Naito Hiroyuki, Nakamori Masahiro, Toko Megumi, Hayashi Yuki, Tazuma Taku, Watanabe Tomoaki, Ishihara Keito, Tachiyama Keisuke, Yamazaki Yu, Maruyama Hirofumi
Department of Clinical Neuroscience and Therapeutics, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, 734-8551, Japan.
Sci Rep. 2025 Jan 7;15(1):1120. doi: 10.1038/s41598-024-84944-6.
Weight loss, a key indicator of malnutrition in amyotrophic lateral sclerosis (ALS) patients, negatively impacts patient prognosis. However, effective nutritional interventions have not been adequately established. Research in ALS model mice has shown that L-arginine can prolong survival; however, no human intervention studies have been conducted. We conducted a single-center, single-arm, prospective, open-label, and comparative trial to assess the safety and tolerability of L-arginine hydrochloride in ALS patients. ALS patients were administered 15 g/day L-arginine hydrochloride for 90 days. The primary outcome of safety was evaluated on days 45 and 90. The secondary outcome of efficacy was evaluated by measuring nutritional status, ALS Functional Rating Scale (ALSFRS) scores, and the occurrence of events such as the initiation of tracheostomy positive pressure ventilation (TPPV) and death. The study included 20 patients (40% female; mean age, 62.0 ± 6.9 years; median disease duration, 1.9 years). Six participants (30%) experienced treatment-emergent adverse events (TEAEs), including elevated creatine kinase levels, liver function test abnormalities, glucose tolerance issues, hyperammonemia, anorexia, dysgeusia, and vasculitis. No serious TEAEs were associated with L-arginine hydrochloride. Over the course of three months, the average changes in body weight, body mass index, and the ALSFRS score were - 0.37 kg, -1.1 kg/m, and - 1.7 points, respectively. There were no events requiring TPPV initiation or deaths. This study demonstrated that the oral administration of L-arginine hydrochloride over three months was well tolerated by ALS patients, with no serious TEAEs or deaths attributed to the study drug.Trial Registration number: Japan Registry of Clinical Trials (jRCTs061230001), first registered 11/04/2023.
体重减轻是肌萎缩侧索硬化症（ALS）患者营养不良的关键指标，对患者预后产生负面影响。然而，有效的营养干预措施尚未得到充分确立。对ALS模型小鼠的研究表明，L-精氨酸可以延长生存期；然而，尚未进行人体干预研究。我们开展了一项单中心、单臂、前瞻性、开放标签的对照试验，以评估盐酸L-精氨酸在ALS患者中的安全性和耐受性。给予ALS患者每日15克盐酸L-精氨酸，持续90天。在第45天和第90天评估安全性的主要结局。通过测量营养状况、ALS功能评定量表（ALSFRS）评分以及气管切开正压通气（TPPV）启动和死亡等事件的发生情况来评估疗效的次要结局。该研究纳入了20名患者（40%为女性；平均年龄62.0±6.9岁；疾病持续时间中位数为1.9年）。6名参与者（30%）出现了治疗中出现的不良事件（TEAE），包括肌酸激酶水平升高、肝功能检查异常、葡萄糖耐量问题、高氨血症、厌食、味觉障碍和血管炎。没有严重的TEAE与盐酸L-精氨酸相关。在三个月的时间里，体重、体重指数和ALSFRS评分的平均变化分别为-0.37千克、-1.1千克/米和-1.7分。没有需要启动TPPV或死亡的事件。本研究表明，ALS患者口服盐酸L-精氨酸三个月耐受性良好，没有严重的TEAE或归因于研究药物的死亡。试验注册号：日本临床试验注册中心（jRCTs061230001），首次注册于2023年4月11日。
