Journal Article

A double-blind, placebo-controlled, randomized, multi-centre, phase III study of MLC901 (NeuroAiDTMII) for the treatment of cognitive impairment after mild traumatic brain injury

Grigoryeva, Vera N., Mkrtchan, Nona N., Jones, Kelly, Gavrik, Maxim M., Khrulev, Alexey Y., Rabarova, Daria, Barker-Collo, Suzanne, Kotsiubinskaya, Yulia V., Feigin, Valery L., Majdan, Marek, Ivanova, Anna A., Valkovic, Peter, Pilipenko, Pavel I., Skorokhodov, Anatoly V.

2025

Overview

About half of the world population will suffer from a traumatic brain injury (TBI) during their lifetime, of which about 90% of cases are mild TBI. Although up to 40% of adults with mild TBI experience persistent functional deficits, there is no proven-effective treatment to facilitate recovery after it. This randomized placebo-controlled multi-centre study was aimed to examine the efficacy of herbal supplement MLC901 on complex attention following mild TBI at 6 months post-randomisation, as a primary outcome measured by CNS Vital signs (CNS-VS). Adults aged 18-65 years, who were 1-12-months post-mild TBI and experienced cognitive impairment, were randomly assigned to receive either MLC901 two capsules (0.4g/capsule) or placebo three times a day for 6 months using centralized stratified permuted block randomization. Secondary outcomes: Rivermead Post-Concussion Symptoms Questionnaire (RPQ; neurobehavioral sequelae); Health Related Quality of Life (QOLIBRI); Hospital Anxiety and Depression Scale (HADS); and safety. Mixed effects models of repeated measures with intention to treat analysis were employed. A Least Square Mean Difference (LSMD) from baseline to 3-, 6-, and 9-month follow-up was calculated with 95% confidence intervals (CI). In the analysis, 182 participants (47.8% females) were included. Multivariable mixed effects model analysis did not reveal significant improvements in complex attention (LSMD = -1.18 [95% CI -5.40; 3.03; p = 0.58]) and other cognitive domains at 6 months in the MLC901 group compared to the Placebo group. There were significant improvements in RPQ, QOLIBRI, anxiety and depression in the MLC901 group compared to the Placebo group at 6 and 9 months (LSMD -4.36 [-6.46; -2.26] and -4.07 [-6.22; -1.92], 4.84 [1.58; 8.10] and 3.74 [0.44; 7.03], -1.50 [-2.29; -0.71 and -0.96 [-1.84; -0.08], -1.14 [-1.92; -0.35] and -1.14 [-1.94; -0.34]), respectively. MLC901 tested was proven safe. Although the 6-month treatment with MLC901 did not result in a statistically significant difference with placebo for CNS-VS measurement of cognitive domains in individuals with mild TBI, the study showed a clinically and statistically significant improvement in all clinical scales assessed by the investigators. ClinicalTrials.gov identifier NCT04861688.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Adults / Aged / Anxiety / Biology and Life Sciences / Brain / Brain Concussion - complications / Brain Concussion - drug therapy / Care and treatment / Causes of / Clinical trials / Cognition disorders / Cognitive ability / Cognitive Dysfunction - drug therapy / Cognitive Dysfunction - etiology / Complications / Concussion / Double-Blind Method / Drugs, Chinese Herbal / Effectiveness / Evaluation / Executive function / Female / Head injuries / Health services / Herbal medicine / Humans / Impairment / Injuries / Male / Medicine and Health Sciences / Medicine, Botanic / Medicine, Herbal / Memory / Mental depression / Middle Aged / Neuropsychology / Patient outcomes / Placebos / Quality of Life / Questionnaires / Randomization / Research and Analysis Methods / Social Sciences / Statistical analysis / Traditional Chinese medicine / Traumatic brain injury / Treatment Outcome / Vital signs / World population / Young Adult