A Study to Evaluate the Efficacy and Safety of Brain Polypeptide Solution in Mild Alzheimer's Disease

Study Overview
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Brief Summary
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In recent years, reduced levels of brain-derived neurotrophic factor (BDNF) have been found in dementia patients. BDNF reduces amyloid precursor protein (APP) fragments via the Trk signaling pathway, and the expression of transgenic BDNF in animal models of Alzheimer's Disease（AD）shows a protective effect on neurodegeneration. A lot of researches have proved that brain hydrolysate injection can improve the level of BDNF in the brain. And oral brain peptide dietary supplements, which is also derived from brain proteolytic products, may also adjust and improve neuron metabolism, promote the formation of synapses, induce the differentiation of neurons, and protect nerve cells from ischemia and neurotoxin damage, reduce the risk of loss of cognitive function in the aging process. However, there are still no studies on dietary supplements derived from brain protein hydrolysates in China. Therefore, the investigators designed a randomized controlled double-blind study program to preliminarily evaluate the efficacy, safety and possible mechanism of brain polypeptide solution in improving the cognition of mild alzheimer's disease patients. The research is a prospective, multicenter, cohort study. 200 patients with mild alzheimer's disease will be selected and randomly divided into experimental group and control group according to the numerical random table. The experimental group will take the brain polypeptide solution 60ml per day and the control group was treated with the same package of placebo 60ml per day. The treatment regimen remained unchanged during the observation period. During the study period, safety index including blood and urine routine, liver and kidney function, coagulation index and clinical effect index about neuropsychological scales will be recorded.

Detailed Description
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The investigators design a prospective, multicenter, cohort study.200 patients with mild Alzheimer's disease will be selected and divided into brain polypeptide nutrient solution group (experimental group) and control group according to the numerical random table. The experimental group will take brain polypeptide solution 60ml per day, while the control group took placebo in the same package 60ml per day. The observation period is 84 days. And follow-up will take place at 42 and 84 days .The treatment regimen remained unchanged during the observation period. Safety indexes include blood and urine routine, liver and kidney function, coagulation index, etc. Screening indexes include syphilis antibody, HIV antibody, hepatitis b virus antibody, hepatitis c virus antibody, folic acid, vitamin B12, etc. Clinical outcome indicators include a number of scales to evaluate neurological and cognitive functions, such as the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog). Mechanism related indicators such as metabolomics was used to understand the possible differences in metabolic indicators. It is helpful to guide the use of brain polypeptide in Alzheimer's patients correctly .

Official Title
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A Multi-center, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy and Safety of Brain Polypeptide Solution in Improving Cognitive Function in Mild Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Dietary Supplement: brain polypeptide solution
* Other: same package of placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age range from 50 to 85 (including 50 and 85 years old), regardless of ethnic group or gender; The subjects should be able to complete the cognitive ability measurement and other tests specified in the protocol; meeting the criteria for likely Alzheimer's Disease （AD） dementia (2007) by National Institute of Neurological Disorders and Strokes - Alzheimer's Disease and Related Diseases Association（NINCDS-ADRDA）; patients with mild dementia: the total score of Mini-Mental State Examination (MMSE) : illiteracy ≤17 points, primary school ≤20 points, secondary school ≤22 points, university ≤23 points; Clinical Dementia Rating scale （CDR） = 1 point; the total score of the Hachinski Ischemic Score （HIS ）was < 4. Hamilton depression scale (17 items) total score ≤7 points; Brain MRI shows a high likelihood of AD; before enrollment, patients should take a stable dose of dementia drugs (such as donepezil 10mg) ≥8 weeks; the expected survival time is > 1 year; subjects should have a stable and reliable caregiver, or at least have frequent contact with the caregiver (at least 3 days per week and at least 2 hours per day), who will help patients participate in the whole study; Caregivers must accompany the subjects to the visit and assist in completing the relevant scale. Exclusion Criteria: refuse to sign the inform consent form; other causes of dementia: known vascular, central nervous system infection ,Parkinson's disease, traumatic brain dementia, other physical and chemical factors; serious body disease , intracranial space-occupying lesions, endocrine system disease, such as thyroid disease, and a lack of vitamin B12, folic acid, or any other known causes of dementia. central nervous system diseases (including stroke, optic neuromyelitis, Parkinson's disease, epilepsy, etc.); obvious positive signs of nervous system examination; psychotic patients, including schizophrenia or other disorders with bipolar disorder, major depression or delirium; uncontrolled hypertension or hypotension during screening: systolic blood pressure ≥180（millimetres of mercury ）mmHg or < 90mmhg, or diastolic blood pressure ≥120mmHg or < 60mmhg; unstable or severe diseases of the heart, lung, liver, kidney and hematopoietic system according to the judgment of the researchers; patients with incurable visual and auditory disorders that cannot complete neuropsychological tests and scales; female subjects who are positive in pregnancy test or breast-feeding and who cannot take effective contraceptive measures or have a birth plan; severe allergy, non-allergic drug reaction or multi-drug allergy history; participated in other clinical trials within 3 months before screening visit; taking any health care products related to brain and brain improvement currently and failing to keep the promise to stop using the above products; other conditions are unsuitable for participating in this study according to the judgement of researchers.

Ages Eligible for Study
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Minimum Age: 50 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>The experimental group will take the brain polypeptide solution . | Dietary Supplement: brain polypeptide solution<br>* The experimental group will take the brain polypeptide solution 60ml per day which contains nitrogen 90mg, soybean oil ,glycerin and soybean phospholipids in 84days.<br>|
| Placebo Comparator: Control group<br>The control group was treated with the same package of placebo . | Other: same package of placebo<br>* The control group was treated with the same package of placebo 60ml per day which contains soybean oil ,glycerin and soybean phospholipids in 84 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Alzheimer's Disease Assessment Scale-Cognitive Subscale(ADAS-cog) scores | ADAS-cog will be performed to test the cognition of patients at the enrollment and week 12.The score ranges from 0 to 75，and higher values represent a better outcome. | baseline time,week 12. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Alzheimer's Disease Collaborative research group-Activities of Daily Living(ADCS-ADL)scores | ADCS-ADL will be performed to test the activities of patients at the enrollment,week 6 and week12.The score ranges from 0 to 54，and higher values represent a better outcome. | baseline time,week6,week 12. | 
| Changes of Pittsburgh sleep quality index (PSQI) scores | PSQI will be performed to test the sleep quality of patients at the enrollment ,week 6 and week12.The score ranges from 0 to 21，and higher values represent a worse outcome. | baseline time,week6,week 12. | 
| Changes of Neuropsychiatric Inventory(NPI )scores | NPI will be performed to test the mental symptoms of patients at the enrollment and week12.The score ranges from 0 to 144，and higher values represent a worse outcome. | baseline time,week 12. | 
| Changes of ( Mini-Mental State Examination )MMSE scores | MMSE will be performed to test the cognition of patients at the enrollment and week12.The score ranges from 0 to 30，and higher values represent a better outcome. | baseline time,week 12. | 
| Changes of Montreal Cognitive Assessment (MoCA) scores | MoCA will be performed to test the cognition of patients at the enrollment and week12.The score ranges from 0 to 30，and higher values represent a better outcome. | baseline time,week 12. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer Disease, Brain polypeptide