PDF(Pubmed)
Abstract：
ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed positive effects on self-sufficiency (defined as a score of 3+ on the ALSFRS-R items for swallowing, cutting food and handling utensils, and walking) ALSFRS-R total score and FVC. We conducted an observational, retrospective, multicentre, case-control study to provide additional data on the effects of ALCAR in subjects with ALS in Italy. Subjects treated with ALCAR 1.5 g/day or 3 g/day were included and matched with not treated subjects by sex, age at diagnosis, site of onset, and time from diagnosis to baseline, (45 subjects per group). ALCAR 3 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 23 (51.1%) treated subjects (adj. OR 1.18, 95% CI 0.46-3.02). No statistically significant differences were detected in ALSFRS nor FVC nor self-sufficiency. ALCAR 1.5 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 32 (71.1%) treated subjects (adj. OR 0.27, 95% CI 0.10-0.71). For ALSFRS-R, a mean slope of - 1.0 was observed in treated subjects compared to - 1.4 in those not treated (p = 0.0575). No statistically significant difference was detected in the FVC nor self-sufficiency. Additional evidence should be provided to confirm the efficacy of the drug and provide a rationale for the dosage.
摘要：
ALCAR（乙酰-L-肉碱）是乙酰基的供体，增加肉碱的细胞内水平，脂肪酸穿过线粒体膜的主要转运蛋白。体内研究显示ALCAR降低氧化应激标志物和促炎细胞因子。在先前的一项双盲安慰剂对照II期试验中，显示出对自给自足的积极影响（定义为吞咽的ALSFRS-R项目评分为3分，切割食物和处理器具，和步行）ALSFRS-R总分和FVC。我们进行了一次观察,回顾性,多中心,病例对照研究，以提供有关ALCAR对意大利ALS患者的影响的其他数据。纳入用ALCAR1.5g/天或3g/天治疗的受试者，并按性别与未治疗的受试者相匹配。诊断时的年龄，发病部位,从诊断到基线的时间，（每组45名受试者）。ALCAR3g/天vs未治疗：基线后24个月，22名未治疗的受试者（48.9％）仍然活着，与23名（51.1%）接受治疗的受试者相比（调整。OR1.18，95%CI0.46-3.02）。在ALSFRS，FVC和自给自足方面均未检测到统计学上的显着差异。ALCAR1.5g/天vs未治疗：基线后24个月，22名未治疗的受试者（48.9%）仍然存活，与32名（71.1%）接受治疗的受试者相比（调整。OR0.27，95%CI0.10-0.71）。对于ALSFRS-R，与未治疗的受试者相比,在治疗的受试者中观察到-1.0的平均斜率(p=0.0575)。在FVC和自给自足方面均未检测到统计学上的显着差异。应提供其他证据以确认药物的功效并提供剂量的理由。
