Dr. Siwaporn Chankrachang
Chiangmai Hospital

Dr. Samart Nitinum
Kingmongkutla Hospital

Dr. Nijasri Suwanwela
Chulalongkorn Hospital

Dr. Sombat Mungtavepongsa
Thammasar Hospital

PHARMACOLOGY
Pharmacology research has established the neuroprotective and neurorestorative activities of NeuroAiD™ providing possible mechanisms for neurological recovery in post stroke patients.

Papers published in the journal Neuropharmacology in 2010 and 2011 established that NeuroAiD increases neurogenesis, neuroplasticity and neuroprotection and amplifies self repair and self protection of the brain.

NeuroAiD amplifies endogenous processes of neurogenesis and neuroplasticity:

• NeuroAiD stimulates the production of the Brain Derived Neurotrophic Factor (BDNF), which is known to promote neuroplasticity
• NeuroAiD induces neurogenesis in rodent and human cells, and stimulates the development of new neuronal circuits by promoting cell proliferation and the development of dense axonal and dendritic networks by increasing the expression of BDNF and AKT

NeuroAiD amplifies a number of self defense processes in the brain:

• NeuroAiD prevents neuronal death in an in vitro model of excitotoxicity using primary cultures of cortical neurons exposed to glutamate.
• Another rodent model of global ischemia confirmed the positive effect of NeuroAiD in treating cognitive and motor deficits induced by global ischemia
  NeuroAiD used in post global ischemia protects neurons against ischemic injury in the CA1 region of the hippocampus which plays a critical role in memory
• It inhibits neuronal cell death, protects neurons against DNA fragmentation, stimulates pathways involved in neuroprotection such as phosphoryration of the AKT protein and reduces oxidative stress

The registration in China was supported by the results obtained from initial double-blind control randomized studies performed in China from 1999 to 2001 on 605 ischemic stroke patients at restoration stage. These studies evidenced NeuroAiD’s efficacy to improve stroke patients’ ability to recover even when started several weeks after the stroke onset. Given its unique profile in attending stroke patients’ needs with a very safe profile, NeuroAiD™ presents a strong opportunity to fill a gap in stroke patients’ treatment in the West.

Source
1. Neuroprotective and neuroproliferative activities of NeuroAiD (MLC601, MLC901), a Chinese medicine, in vitro and in vivo. Neuropharmacology. 2010




2. MLC901, a traditional Chinese medicine protects the brain against global ischemia. Neuropharmacology. 2011

605 ischemic stroke patients at a late stage (14 days-2months after the stroke onset ) were enrolled in these studies: 201 patients for the first trial and 405 patients for the second one.
Efficacy was assessed after one month of treatment. As per most of stroke trials, they consisted of measuring functional outcomes (independence ) and neurological deficit with standard scales these scales are akin to the mRS (modified Rankin Score) and National Institute of Health Stroke Scale (NIHSS), the standard stroke scales used presently in stroke clinical research.
The meta-analysis of these two studies showed an odd ratio of 2.4 (p=0.007) of reaching independence as well as a further reduction of 25% of motor deficits for subjects receiving Neuroaid vs subjects from the control group. These results have been peer reviewed and published recently in Stroke – click here to read the full paper.

Below is an abstract of the scientific paper written after completion of studies, this paper has undergone peer-review process and will be published in the Cerebrovascular Disease Journal.

Abstract:

Background and Objective: Previous studies on Danqi Piantan Jiaonang (DPJ), a traditional Chinese medicine, in stroke patients showed promising results. Our aim was to determine the safety of DPJ in normal subjects and stroke patients through a series of studies assessing its immediate and long-term effects, alone and in combination with aspirin, on hematological, hemostatic, and biochemical parameters.

Methods: We conducted three studies from December 2004 to May 2006. Study I was a case series which recruited 32 healthy volunteers who were given two oral doses of four DPJ capsules (0.4g/ capsule) six hours apart. Study II was a randomized controlled trial of 22 healthy volunteers to receive either one oral dose of aspirin 300 mg alone or a combination of one dose of aspirin 300 mg and two doses of four DPJ capsules taken six hours apart. For both studies I and II, hemostatic parameters (PT, aPTT, Fibrinogen, platelet aggregation, D-Dimer) were tested at baseline, 2 hours, and 8 hours. Study III was a case series which recruited 10 patients with recent ischemic stroke (within 7 days) who were given four DPJ capsules taken orally three times a day for one month. Blood tests for hemostatic, hematological (complete blood count), and biochemical parameters (glucose, creatinine, ALT, AST, C-reative protein) were performed at baseline, 1 week, and 4 weeks.

Results: Apart from the expected changes in platelet aggregation in subjects taking aspirin, no significant differences were detected in hemostatic parameters at baseline, 2 hours, and 8 hours after oral intake of DPJ alone or in combination with aspirin. Likewise, no significant differences were observed in hematological, hemostatic, and biochemical parameters at baseline, 1 week, and 4 weeks of oral intake of DPJ.

Conclusion: Danqi Piantan Jiaonang (NeuroAiD®) does not significantly modify hematological, hemostatic, and biochemical parameters in normal subjects and stroke patients.

-          Neuroaid in Stroke Recovery – European Neurology

• Clinical trials on 605 patients recruited between 2 weeks and 6 months after their stroke shows that subjects taking NeuroAiD™ are 2.4 times more likely to regain independence and achieve an average of 25% higher recovery in motor functions versus subjects receiving another well established traditional medicine.(Stroke 2009)




• A double blind placebo controlled clinical trial which was conducted on 150 subjects having suffered from stroke less than 3 months previously. NeuroAiDTMshowed a better motor recovery than placebo, and was safe as an add-on therapy to standard ischemic stroke medications, especially in severe and moderate cases.(Stroke Research and Treatment , 2011)




• Neuroaid triggers a significant increase of Cerebral Blood Flow velocity after 3 months treatment. These results, which was associated with a better functional outcome, suggested increased angiogenesis and microcirculation activity as mechanisms of recovery (European Journal of Internal Medicine, 2011)
• NeuroAiDTM may increase the recovery of vision deficits in post stroke Homonymous Hemianopsia patients. The patients in NeuroAiDTMgroup demonstrated a 50% increase in therapeutic effects as compared to the Piracetam group (Neuronal Regeneration Research, 2011)




• Case reports on 10 patients who received NeuroAiD after ischemic stroke onset confirmed on imaging recorded a variety of improvements (motor, gait, cognitive) (European Neurology 2009)




• In a double-blind, placebo-controlled, randomized phase II pilot study to investigate the potential efficacy of the traditional Chinese medicine NeuroAiD (MLC 601) in enhancing recovery after stroke (TIERS), treatment was initiated less than one month post ischemic stroke. NeuroAiD performed better in severe cases (+58% compared to the Placebo panel) and in best responders group (+39% better recovery than in placebo panel) (Cerebrovascular Disease, 2009)

Safety Profile
Neuroaid has well established safety profile. Several clinical trials have established its excellent tolerability both at acute and chronic stages;

• Biochemical, haematological and electrocardiogram tests demonstrated that NeuroAiD is as safe as a placebo for stroke patients receiving a 3- month treatment in a sub study of an ongoing randomized placebo controlled trial.Analysis of various physiological parameters demonstrates and confirms that NeuroAiD is safe in acute stage stroke patients – Cerebrovascular Diseases 2009




• NeuroAiD does not significantly affect hematological, hemostatis, and biochemical, in normal and stroke patients. Clinical parameters and expected effect of aspirin are not altered by co-administration of the drug even when started and maintained at the early stage of acute stroke. Cerebrovascular Diseases 2008


References:

1. Neuroprotective and neuroproliferative activities of NeuroAiD (MLC601, MLC901),
   a Chinese medicine, in vitro and in vivo. Neuropharmacology. 2010




2. MLC901, a traditional Chinese medicine protects the brain against global ischemia.
   Neuropharmacology. 2011




3. NeuroAiD, a traditional Chinese medicine, in post stroke recovery.Stroke. 2009




4. Safety and efficacy of MLC601 in Iranian patients after stroke: a double-blind, Placebo-controlled clinical trial.Stroke Research and Treatment. 2011




5. NeuroAiD in Stroke Recovery European Neurology. 2008




6. The effect of NeuroAiD™ (MLC601) on cerebral blood flow velocity in subjects’ post brain infarct in the middle cerebral artery territory.European Journal of Internal Medicine.2011




7. Case report on the use of MLC 601 (NeuroAiD) in neurosurgical pathologies.Poster presented at the World Stroke Congress in Seoul. 2010




8. NeuroAiD (MLC601) versus piracetam in the recovery of post-infarct homonymous hemianopsia. Neural Regeneration Research. 2011




9. A double-blind, placebo-controlled, randomized, multicenter study to investigate
   Chinese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES Study). International
   Journal of Stroke. 2009




10. Safety Profile of MLC601 (NeuroAiD ) in Acute Ischemic Stroke Patients: A Singaporean Substudy of the Chinese Medicine NeuroAiD Efficacy on Stroke Recovery Study. Cerebrovascular Diseases. 2010




11. NeuroAiD does not modify hemostasis, hematology, and biochemistry in normal subjects and stroke patients.Cerebrovascular Diseases. 2008.




12. A double-blind, placebo-controlled, randomized phase II pilot study to investigate the
    potential efficacy of the traditional Chinese medicine Neuroaid (MLC 601) in enhancing
    recovery after stroke (TIERS).Cerebrovascular Diseases. 2009
]]> http://chimes-society.org/chimes-trial/clinical-research/feed/ 0 http://chimes-society.org/chimes-trial/chimes-protocol/ http://chimes-society.org/chimes-trial/chimes-protocol/#comments Wed, 23 Sep 2009 09:03:19 +0000 admin http://webmaster/wp/?p=116 CHIMES protocol was published in March 2009 in the International Journal of Stroke click here to be redirected to the journal website

The protocol is also available on www.ClinicalTrials.gov under the identifier NCT00554723.

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Protocol Synopsis

Study Objective
To test the hypothesis that Neuroaid is superior to Placebo in reducing neurological deficit and improving functional outcome in patients with cerebral infarction of an intermediate range of severity (6 ≤ NIHSS ≤ 14).

Study Population
Potential subjects are screened for eligibility at baseline.

Inclusion criteria:
A subject will be eligible for inclusion in the trial only if all the following criteria apply at baseline:

• Subject is aged 18 years old and above




• Subject is on anti-platelet therapy




• Subject has a pre-stroke Modified Rankin Scale inferior or equal to 1




• A female subject is eligible to participate in the trial if she is of non childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal)




• Subjects or his/her legally acceptable representative is willing to provide written informed consent




• Subject has a cerebral infarction with compatible imaging using Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI)




• Time window is less than 72 hours after symptoms onset




• Subject has cerebral infarction with an intermediate severity range 6≤NIHSS≤14



Exclusion criteria:
A subject will not be eligible for inclusion in the trial if any of the following criteria apply at baseline:

• Subjects deemed unstable by investigator after thrombolysis treatment




• Subject has evidence of intra-cerebral hemorrhage on brain CT scan or MRI




• Subject has a rapidly improving neurological deficit




• Subject has definite indication for full-dose or long-term anticoagulation therapy




• Subject has other significant non-ischemic brain lesion which could affect function or disability




• Subject has co-existing systemic diseases which may affect assessment or follow-up such as terminal cancer, renal failure (creatinine >200umol/L if known), cirrhosis, severe dementia or psychosis.




• Subject has participated in another clinical trial within the last three months



The Study Endpoints are:

• Primary Efficacy Outcomes is the modified Rankin Scale grades at 3 months for all randomized subjects.




• Secondary Efficacy Outcomes are standard Western scales such as for stroke: NIHSS, mRS, Barthel index, mini-mental State Examination (MMSE).



Eligibility criteria have been chosen to allow most of the ischemic stroke patients to be included in the study and benefit from the TCM treatment.


Patient participation to the study will consist of a simple procedure:

• Recruitment: The investigator in charge of the trial determines whether the patient fits the criteria of inclusion and exclusion. Once eligibility is confirmed, the patient is offered to participate to the trial and is asked to sign a consent form.




• Assignment: The patient eligible is randomly assigned either to NeuroAiD or to a matched-placebo for 3 months.




• Initial assessment: On the first day of treatment, the doctors assess the patient neurological disability on 3 stroke standard scales used in western clinical trial methodology: NIHSS (neurological deficits), mRS (functional outcome) and MMSE (cognitive functions).




• Assessment at discharge from the hospital: When the patient leaves the hospital, the doctor will conduct a similar examination to assess the patient improvement.




• Assessment at 1 month: This assessment is performed by phone and assesses only patient autonomy (mRS).




• Assessment at 3 months: the patient recovery is assessed by investigators on the same three standards scales. Patient independence from any help, physical or verbal will also be measured by a fourth test called Barthel Index.




• As per standard clinical trial guidelines, the CHIMES Society has appointed a Data and Safety Monitoring Board that will provide an unbiased process through which the CHIMES study will be monitored and patient safety protected.
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