Efficacy of Chinese Traditional Medicine Smart Soup in Cognition and Behavior Regulation in Alzheimer's Disease

Study Overview
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Brief Summary
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It is a prospective interventional randomized controlled single center trial. The goal of the trial is to evaluate the efficacy of smart soup on cognition, behavior, biomarkers and safety in Alzheimer's disease (aMCI and dementia).

Detailed Description
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Alzheimer's disease (AD) is the most common cause of dementia and places a heavy burden on patients, families, society and healthcare. The drugs that have been marketed worldwide for the treatment of AD so far can only delay but not reverse the course of the disease, and the current drug development is all directed at a single target, while the onset of AD is the result of a combination of multiple factors, which is an important reason why so many drugs have faltered. The investigators need to find new multi-target intervention pathways from another perspective. The advantage of Chinese medicine is multi-target and multi-factor regulation, which has advantages in treating complex diseases. The combination of ancient smart soup with donepezil was able to significantly improve the cognitive function in demented animals. Smart Soup is prepared from three herbs: Rhizoma Acori Tatarinowii, Poria cum Radix Pini, Radix Polygalae. These three herbs are each 15 grams and ground into a very fine powder. This approach reduced the formation of characteristic pathological changes at the pathological level, therefore, the combination of ancient Chinese medicine formulae with modern medical treatment may bring new hope to the treatment of demented patients. The main design of this study are following: Patients over 40 years of age and eligible for NIA-AA 2011 probable AD and probable MCI were included in this study and were divided into 6 groups of 30 patients each. Group I AD patients were given donepezil 10 mg, memantine 20 mg and smart soup, group II AD patients were given donepezil 10 mg, memantine 20 mg and placebo; group III AD patients were given donepezil 10 mg and smart soup, group IV AD patients were given donepezil 10 mg and placebo; group V mild cognitive impairment (MCI) patients were given smart soup, and group VI MCI patients were given placebo. Evaluations were set before enrollment, every three months till one year and the evaluators were single-blind. The scales involved in the evaluation of cognitive function and quality of life, sleep condition, and emotional behavior included ADAS-cog, MMSE, CDR, ADL, CMAI, NPI, and EQ-5D, which were evaluated five times. MRI, EEG, blood oxidative stress indicators, and biological markers were collected at the same time at enrollment and at the end of the study. Genotype collection was completed at enrollment. Safety was also evaluated with monthly testing of ECG, routine blood, liver and kidney function, urinary routine, and recording of side effects.

Official Title
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Efficacy of Chinese Traditional Medicine Smart Soup in Cognition and Behavior Regulation in Alzheimer's Disease

Conditions
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Alzheimer Disease, Mild Cognitive Impairment

Intervention / Treatment
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* Drug: smart soup
* Drug: Donepezil
* Drug: Memantine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NIA-AA 2011 AD probable Alzheimer's disease, mild to moderate, stable use donepezil 10mg/d for 3 months NIA-AA 2011 AD probable Alzheimer's disease, severe, stable use donepezil 10mg/d and memantine 20mg/d for 3 months NIA-AA 2011 MCI probable criteria stable care giver Traditional Chinese medicine diagnosis: pixu tanzhuo Exclusion Criteria: Severe systemic disease (heart, liver ,kidney function failure) contradictions of MRI examination

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 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
Interventional Model Description: Patients were divided into 6 groups according to the enrollment criteria, with 30 cases in each group. Group I AD patients were given donepezil 10 mg, memantine 20 mg and smart soup, group II AD patients were given donepezil 10 mg, memantine 20 mg and placebo; group III AD patients were given donepezil 10 mg and smart soup, group IV AD patients were given donepezil 10 mg and and placebo; group V MCI patients were given smart soup, and group VI MCI patients were given placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group I severe AD<br>Patients over 40 years of age and eligible for NIA-AA 2011 probable severe AD will be given donepezil 10 mg, memantine 20 mg and smart soup | Drug: smart soup<br>* Severe AD, mild or moderate AD and MCI will be given smart soup<br>* Other names: traditional chinese medicine;Drug: Donepezil<br>* Severe AD and mild or moderate AD will be given donepezil<br>* Other names: donepezil pill;Drug: Memantine<br>* Severe AD will be given memantine<br>* Other names: Memantine Pill;|
| Sham Comparator: Group II severe AD<br>Patients over 40 years of age and eligible for NIA-AA 2011 probable severe AD will be given donepezil 10 mg, memantine 20 mg and placebo | Drug: Donepezil<br>* Severe AD and mild or moderate AD will be given donepezil<br>* Other names: donepezil pill;Drug: Memantine<br>* Severe AD will be given memantine<br>* Other names: Memantine Pill;Drug: Placebo<br>* patients with MCI will be given placebo<br>|
| Active Comparator: Group III Mild or moderate AD<br>Patients over 40 years of age and eligible for NIA-AA 2011 probable mild or moderate AD will be given donepezil 10 mg and smart soup | Drug: smart soup<br>* Severe AD, mild or moderate AD and MCI will be given smart soup<br>* Other names: traditional chinese medicine;Drug: Donepezil<br>* Severe AD and mild or moderate AD will be given donepezil<br>* Other names: donepezil pill;|
| Sham Comparator: Group IV Mild or moderate AD<br>Patients over 40 years of age and eligible for NIA-AA 2011 probable mild or moderate AD will be given donepezil 10 mg and placebo | Drug: Donepezil<br>* Severe AD and mild or moderate AD will be given donepezil<br>* Other names: donepezil pill;Drug: Placebo<br>* patients with MCI will be given placebo<br>|
| Active Comparator: Group V MCI<br>Patients over 40 years of age and eligible for NIA-AA 2011 probable MCI will be given smart soup | Drug: smart soup<br>* Severe AD, mild or moderate AD and MCI will be given smart soup<br>* Other names: traditional chinese medicine;|
| Sham Comparator: Group VI MCI<br>Patients over 40 years of age and eligible for NIA-AA 2011 probable MCI will be given placebo | Drug: Placebo<br>* patients with MCI will be given placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of cognitive screening | Using the neuropsychological scale, mini-mental state examination (MMSE,0-30), to assess every three months after trial entry | Through study completion, an average of 1 years | 
| Changes of comprehensive cognitive assessment | Use the neuropsychological scales, Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog 0-75)， to assess every three months after trial entry | Through study completion, an average of 1 years | 
| Changes in the degree of dementia | Use the neuropsychological scales, CDR(0-3), to assess every three months after trial entry | Through study completion, an average of 1 years | 
| Changes in behavior | Use the Cohen-Mansfield Agitation Inventory (CMAI，29-203) to assess every three months after trial entry | Through study completion, an average of 1 years | 
| Changes in Psychiatric symptoms | Use the Neuropsychiatric Index (NPI) to assess every three months after trial entry | Through study completion, an average of 1 years | 
| Changes of daily living skills | Use Activity of Daily Living Scale（ADL，20-80）to assess every three months after trial entry | Through study completion, an average of 1 years | 
| Changes in health status | Use EuroQoL 5-dimension (EQ-5D,0-100) to assess every three months after trial entry | Through study completion, an average of 1 years | 
| Tau and Beta-amyloid biomarkers in CSF and plasma | Concentration ( pg/mL) of beta-amyloid, tau and phospho-tau in cerebrospinal fluid (CSF) and plasma of patients with dementia and controls | Through study completion, an average of 1 years | 
| Magnetic resonance imaging and Electroencephalogram（EEG） | Evaluate the imaging and EEG changes of dementia patients. Specifically, EEG can be used to monitor the activity of brain waves in different parts of the cerebral cortex (e.g. power in alpha band, distribution and power of slow theta/delta waves etc.) | Through study completion, an average of 1 years | 
| Oxidative stress markers in blood | Concentration of Dopamine in blood of patients with dementia and controls | Through study completion, an average of 1 years | 
| Alterations of neurotransmitters in the blood | Concentration (ng/ml) of 5-hydroxy tryptamine (HT) in blood of patients with dementia and controls | Through study completion, an average of 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, Traditional Chinese Medicine, Smart soup