Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post-Stroke Recovery: The CHIMES and CHIMES-E Studies

Abstract

Background and Purpose: MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. Methods: Data from the CHInese Medicine NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. Results: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8 ± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0–1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. Conclusions: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments.

Predictors of Neurological and Functional Recovery in Patients with Moderate to Severe Ischemic Stroke: The EPICA Study

“…Subanalyses of the large clinical trial showed larger treatment effects among patients with predictors of poor outcome, including worse baseline NIHSS, likely because they had more potential to benefit from treatment [26,34,35]. A more recent analysis demonstrated that among patients who perform persistent rehabilitation, the use of this dietary supplement increased 10 Stroke Research and Treatment the rate of functional independence at 3 months and sustained over 2 years compared to rehabilitation alone [36]. This benefit was not seen among patients who did not consistently perform rehabilitation, suggesting that neurorestorative therapies work better when the brain is primed by rehabilitation.…”

NeuroAid II (MLC901) in Haemorrhagic Stroke

“…It was first registered by the Sino Food and Drug Administration in 2001 after initial clinical trials done in China reported that MLC601 has improved functional outcome and recovery from post-stroke disability [7]. Over the next few years, many studies have reported on the benefits of MLC601, including a double-blind, placebo-controlled pilot study to investigate the potential efficacy of MLC601 in enhancing post-stroke recovery, which indicated that some positive trends were observed in the MLC601 group, and thus it may be useful for post-stroke rehabilitation [3, 4, 8, 9]. With regards to its safety profile, long-term laboratory data (biochemical, haematological, or electrocardiogram tests) confirms safety of MLC601 in acute stroke patients receiving a 3-month treatment, with no risk of increased haemorrhage [10, 11].…”

The Traditional Chinese Medicine MLC901 inhibits inflammation processes after focal cerebral ischemia

“…Accumulating evidence from animal studies 36–40,54 and clinical trials 17,22,23,26,28,29,31,55 indicates that MLC601 and its derivative product MLC901 probably represent a promising therapeutic strategy for brain injuries, and particularly for stroke treatment. The molecular and cellular mechanisms associated with the beneficial effects of this TCM in cellular and animal models of stroke are multifaceted.…”