Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA
Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA
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DOI：
10.1212/wnl.0000000000000210
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发表时间：
2014-03-18
期刊：
影响因子：
9.9
通讯作者：
Gibson, K. Michael
中科院分区：
文献类型：
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作者：
Pearl, Phillip L.;Schreiber, John;Gibson, K. Michael
目的：这项开放标签研究的目的主要是评估牛磺酸对适应性行为的影响，其次是收集琥珀半醛脱氢酶缺乏症患者的安全性和耐受性数据。方法：在本研究中，受试者每周从起始剂量 50 mg/kg/d 滴定至目标 200 mg/kg/d，并使用年龄归一化适应性行为评估评估安全性、耐受性和适应性功能量表结果：招募了 18 名患者（8 名男性/10 名女性，年龄 0.5-28 岁，平均 12 岁）。三名受试者因认为缺乏疗效而退出。 16 g/d (200 mg/kg/d) 时发生了一项严重不良事件（因嗜睡住院），导致剂量降低范例，最大剂量为 10 g/d。结果并未显示牛磺酸治疗后适应性域有临床意义的改善。治疗前和治疗后的适应性评分也没有表现出统计学上的显着差异（p > 0.18）。结论：牛磺酸干预后适应性行为没有显着改善。计划进行进一步的治疗性临床试验，包括使用生物标志物的开关范例。证据分类：本研究提供了 IV 级证据，表明对于琥珀半醛脱氢酶缺乏的患者，牛磺酸不会显着改善适应性行为。由于没有对照组，该研究被评为 IV 级。
Objectives:The objective of this open-label study was primarily to assess the effect of taurine on adaptive behavior and secondarily to collect safety and tolerability data in patients with succinic semialdehyde dehydrogenase deficiency.Methods:In the current study, subjects were titrated weekly from a starting dose of 50 mg/kg/d to a target 200 mg/kg/d, and assessed for safety, tolerability, and adaptive functioning using age-normalized Adaptive Behavior Assessment Scales.Results:Eighteen patients (8 males/10 females, aged 0.5-28 years, mean 12 years) were recruited. Three subjects withdrew because of perceived lack of efficacy. One serious adverse event occurred (hospitalization for hypersomnia) on 16 g/d (200 mg/kg/d), leading to a dose-lowering paradigm with a maximum dose of 10 g/d. Results did not show clinically meaningful improvement in the adaptive domains after taurine therapy. Pre- and posttherapy adaptive scores also demonstrated no statistically significant difference (p > 0.18).Conclusions:Adaptive behavior did not improve significantly with taurine intervention. Further therapeutic clinical trials including an on-off paradigm using biomarkers are planned.Classification of evidence:This study provides Class IV evidence that for patients with succinic semialdehyde dehydrogenase deficiency, taurine does not significantly improve adaptive behavior. The study is rated Class IV because of the absence of a control group.