Spain Rebecca, Powers Katherine, Murchison Charles, Heriza Elizabeth, Winges Kimberly, Yadav Vijayshree, Cameron Michelle, Kim Ed, Horak Fay, Simon Jack, Bourdette Dennis
Neurology Division (R.S., V.Y., M.C., E.K., D.B.), Research Service (K.P., E.H.), and Department of Ophthalmology (K.W.), Veterans Affairs Portland Health Care System, OR; and Department of Neurology (R.S., C.M., K.W., V.Y., E.K., F.H., J.S., D.B.), Advanced Imaging Research Center (K.P.), and Casey Eye Institute (K.W.), Oregon Health & Science University, Portland.
Neurol Neuroimmunol Neuroinflamm. 2017 Jun 28;4(5):e374. doi: 10.1212/NXI.0000000000000374. eCollection 2017 Sep.
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, = 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, = 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.
确定内源性产生的抗氧化剂硫辛酸（LA）是否能减缓继发进展型多发性硬化症（SPMS）患者的全脑萎缩率以及是否安全。
年龄在40 - 70岁的SPMS患者参加了一项单中心、为期2年的双盲随机试验，每日口服1200毫克LA或安慰剂。主要结局是年化脑容量百分比变化（PCBV）。次要结局包括脑、脊髓和视网膜亚结构的萎缩率变化、残疾程度、生活质量及安全性。意向性分析采用线性混合模型。
研究时间为2011年5月2日至2015年8月14日。LA组（n = 27）和安慰剂组（n = 24）在平均年龄58.5（标准差5.9）岁、61%为女性、平均病程29.6（标准差9.5）年以及扩展残疾状态评分中位数6.0（四分位间距1.75）方面相匹配。2年后，LA组的年化PCBV显著低于安慰剂组（-0.21[系数估计标准误（SEE）0.14]对-0.65[SEE 0.10]，95%置信区间[CI]0.157 - 0.727，P = 0.002）。LA组改良25英尺步行时间虽几乎但未显著优于对照组（-0.535[SEE 0.358]对0.137[SEE 0.247]，95% CI -1.37至0.03，P = 0.06）。LA组胃肠道不适显著增多，跌倒显著减少。LA队列中出现了1例意外肾衰竭和1例肾小球肾炎。通过药丸计数衡量的依从性为87%。
LA使年化PCBV降低了68%，提示对SPMS有临床益处，且在2年期间保持了良好的安全性、耐受性和依从性。
NCT01188811。
本研究提供了I级证据，表明对于SPMS患者，LA可降低脑萎缩率。
