Lipoic acid in secondary progressive MS: A randomized controlled pilot trial.
Lipoic acid in secondary progressive MS: A randomized controlled pilot trial.
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DOI：
10.1212/nxi.0000000000000374
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发表时间：
2017-09
期刊：
影响因子：
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通讯作者：
Bourdette D
中科院分区：
文献类型：
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作者：
Spain R;Powers K;Murchison C;Heriza E;Winges K;Yadav V;Cameron M;Kim E;Horak F;Simon J;Bourdette D
为了确定是否硫辛酸（LA），内源性产生的抗氧化剂，减缓全脑萎缩率，并在继发性进展型MS（SPMS）是安全的。40-70岁的SPMS患者入组了一项为期2年的单中心、双盲、随机化试验，每日口服1，200 mg LA与安慰剂相比。主要结果是年化百分比变化脑体积（PCBV）的变化。次要结果是节段性脑、脊髓和视网膜亚结构萎缩率、残疾、生活质量和安全性的变化。意向治疗分析使用线性混合模型。参与时间为2011年5月2日至2015年8月14日。LA组（n = 27）和安慰剂组（n = 24）的平均年龄为58.5（SD 5.9）岁，61%为女性，平均病程为29.6（SD 9.5）年，中位扩展残疾状态评分为6.0（四分位数间距1.75）。2年后，LA组的年PCBV显著低于安慰剂组（−0.21 [估计系数的标准误（SEE）0.14] vs −0.65 [SEE 0.10]，95%置信区间[CI] 0.157-0.727，p = 0.002）。LA组的改良计时25英尺步行几乎优于对照组，但无显著性差异（−0.535 [SEE 0.358] vs 0.137 [SEE 0.247]，95% CI −1.37至0.03，p = 0.06）。LA患者的胃肠道不适明显更多，福尔斯更少。LA队列中发生了非预期肾衰竭（n = 1）和肾小球肾炎（n = 1）。按药丸数量衡量，依从性为87%。LA显示年PCBV降低68%，表明SPMS的临床获益，同时在2年内保持良好的安全性、耐受性和依从性。NCT 01188811。这项研究提供了I类证据，证明对于SPMS患者，LA可降低脑萎缩率。
To determine whether lipoic acid (LA), an endogenously produced antioxidant, slowed the whole-brain atrophy rate and was safe in secondary progressive MS (SPMS). Patients with SPMS aged 40–70 years enrolled in a single center, 2-year, double-blind, randomized trial of daily oral 1,200 mg LA vs placebo. Primary outcome was change in annualized percent change brain volume (PCBV). Secondary outcomes were changes in rates of atrophy of segmented brain, spinal cord, and retinal substructures, disability, quality of life, and safety. Intention-to-treat analysis used linear mixed models. Participation occurred between May 2, 2011, and August 14, 2015. Study arms of LA (n = 27) and placebo (n = 24) were matched with mean age of 58.5 (SD 5.9) years, 61% women, mean disease duration of 29.6 (SD 9.5) years, and median Expanded Disability Status Score of 6.0 (interquartile range 1.75). After 2 years, the annualized PCBV was significantly less in the LA arm compared with placebo (−0.21 [standard error of the coefficient estimate (SEE) 0.14] vs −0.65 [SEE 0.10], 95% confidence interval [CI] 0.157–0.727, p = 0.002). Improved Timed 25-Foot Walk was almost but not significantly better in the LA than in the control group (−0.535 [SEE 0.358] vs 0.137 [SEE 0.247], 95% CI −1.37 to 0.03, p = 0.06). Significantly more gastrointestinal upset and fewer falls occurred in LA patients. Unexpected renal failure (n = 1) and glomerulonephritis (n = 1) occurred in the LA cohort. Compliance, measured by pill counts, was 87%. LA demonstrated a 68% reduction in annualized PCBV and suggested a clinical benefit in SPMS while maintaining favorable safety, tolerability, and compliance over 2 years. NCT01188811. This study provides Class I evidence that for patients with SPMS, LA reduces the rate of brain atrophy.