Effects of MLC601 on Early Vascular Events in Patients After Stroke

Chen, Christopher; Venketasubramanian, Narayanaswamy; Lee, Chun Fan; Wong, Ka Sing; Bousser, Marie‐Germaine; Investigators, Chimes Study; Philippines,; Navarro, Jose C.; Gan, Herminigildo H; Lao, Annabelle Y.; Baroque, Alejandro C.; Lokin, Johnny; Hiyadan, John Harold B; Sarfati, Ma Socorro F; Fangonillo, Randolph John; Ambasing, Neil; Chúa, Carlos; Jose, Ma. Cristina San; Advincula, Joel; Berame, Eli John; Cañete, Maria Teresa A.; Singapore,; Young, Sherry; Mamauag, Marlie Jane; Tay, San San; Pande, Shrikant D; Umapathi, Thirugnanam; Singh, Rajinder; Chang, Hui Meng; Silva, Deidre Anne De; Chan, Bernard P.L.; Sharma, Vijay K.; Luen, Teoh Hock; Thailand,; Poungvarin, Niphon; Muengtaweepongsa, Sombat; Towanabut, Somchai; Suwanwela, Nijasri C.; Chotickanuchit, Songkram; Chankrachang, Siwaporn; Nitinun, Samart; Lanka, Sri; Silva, H. Asita de; Ranawake, Udaya A.; Wijekoon, Nalaka; Kong, Hong; Malaysia,; Eow, Gaik Bee

doi:10.1161/strokeaha.113.003226

Cited by 33 publications

(26 citation statements)

References 15 publications

(19 reference statements)

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“…We have also previously shown a reduction in early vascular events with MLC601 treatment for 3 months [19]. In CHIMES-E, we noted consistently favorable treatment effect for all assessment time points but the largest effect was seen at 6 months with a gradual decline at 24 months; however, no difference in rates of vascular events was observed.…”

Section: Discussionsupporting

confidence: 71%

“…We have previously demonstrated that post-stroke use of concomitant secondary prevention treatments and rehabilitation in CHIMES were high and similar between the two treatment groups [19]. …”

Section: Methodsmentioning

confidence: 99%

“…More recently, MLC601 was evaluated in the CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) study, a large international, multicenter, randomized, double-blind, placebo-controlled clinical trial, which showed a statistically nonsignificant effect of MLC601 at 3 months among subjects with cerebral infarction in the preceding 72 h (ClinicalTrials.gov: NCT00554723) [17,18,19]. It was among the first to investigate the use of a product from natural substances that reduced the disability after an acute stroke in a rigorous manner to achieve a balance between ‘uncritical enthusiasm' and ‘uninformed skepticism'.…”

Section: Introductionmentioning

confidence: 99%

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CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy

et al. 2015

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Background: The CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) study was an international randomized double-blind placebo-controlled trial of MLC601 (NeuroAiD) in subjects with cerebral infarction of intermediate severity within 72 h. CHIMES-E (Extension) aimed at evaluating the effects of the initial 3-month treatment with MLC601 on long-term outcome for up to 2 years. Methods: All subjects randomized in CHIMES were eligible for CHIMES-E. Inclusion criteria for CHIMES were age ≥18, baseline National Institute of Health Stroke Scale of 6-14, and pre-stroke modified Rankin Scale (mRS) ≤1. Initial CHIMES treatment allocation blinding was maintained, although no further study treatment was provided in CHIMES-E. Subjects received standard care and rehabilitation as prescribed by the treating physician. mRS, Barthel Index (BI), and occurrence of medical events were ascertained at months 6, 12, 18, and 24. The primary outcome was mRS at 24 months. Secondary outcomes were mRS and BI at other time points. Results: CHIMES-E included 880 subjects (mean age 61.8 ± 11.3; 36% women). Adjusted OR for mRS ordinal analysis was 1.08 (95% CI 0.85-1.37, p = 0.543) and mRS dichotomy ≤1 was 1.29 (95% CI 0.96-1.74, p = 0.093) at 24 months. However, the treatment effect was significantly in favor of MLC601 for mRS dichotomy ≤1 at 6 months (OR 1.49, 95% CI 1.11-2.01, p = 0.008), 12 months (OR 1.41, 95% CI 1.05-1.90, p = 0.023), and 18 months (OR 1.36, 95% CI 1.01-1.83, p = 0.045), and for BI dichotomy ≥95 at 6 months (OR 1.55, 95% CI 1.14-2.10, p = 0.005) but not at other time points. Subgroup analyses showed no treatment heterogeneity. Rates of death and occurrence of vascular and other medical events were similar between groups. Conclusions: While the benefits of a 3-month treatment with MLC601 did not reach statistical significance for the primary endpoint at 2 years, the odds of functional independence defined as mRS ≤1 was significantly increased at 6 months and persisted up to 18 months after a stroke.

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Section: Discussionsupporting

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy

et al. 2015

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“…Clinical studies to assess the benefit and safety of MLC601 in stroke patients using different clinical outcome have been performed [10][11][12][13][14][15][16][17][18] . The Chinese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) trial, which compared MLC601 with placebo in 1,099 patients with acute ischemic stroke of intermediate severity, reported a reduction in early recurrent vascular events and vascular deaths in post-stroke patients [11,19,20] . Interestingly, in the Philippine cohort of the CHIMES trial, which included more patients with predictors of poorer prognosis, functional and neurological outcomes were improved in favor of MLC601 [15] .…”

Section: Introductionmentioning

confidence: 99%

MLC901 Favors Angiogenesis and Associated Recovery after Ischemic Stroke in Mice

Gandin

Widmann²,

Lazdunski³

et al. 2016

Cerebrovasc Dis

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Background: There is increasing evidence that angiogenesis, through new blood vessel formation, results in improved collateral circulation and may impact the long-term recovery of patients. In this study, we first investigated the preventive action of a 5-week pretreatment of MLC901, an herbal extract preparation derived from Chinese medicine, against the deleterious effects of ischemic stroke and its effects on angiogenesis in a model of focal ischemia in mice. Methods: The stroke model was induced by 60 min of middle cerebral artery occlusion followed by reperfusion. MLC901 was administered in the drinking water of animals (6 g/l) for 5 weeks before ischemia and then during reperfusion. Results: MLC901 treatment increased the survival rate, reduced the cerebral infarct area and attenuated the blood brain barrier leakage as well as the neurologic dysfunction following ischemia and reperfusion. We provide evidence that MLC901 enhances endothelial cell proliferation and angiogenesis by increasing the number of neocortical vessels in the infarcted area. MLC901 regulates the expression of hypoxic inducible factor 1α and its downstream targets such as vascular endothelial growth factor and angiopoietins 1 and 2. This work also shows that erythropoietin is an important player in the enhancement of angiogenesis by MLC901. Conclusions: These results demonstrate therapeutic properties of MLC901, in addition to those previously described, in stimulating revascularization, neuroprotection and repair of the neurovascular unit after ischemic stroke.

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“…The updated meta-analysis showed a pooled odds ratio in favor of NeuroAiD [27]. Furthermore, treatment with NeuroAiD was associated with a reduction in risk of early vascular events after a stroke [30]. More recently, the extension study of this randomized, placebo-controlled, double blind trial has provided evidence of its benefit on long-term functional outcome persisting over time up to 18 months after a stroke with an excellent safety profile [31].…”

Section: Introductionmentioning

confidence: 99%

Spinal Cord Injury—Assessing Tolerability and Use of Combined Rehabilitation and NeuroAiD (SATURN Study): Protocol of An Exploratory Study In Assessing the Safety and Efficacy of NeuroAiD Amongst People Who Sustain Severe Spinal Cord Injury

Kumar¹,

Htwe²,

Baharudin³

et al. 2016

JMIR Res Protoc

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BackgroundSpinal cord injury (SCI) is a devastating condition with limited therapeutic options despite decades of research. Current treatment options include use of steroids, surgery, and rehabilitation. Nevertheless, many patients with SCI remain disabled. MLC601 (NeuroAiD), a combination of natural products, has been shown to be safe and to aid neurological recovery after brain injuries and may have a potential role in improving recovery after SCI.ObjectiveThe aim of this study is to evaluate the safety and efficacy of NeuroAiD amongst people who sustain SCI in the study setting.MethodsSpinal Cord Injury—Assessing Tolerability and Use of Combined Rehabilitation and NeuroAiD (SATURN) is a prospective cohort study of patients with moderately severe to severe SCI, defined as American Spinal Injury Association (ASIA) Impairment Scale (AIS) A and B. These patients will be treated with open-label NeuroAiD for 6 months in addition to standard care and followed for 24 months. Anonymized data will be prospectively collected at baseline and months 1, 3, 6, 12, 18, and 24 and will include information on demographics; main diagnostics; and neurological and functional state assessed by the Spinal Cord Independence Measure, ASIA—International Standard for Neurological Classification Spinal Cord Injury, and Short Form (SF-8) Health Survey. In addition, NeuroAiD treatment, compliance, concomitant therapies, and side effects, if any, will be collected. Investigators will use a secured online system for data entry. The study is approved by the ethics committee of Hospital University Kebangsaan Malaysia.ResultsThe coprimary endpoints are safety, AIS grade, and improvement in ASIA motor score at 6 months. Secondary endpoints are AIS grade, ASIA motor scores and sensory scores, Spinal Cord Independence Measure (SCIM), SF-8 Health Survey, and compliance at other time points.ConclusionsSATURN investigates the promising role of NeuroAiD in SCI especially given its excellent safety profile. We described here the protocol and online data collection tool we will use for this prospective cohort study. The selection of moderately severe to severe SCI provides an opportunity to investigate the role of NeuroAiD in addition to standard rehabilitation in patients with poor prognosis. The results will provide important information on the feasibility of conducting larger controlled trials to improve long-term outcome of patients with SCI.Trial RegistrationClinicaltrials.gov NCT02537899; https://clinicaltrials.gov/ct2/show/NCT02537899 (Archived by WebCite at http://www.webcitation.org/6m2pncVTG)

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Effects of MLC601 on Early Vascular Events in Patients After Stroke

Cited by 33 publications

References 15 publications

CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy

CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy

MLC901 Favors Angiogenesis and Associated Recovery after Ischemic Stroke in Mice

Spinal Cord Injury—Assessing Tolerability and Use of Combined Rehabilitation and NeuroAiD (SATURN Study): Protocol of An Exploratory Study In Assessing the Safety and Efficacy of NeuroAiD Amongst People Who Sustain Severe Spinal Cord Injury

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