From the Departments of Child Neurology (P.L.P., J.S., E.S.B., J.Y.) and Biostatistics/Epidemiology (R.M., J.H.), Children's National Medical Center, Washington, DC; Clinical Epilepsy Branch (J.S., W.H.T., E.W.), NINDS, NIH, Bethesda, MD; and Clinical Pharmacology (K.M.G.), Washington State University, Spokane.
Neurology. 2014 Mar 18;82(11):940-4. doi: 10.1212/WNL.0000000000000210. Epub 2014 Feb 12.
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.
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.
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).
Adaptive behavior did not improve significantly with taurine intervention. Further therapeutic clinical trials including an on-off paradigm using biomarkers are planned.
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.
本开放性研究的主要目的是评估牛磺酸对适应行为的影响，次要目的是收集琥珀酸半醛脱氢酶缺乏症患者的安全性和耐受性数据。
在本研究中，受试者每周从起始剂量 50mg/kg/d 滴定至目标剂量 200mg/kg/d，并使用年龄标准化的适应行为评估量表评估安全性、耐受性和适应功能。
共招募了 18 名患者（8 名男性/10 名女性，年龄 0.5-28 岁，平均 12 岁）。3 名受试者因认为疗效不佳而退出。1 例严重不良事件（嗜睡住院）发生在 16g/d（200mg/kg/d），导致剂量降低方案，最大剂量为 10g/d。牛磺酸治疗后，适应领域的结果没有显示出有临床意义的改善。治疗前后的适应评分也没有统计学上的显著差异（p＞0.18）。
牛磺酸干预并没有显著改善适应行为。计划进行进一步的治疗临床试验，包括使用生物标志物的开-关范式。
本研究提供了 IV 级证据，表明对于琥珀酸半醛脱氢酶缺乏症患者，牛磺酸不会显著改善适应行为。由于缺乏对照组，该研究被评为 IV 级。
