Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: A controlled trial
Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: A controlled trial
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DOI：
10.1089/cap.2006.16.525
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发表时间：
2006-10-01
影响因子：
1.9
通讯作者：
Hagerman, Randi
中科院分区：
文献类型：
--
作者：
Berry-Kravis, Elizabeth;Krause, Sue Ellen;Hagerman, Randi
进行了一项为期 4 周的 II 期随机、双盲、安慰剂对照临床试验，以评估 Ampakine 化合物 CX516 作为脆性 X 综合征 (FXS) 潜在疾病的潜在治疗方法的安全性和有效性。基线筛选后，FXS 受试者 (n = 49) 接受为期 1 周的安慰剂导入，然后随机接受研究药物或安慰剂，为期 4 周。在治疗前、治疗结束时和治疗后两周进行认知和行为结果测量。副作用很小，安全参数没有显着变化，也没有严重的不良事件。 CX516 组中过敏性皮疹的发生率为 12.5%，其中 1 名受试者出现严重皮疹。与安慰剂相比，CX516 治疗受试者的记忆力（主要结果指标）或语言、注意力/执行功能、行为和整体功能的次要指标也没有显着改善。这项研究确实表明，在 FXS 人群的重测环境中，许多结果测量是可重复的，但有些测量过于困难或可变。患有 FXS 的成年受试者能够完成密集的临床试验，并为未来的 FXS 试验设计确定了一些有效的结果指标。其他研究中 CX516 的效力问题表明剂量可能不足以达到治疗效果，因此尚不清楚 AMPA 介导的神经传递调节是否是治疗 FXS 的可行治疗策略。
A Phase II, 4-week randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety and efficacy of the Ampakine compound CX516 as a potential treatment for the underlying disorder in fragile X syndrome (FXS). After baseline screening, subjects with FXS (n = 49) underwent a 1-week placebo lead-in and then were randomized to study drug or placebo for a 4-week period. Cognitive and behavioral outcome measures were administered prior to treatment, at the end of treatment, and 2 weeks posttreatment. There were minimal side effects, no significant changes in safety parameters, and no serious adverse events. There was a 12.5% frequency of allergic rash in the CX516 group and 1 subject developed a substantial rash. There was also no significant improvement in memory, the primary outcome measure, or in secondary measures of language, attention/executive function, behavior, and overall functioning in CX516-treated subjects compared to placebo. This study did demonstrate that many outcome measures were reproducible in this test-retest setting for the FXS population, yet some were too difficult or variable. Adult subjects with FXS were able to complete an intensive clinical trial, and some valid outcome measures were identified for future FXS trial design. Problems with potency of CX516 in other studies have suggested dosing may have been inadequate for therapeutic effect and thus it remains unclear whether modulation of AMPA-mediated neurotransmission is a viable therapeutic strategy for the treatment of FXS.