Abstract
Weight loss, a key indicator of malnutrition in amyotrophic lateral sclerosis (ALS) patients, negatively impacts prognosis. However, effective nutritional interventions have not been adequately established. Previous research in ALS model mice has shown that L-arginine can prolong survival, yet no human intervention studies have been conducted. This study aimed to assess the safety, tolerability, and efficacy of L-arginine hydrochloride in ALS patients. ALS patients were administered 15 g/day L-arginine hydrochloride for 90 days. Safety was primarily evaluated on days 45 and 90. Efficacy measures included changes in nutritional status, ALS Functional Rating Scale 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 and body mass index (BMI) were − 0.37 kg and − 1.1 kg/m2, respectively, which are less than the typically observed natural reduction rates. There were no events requiring TPPV initiation or deaths. This study demonstrated that the oral administration of L-arginine hydrochloride across 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