NeuroAiD: Clinical data in post-stroke recovery

• Functional outcome benefits at 3 months

• Benefits assessed over time at 6 months and beyond

• Motor functions recovery

• Clinical evidences in other neurological conditions

• Impact on early cardiovascular events and deaths after a stroke

Functional Outcome Improvement

With benefits observed as early as 3 months

 

~65% increase in odds of achieving independence among post-acute patients with established moderately severe deficits

A meta-analysis of four clinical trials pooling data in patients having initiated a 3-month course with NeuroAiD from 48h to 6 months after stroke onset has shown a high level of independence recovery:

  • 63% increase in odds of achieving independence with NeuroAiD

*Post-acute patients, consistent with previous trials

Chen C, et al. Chinese medicine Neuroaid efficacy on stroke recovery – A double-blind, placebo-controlled, randomized study. Stroke 2013; 44: 2093-2100.

The CHIMES study

The CHIMES study is an investigator-initiated multicenter study, placebo-controlled, double-blind, and parallel groups, having recruited 1100 subjects.

The CHIMES study is the largest clinical trial on the use of natural product in acute stroke.

The objective of the study was to measure the efficacy of NeuroAiD in subjects who experienced an ischemic stroke of intermediate severity in the preceding 72 hours. CHIMES was conducted by neurologists experienced in stroke management and uses standard neurologist efficacy endpoint, i.e., modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), Barthel index and Mini Mental State Examination (MMSE).

This multicenter trial was conducted in the Asia Pacific region, with the participation of international experts from France, Asia and Australia sitting in the Data Safety Monitoring Board. In Singapore, this study was fully sponsored and supported by the National Medical Research Council (NMRC) Ministry of Health.

Sub-analyses were performed on CHIMES database in patients with challenging prognosis and predictors of poorer outcomes. These sub-analyses have shown statistically significant treatment effect in favor of NeuroAiD.

68% increase in odds of achieving independence in patients included with more predictors of poorer prognosis (subjects included over 48h after stoke onset and subjects with more severe stroke: NIHSS from 10 to 14).

Navarro J, et al. Baseline characteristics and treatment response of patients from the Philippines in the CHIMES study. International Journal of Stroke 2014;9:102-105.

• NeuroAiD significantly increases the odds of achieving functional independence at 3 months of treatment in patients with 2 or more predictors of poorer outcomes, especially moderately severe stroke and sub-acute stage patients with confirmed impairments (stroke onset to treatment >48h).

Chankrachang S, et al. Prognostic Factors and Treatment Effect in the CHIMES Study. Journal of Stroke and Cerebrovascular Diseases 2015;24(4):823-827.

Sustaining Stroke Recovery
Persistence of benefits over time

~50% increase in odds of achieving functional independence at 6 months

An initial 3-month course with NeuroAiD significantly increases odds of achieving functional independence (mRS 0-1) after a stroke by ~50% at 6 months in overall population.

& these benefits are persisting over time.

* Adjusted for age, sex, stroke onset to study treatment, baseline NIHSS and pre-stroke mRS

Venketasubramanian N, et al. CHInese medicine NeuroAiD efficacy on stroke recovery – Extension study (CHIMES-E): A multicenter study of long-term efficacy. Cerebrovascular Diseases 2015;39:309-318.

All these results were consistent at various time points and seen on 2 indices, i.e. mRS dichotomy 0-1 and Barthel Index (BI).

The CHIMES Extension study

In April 2015, CHIMES-E study results have been published in Cerebrovascular Diseases and released at ESOC (European Stroke Conference Organization) in Glasgow and at ESC (European Stroke Conference) in Vienna. CHIMES-E is the CHIMES Extension study and provides encouraging results in achieving functional independence over the long term with a follow-up of 24 months of the patients included in CHIMES (recruited within 72 hours after ischemic stroke onset and initiated a 3-month course of NeuroAiD vs Placebo).

The absolute benefit of achieving an independent functional outcome (mRS ≤1)

  • 80 per 1000 treated patients at 6 months
  • 71 per 1000 treated patients at 12 months
  • 64 per 1000 treated patients at 18 months
  • 53 per 1000 treated patients at 24 months

Adapted from Venketasubramanian N, et al. Cerebrovascular Diseases 2015

NeuroAiD was safe, well-tolerated during the 3-month treatment and the safety profile remains excellent up to 24 months with no delayed adverse event.

The long term effect of NeuroAiD with a 3-month course may justify considering an extension of the treatment duration, beyond 3 months.

Early Vascular Events reduction

A post-hoc analysis of the CHIMES Study was performed to investigate the effect of NeuroAiD on the occurrence of early vascular events defined as a composite of recurrent stroke, acute coronary syndrome, and vascular death within 3 months after stroke onset.

A statistically significant reduction in the risk of vascular events and/or vascular death by half was observed in the first three months after a stroke.

Chen C, et al. Effects of MLC601 on early vascular events in patients after stroke: The CHIMES study. Stroke 2013b;44:3580-3583.

  • Equivalent to 27 fewer patients suffering an early vascular event per 1000 patients treated over 3 months.
  • The benefit is in addition to the benefits gained from secondary prevention standard treatment.
  • The reduction was seen as early as the first two weeks after initiation of treatment: it supports the value of starting NeuroAiD as early as possible.
  • No additional bleeding risk even as add-on to antiplatelet agents. There was no increase in bleeding and non-vascular death, confirming the excellent safety profile of NeuroAiD. This finding is consistent with the pleotropic mechanisms of action of NeuroAiD.

Avoiding early occurrence of vascular events or death is a major added- value allowing the continuation of the recovery phase.

Motor Functions

NeuroAiD improves motor recovery by an additional 12 points on Fugl-Meyer scale

This study provides positive results for NeuroAiD in motor recovery. Patients on NeuroAiD showed significantly better motor recovery than patients on placebo. This improvement was mostly manifested after 4 weeks from start of treatment and developed more during 3 months with 12 additional points on FMA score in favor of NeuroAiD compared to placebo at 3 months.

Harandi AA, et al. Safety and efficacy of MLC601 in Iranian patients after stroke: A double-blind, placebo-controlled clinical trial. Stroke Research and Treatment 2011;72163.

Motor Recovery study

This double-blind placebo-controlled study included 150 subjects within 1 month after stroke onset treated with a 3-month course of NeuroAiD or placebo. Motor recovery was assessed by Fugl-Meyer Assessment scale (maximum score 100 points) every month for 3 months.

Other neurological conditions

Visual impairments

NeuroAiD supports recovery of visual deficits

After a stroke, the brain impairment results into a disruption of the information processing and transmission through the central nervous system. This can lead to visual impairments, such as double vision, fluctuating vision, visual field defects, visual acuity problems, hemianopsia, eye movement problems, and strabismus.

Relative reduction of right and left visual field defects after treatment was higher with NeuroAiD (45%) than with Piracetam (32%).*

Ghandehari K, et al. NeuroAiD (MLC601) versus Piracetam in the recovery of post-infarct homonymous hemianopsia. Neural Regeneration Research 2011;6(6):418-422.

Visual Impairment Study

This study compared 40 patients with pure homonymous hemianopsia from ischemic stroke, recruited within one week of onset and treated with either NeuroAiD or piracetam for 3 months. It showed that patients on NeuroAiD gained back more of their visual field at 3 months compared to control.

Neurosurgical pathologies

Pharmacological research confirmed positive effects of NeuroAiD on neuroplasticity and neuroprotection in neurosurgical pathologies which support its use in hemorrhagic stroke and brain injury conditions.

The multimodal mechanism of NeuroAiD and timelines of its pharmacological effects have also been shown in an animal model of Traumatic Brain Injury. All the results of the pre-clinical study showed neuroprotective and neurorestorative effects attributable to NeuroAiD.

There are no published clinical trials on these conditions, one trial is currently ongoing in New Zealand. There are several patients series / case report are available. Contact us if you would like to find out more

NeuroAiD reduces lesion volume and increases cell survival

Coronal TTC-stained brain sections 24h after TBI
In rat treated with MLC901, administered 2h after TBI, cortical infarcts indicated by the white area were strongly reduced.

Quintard H, et al. MLC 901, a Traditional Chinese Medicine induces neuroprotective and neuroregenerative benefits after traumatic brain injury in rats. Neuroscience 2014;277:72–86

Alzheimer’s disease

Latest research supports positive role of NeuroAiD in stroke prevention as well as in neurodegenerative disease which will have to be further investigated. A first study published in 2013 reports good tolerability and promising effects in Alzheimer patients over 18 months of treatment.

NeuroAiD is well-tolerated and promising in patients with Alzheimer’s dementia:

Subjects with mild to moderate Alzheimer’s dementia who failed or experienced adverse effects on rivastigmine (n=122).Measures and analyses showed a significant improvement in cognitive function as measures by Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) and Mini-Mental State Examination (MMSE) in the first 6 months.

Harandi et al., British Journal of Medicine & Medical Research 2013

Adverse effects during previous treatment with rivastigmine and during treatment with NeuroAiDTM (MLC601).

Few adverse effects have been reported with NeuroAiD compared to previous treatment with Rivastigmine.

Harandi et al., British Journal of Medicine & Medical Research 2013

NeuroAiD is a possible modulator of Amyloid Precursor Protein (APP) processing, increasing the release of sAPPα and in the meantime decreasing full-length APP levels.

With this activity, NeuroAiD appears to favor
the non-pathogen pathway for the APP.

Lim et al., Cerebrovascular Diseases 2013