Efficacy of mecasin for treatment of amyotrophic lateral sclerosis: A phase IIa multicenter randomized double-blinded placebo-controlled trial

Abstract

Ethnopharmacological relevanceAmyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by progressive paralysis of voluntary muscles. Mecasin, the extract of modified jakyakgamchobuja-tang—a herbal preparation comprising of Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Aconiti Lateralis Preparata, Radix Salviae Miltiorrhizae, Rhizoma Gastrodiae, Radix Polygalae, Curcuma Root, Fructus Chaenomelis, and Rhizoma Atractylodis Japonicae—shows neuroprotective and anti-neuroinflammatory effects and alleviates the symptoms in patients with ALS. Aim of the studyThis trial aimed to evaluate the efficacy and safety of mecasin in these patients. Material and methodsPatients were randomized to receive mecasin 1.6 g daily, mecasin 2.4 g daily, or placebo for 12 weeks. The primary endpoint was the Korean version of ALS Functional Rating Scale-Revised (K-ALSFRS-R) score. The secondary endpoints were muscular atrophy measurements, pulmonary function test results, creatine kinase levels, body weight, safety, and scores of the Medical Research Council (MRC) scale for muscle strength; Visual Analog Scale for pain (VAS pain); Hamilton Rating Scale for Depression; and Fatigue Severity Scale. ResultsAmong the 30 patients randomized, 24 completed the follow-up. Significant between-group differences were detected in the primary endpoint using the omnibus F-test. The changes in the K-ALSFRS-R score between 12 weeks and baseline were −0·25, −1·32, and −2·78 in the mecasin 1.6 g, mecasin 2.4 g, and placebo groups, respectively. The difference in the K-ALSFRS-R score between the mecasin 1.6 g and placebo groups was 2·53 points (95% confidence interval [CI]: 0·61–4·45), and that between the 2.4 g and placebo groups was 1·46 points (95% CI: 0·48–3·40). However, no significant differences were detected in the secondary endpoints (MRC: dyspnea, p = 0·139; VAS pain, p = 0·916; forced vital capacity, p = 0·373). The incidence of adverse events was similar and low in all groups. ConclusionsMecasin may retard symptomatic progression without major adverse effects. A phase IIb study to evaluate its long-term effects in ALS is ongoing.