NEURoaid II (MLC 901) Assessment in Cognitively Impaired Not Demented Subjects

Study Overview
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Brief Summary
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Patients who have suffered from stroke may develop problems with thinking. Moreover, such patients have a high risk of becoming demented, more dependent or dying. Therefore, further studies are urgently needed to find effective and safe treatments. Neuroaid is a Traditional Chinese Medicine which has been shown to stimulate growth of brain cells and connections in animals. Neuroaid may improve blood flow in the brain and functional recovery after stroke in patients. Neuroaid-II is a simplified formula with only the main 9 herbal ingredients of the original formula and no animal ingredients. The NEURoaid II (MLC 901) assessment in cognitively Impaired not demented subjects: a pilot double blind, placebo-controlled randomized Trial on Efficacy and Safety (NEURITES) Study is a 24-week, early phase trial of Neuroaid-II in patients who have thinking problems after stroke. The study aims to investigate the effectiveness of the study drug in improving cognitive performance. The safety of the study drug will be closely monitored using adverse events, laboratory tests and vital signs. The trial is important as it aims to set new standards for the scientific evaluation of Asian Traditional Medicine for integration into standard medicine practice. It may potentially establish a novel therapeutic approach for improving cognition after stroke.

Detailed Description
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A substantial proportion of patients after non-disabling stroke are cognitively impaired compared to aged and education matched community dwelling controls. Moreover, post-stroke patients who have vascular cognitive impairment not dementia (VCIND) of moderate severity have a high risk of incident dementia, dependency and death. Further studies are urgently needed to demonstrate effective cognition enhancing therapies in VCIND given the absence of evidence based treatment options. Neuroaid is a Traditional Chinese Medicine which has been shown to induce neurogenesis, promote cell proliferation and stimulate development of axonal and dendritic networks in animal models. Neuroaid may improve functional recovery after stroke in patients. Neuroaid-II is a simplified formulation with only 9 herbal and no animal ingredients. The NEURoaid II (MLC 901) assessment in cognitively Impaired not demented subjects: a pilot double blind, placebo-controlled randomized Trial on Efficacy and Safety (NEURITES) Study is a 24-week Phase II study. The primary outcome is executive function as measured by the Verbal Fluency test. Secondary outcomes include cognitive measures such as the ADAS-Cog, MoCA, MMSE and a Cognitive Battery; Activities of Daily Living as measured by the ADCS-ADL scale; behaviour as measured by the Neuropsychiatric Inventory and depression as measured by the Geriatric Depression Scale and Beck Depression Scale. Safety and tolerability will be assessed using adverse events, laboratory tests, and vital signs. The trial is important for translational medicine in Singapore through setting new standards for systematic evaluation of Traditional Medicine for integration into standard medicine practice

Official Title
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NEURoaid II (MLC 901) Assessment in Cognitively Impaired Not Demented Subjects : a Pilot Double Blind, Placebo-controlled Randomized Trial on Efficacy and Safety (NEURITES) Study

Conditions
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Cognitive Impairment

Intervention / Treatment
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* Drug: MLC901
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients Aged 55 to 85, living with a caregiver, Modified Rankin score <=3. Diagnosis of CIND due to cerebrovascular disease. Cognitive impairment documented by neuropsychological evaluation within 12 months of index stroke/TIA. Not demented by DSM-IV criteria Written informed consent by subject Exclusion Criteria: Advanced, severe, and unstable disease of any type that may interfere with the efficacy evaluations or put the subject at special risk. DSM IV current diagnosis of dementia or major depression (patients may be included if currently being treated on an antidepressant and stabilized after 3 months). A disability that may prevent the subject from completing all study requirements (e.g. blindness, deafness, severe language difficulty). Ingestion of any of the following : an investigational drug in the past four weeks, a drug or treatment known to cause major organ system toxicity during the past four weeks, acetylcholinesterase inhibitors or memantine in the past 3 months

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MLC901<br>Brand: Neuroaid II. Dosage: 2 capsules 3 times a a day | Drug: MLC901<br>* 24 weeks intervention with orally MLC901. 2 capsules 3 times a day<br>* Other names: NeuroaidII (MLC901);|
| Placebo Comparator: placebo<br>MLC901 matching placebo made by the same manufacturer for this study dosage: 2 capsules 3 times a day. | Drug: Placebo<br>* 24 weeks intervention with orally placebo. 2 capsules 3 times a day<br>* Other names: MLC901 matched Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative change on executive function | To evaluate the comparative change from baseline with MLC901 and placebo on executive function in patients with cognitive impairment not dementia due to cerebrovascular disease, as measured by: Verbal Fluency and Colour Trails Test 1 & 2 | Baseline to 24th week(24 week) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative change on cognitive function | To evaluate the comparative change from baseline with Neuroaid and placebo on cognitive function, as measured by: ADAS-Cog MoCA Cognitive Battery (Symbol Digits Modalities Test, Maze, Digit Cancellation Test, Clock Drawing Test, Visual Memory Test and Frontal Assessment Battery) | Baseline to 24th week(24 week) | 
| Effects on activities of daily living | To evaluate the effects of Neuroaid on activities of daily living by : Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scale for mild cognitive impairment (MCI) | Baseline to 24th week(24 week) | 
| Effects on behaviour | To evaluate the effects of Neuroaid on behaviour by : Neuropsychiatric Inventory (NPI) | Baseline to 24th week(24 week) | 
| Effects on depression | To evaluate the effects of Neuroaid on depression by : Geriatric Depression Scale (GDS) | 24 week | 
| Adverse events, laboratory tests, and vital signs. | To evaluate the safety and tolerability of ML901 for 24 weeks of treatment, in comparison with placebo. Safety will be assessed using adverse events, laboratory tests, and vital signs. | Baseline to 24th week(24 week) |