)受体激动剂有改善脆性X综合征患者社交功能和行为的潜力。
Research on animal models of fragile X syndrome suggests that STX209, a gamma-aminobutyric acid type B (GABA(B)) agonist, might improve neurobehavioral function in affected patients. We evaluated whether STX209 improves behavioral symptoms of fragile X syndrome in a randomized, double-blind, placebo-controlled crossover study in 63 subjects (55 male), ages 6 to 39 years, with a full mutation in the FMR1 gene (>200 CGG triplet repeats). We found no difference from placebo on the primary endpoint, the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. In the other analyses specified in the protocol, improvement was seen on the visual analog scale ratings of parent-nominated problem behaviors, with positive trends on multiple global measures. Post hoc analysis with the ABC-Social Avoidance scale, a newly validated scale for the assessment of fragile X syndrome, showed a significant beneficial treatment effect in the full study population. A post hoc subgroup of 27 subjects with more severe social impairment showed improvements on the Vineland II-Socialization raw score, on the ABC-Social Avoidance scale, and on all global measures. STX209 was well tolerated, with 8% incidences of sedation and of headache as the most frequent side effects. In this exploratory study, STX209 did not show a benefit on irritability in fragile X syndrome. Nonetheless, our results suggest that GABA(B) agonists have potential to improve social function and behavior in patients with fragile X syndrome.