A Randomized Double-Blind, Placebo-Controlled Trial of Minocycline in Children and Adolescents with Fragile X Syndrome
A Randomized Double-Blind, Placebo-Controlled Trial of Minocycline in Children and Adolescents with Fragile X Syndrome
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DOI：
10.1097/dbp.0b013e318287cd17
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发表时间：
2013-04-01
影响因子：
2.4
通讯作者：
Hagerman, Randi J.
中科院分区：
文献类型：
--
作者：
Leigh, Mary Jacena S.;Nguyen, Danh V.;Hagerman, Randi J.
目的：米诺环素挽救脆性X小鼠模型中的突触异常并改善行为。先前的开放标签人体研究证明了脆性X综合征（FXS）患者的益处;然而，其在FXS患者中的疗效尚未在对照试验中进行评估。方法：在年龄3.5岁至16岁的FXS患者中进行的随机、双盲、安慰剂对照、交叉试验（n = 55，平均年龄9.2 [SD，3.6]岁）。参与者被随机分配接受米诺环素或安慰剂治疗3个月，然后转为另一种治疗。结果：筛选了69例受试者，随机分配了66例受试者。55例受试者（83.3%）至少完成了第一阶段，48例（72.7%）完成了整个试验。意向性治疗分析表明，与安慰剂相比，米诺环素治疗后的一个主要结局-临床总体印象量表改善显著更大（分别为2.49 +/- 0.13和2.97 +/- 0.13，p = .0173），在视觉模拟量表上焦虑和情绪相关行为的专门分析中有更大的改善（米诺环素：5.26 cm +/- 0.46 cm，安慰剂：4.05 cm +/- 0.46 cm; p = 0.0488）。二甲胺四环素和安慰剂治疗期间的副作用没有显著差异。米诺环素未发生严重不良事件。结果可能因研究设计缺陷而存在偏倚，包括受试者完成研究时揭盲、药物相关副作用揭盲以及研究者已知的初步疗效分析结果。结论：米诺环素治疗FXS患儿3个月后，总体改善优于安慰剂。治疗3个月似乎是安全的;然而，更长的试验表明，以进一步评估的好处，副作用，并与米诺环素的临床反应相关的因素。（J Dev Behav Pediatr 34：147-155，2013）
Objective: Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Previous open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Method: Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, aged 3.5 years to 16 years (n = 55, mean age 9.2 [SD, 3.6] years). Participants were randomized to minocycline or placebo for 3 months and then switched to the other treatment. Results: Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared with placebo (2.49 +/- 0.13 and 2.97 +/- 0.13, respectively, p = .0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analog Scale (minocycline: 5.26 cm +/- 0.46 cm, placebo: 4.05 cm +/- 0.46 cm; p = .0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding, and preliminary efficacy analysis results known to investigators. Conclusions: Minocycline treatment for 3 months in children with FXS resulted in greater global improvement than placebo. Treatment for 3 months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline. (J Dev Behav Pediatr 34: 147-155, 2013)