NEURoaid II (MLC901) in cognitively Impaired not demenTEd patientS (NEURITES): A pilot double blind, placebo‐controlled randomized trial

OBJECTIVE: To investigate the efficacy and safety of MLC901 in vascular cognitive impairment no dementia (VCIND) patients. DESIGN: This was a multi‐center, double‐blind, randomized, placebo‐controlled pilot study. SETTING AND PARTICIPANT: VCIND patients from hospitals in Singapore (67), Vietnam (19), and the Philippines (17) were recruited and followed‐up from March 2013 to April 2018. METHODS: The primary outcome was executive function as measured by the Verbal Fluency (VF) and 2‐part Color Trails Test (CTT). The mean difference in the scores between baseline and week 12, and baseline and week 24, was compared between MLC901 and placebo using a two‐sample t‐test. RESULTS: The trial randomized 103 subjects: MLC901 (n = 57) and placebo (n = 46). The mean age of participants was 68.3 ± 8.4 years and 38.8% were female. Improvement in executive function with MLC901 was not significantly better than placebo at week 12 (CTT1 mean difference [md] 3.8 seconds, 95% confidence interval [CI]: –9.0 to 16.5, CTT2 md 10.9 seconds, 95% CI: –0.2 to 22.0), and at week 24 (CTT1 md 2.8 seconds, 95% CI: –8.4 to 14.0, CTT2 md = 4.4 seconds, 95% CI: –8.2 to 16.9). Improvement in VF from baseline was not significantly different between MLC901 and placebo at weeks 12 and 24. There were no significant differences in adverse events (43.5% vs. 56.1%) or serious adverse events (13% vs. 22.8%) in placebo versus MLC901 groups. In post hoc exploratory analysis, the treatment effect of MLC901 on cognitive function appears more apparent in subjects with existing impairment in executive function: CTT2 (md 14.4 seconds [P = .05] and 9.9 seconds [P = .3] at week 12 and week 24, respectively). CONCLUSIONS: Whilst MLC901 appears to be safe, there was no significant cognitive benefit from MLC901 in the study population. Post hoc hypotheses generating analyses suggest that VCIND patients with existing impairment in executive function may show benefit.