Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1
Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1
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DOI：
10.1212/wnl.0000000000006811
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发表时间：
2019-01-22
期刊：
影响因子：
9.9
通讯作者：
Eichler, Florian
中科院分区：
文献类型：
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作者：
Fridman, Vera;Suriyanarayanan, Saranya;Eichler, Florian
目的评价l-丝氨酸治疗遗传性感觉自主神经病变I型（HSAN1）的安全性和有效性。方法在这项开放标签扩展的随机、安慰剂对照、平行组试验中，年龄在18-70岁的有症状的HSAN1患者随机接受l-丝氨酸（400 mg/kg/天）或安慰剂治疗1年。所有参与者在第二年都服用了l-丝氨酸。主要结局指标为Charcot-Marie-Tooth神经病变评分第2版（CMTNS）。次要结局包括血浆鞘脂水平、表皮神经纤维密度、电生理测量、患者报告的测量和不良事件。在2013年8月至2014年4月期间，我们招募并随机分配了18名参与者，其中16名完成了研究。1年后，与安慰剂组相比，l-丝氨酸组的CMTNS得到改善（-1.5个单位，95% CI -2.8至-0.1,p = 0.03），有证据表明在治疗的第二年继续改善（-0.77,95% CI -1.67至0.13,p = 0.09）。同时，l-丝氨酸治疗组的脱氧鞘氨酸水平下降，而安慰剂治疗组的水平没有下降（下降59%，上升11%；p < 0.001）。没有与l-丝氨酸相关的严重不良反应。结论：大剂量口服l-丝氨酸补充剂对HSAN1患者是安全的，并可能有效减缓疾病进展。Clinicaltrials.gov识别码NCT01733407。本研究提供了一级证据，证明大剂量口服l-丝氨酸补充剂可显著减缓HSAN1患者的疾病进展。
Objective To evaluate the safety and efficacy of l-serine in humans with hereditary sensory autonomic neuropathy type I (HSAN1). Methods In this randomized, placebo-controlled, parallel-group trial with open-label extension, patients aged 18-70 years with symptomatic HSAN1 were randomized to l-serine (400 mg/kg/day) or placebo for 1 year. All participants received l-serine during the second year. The primary outcome measure was the Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS). Secondary outcomes included plasma sphingolipid levels, epidermal nerve fiber density, electrophysiologic measurements, patient-reported measures, and adverse events. Results Between August 2013 and April 2014, we enrolled and randomized 18 participants, 16 of whom completed the study. After 1 year, the l-serine group experienced improvement in CMTNS relative to the placebo group (-1.5 units, 95% CI -2.8 to -0.1, p = 0.03), with evidence of continued improvement in the second year of treatment (-0.77, 95% CI -1.67 to 0.13, p = 0.09). Concomitantly, deoxysphinganine levels dropped in l-serine-treated but not placebo-treated participants (59% decrease vs 11% increase; p < 0.001). There were no serious adverse effects related to l-serine. Conclusion High-dose oral l-serine supplementation appears safe in patients with HSAN1 and is potentially effective at slowing disease progression. Clinicaltrials.gov identifier NCT01733407. Classification of evidence This study provides Class I evidence that high-dose oral l-serine supplementation significantly slows disease progression in patients with HSAN1.