Open AccessNEURoaid II (MLC901) in cognitively Impaired not demenTEd patientS (NEURITES): A pilot double blind, placebo‐controlled randomized trial
Author(s) -
Chen Christopher L. H.,
Nguyen Trọng Hung,
Marasigan Simeon,
Lee Chun Fan,
Lu Qingshu,
Kandiah Nagaendran,
Silva Deidre,
Chong Eddie,
Venketasubramanian Narayanaswamy
Publication year - 2021
Publication title -
alzheimer's and dementia: translational research and clinical interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.49
H-Index - 30
ISSN - 2352-8737
DOI - 10.1002/trc2.12161
Subject(s) - placebo , double blind , medicine , dementia , randomized controlled trial , psychology , audiology , physical medicine and rehabilitation , neuroscience , pathology , alternative medicine , disease
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.