Efficacy and Safety of 1612 Capsules in aMnestic Mild Cognitive Impairment

Study Overview
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Brief Summary
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This study is a 52-weeks, multicenter, randomized, double-blind, placebo controlled, parallel trial which will be carried out in 15 centers around China. The study population includes amnestic mild cognitive impairment patients (planned a total of 240) aged 55-85 in both gender. Participants will be randomly allocated to 1612 capsules (1.14g per time, 3 times per day) or placebo for a 52-weeks double-blind treatment period. The primary outcome measure is change from baseline in the Alzheimer's Disease Assessment Scale- Cognition Subscale (ADAS-cog) and rate of conversion to dementia. The secondary outcomes are changes from baseline in the Mini-Mental State Examination (MMSE), Delayed Story Recall test (DSR), Alzheimer's Disease Cooperative Study/Activities of Daily Living scale adapted for MCI patients (ADCS/MCI/ADL24). Safety is being assessed by observing side effects and adverse reaction during the entire treatment period. Statistical analysis will be conducted according to per-protocol population and intend-to-treat population and the safety will be analyzed in safety set.

Official Title
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The Safety and Efficacy of 1612 Capsules in Treatment of aMnestic Mild Cognitive Impairment: a 52-week, Double Blind,Randomized, Parallel,Placebo Controlled Trial.

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Drug: 1612 capsule
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients should be enrolled if they met the following criteria[14]: cognitive complaints from the patients or their families; objective evidence for memory impairment, delayed story recall test(DSR)<12.6(age50-64 less than15.5,65-74less than 12.5,older 75 less than10); normal general cognitive function, with Mini-Mental State Examination (MMSE) score of between 24 and 30 (including 30); preservation of activities of daily living, with Alzheimer's Disease Cooperative Study/Activities of Daily Living scale adapted for MCI patients (ADCS/MCI/ADL24) score between 38 and 52; cognitive disorders as evidenced by clinical evaluation, with clinical dementia rating scale=0.5,memory domain = 0.5; absence of dementia, not sufficiently impaired cognitively and functionally to meet DSM-IV criteria, enough vision and hearing to accomplishment neuropsychological test; capability to read words and write simple sentence; capability and willingness to give informed consent and to comply with the study procedures. Exclusion Criteria: The patients would be ineligible if they had the following conditions: non amnestic Mild cognitive impairment; meeting the diagnostic criteria for dementia; cognitive impairment resulting from conditions such as acute cerebral trauma, cerebral damage due to a lack of oxygen, epilepsy vitamin deficiency, infections such as meningitis or AIDS, significant endocrine or metabolic disease, mental retardation, or a brain tumor ,or drug abuse or alcohol abuse having significant psychiatric disease, depression, the Hamilton depression scale >12; CT or MRI scan showed central nervous system infections Infarction or focal lesions within 12 months，the Hachinski Ischemic Scale (HIS)>4; combined following disease: diabetes; poor controlled hypertension or severe arrhythmias; or suffered from heart infarction within 3 months; severe asthma or COPD; severe indigestion; gastrointestinal tract obstruction; gastroduodenal ulcer; used cholinesterase inhibitors or memantine within 1 month; history of hypersensitivity to the treatment drugs; concomitant drugs with the potential to interfere with cognition; administration of other investigational drugs; severe impairment of the functions of the kidney or liver; vegetarians or contraindications for animal innards.

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 |
| --- | --- |
| Experimental: 1612 capsule<br>Subjects will take 1612 capsule 3 capsules per time(0.38g per capsule), 3 times per day for 52 weeks | Drug: 1612 capsule<br>* Subjects will be assigned 1612 capsule,3 capsules per time(0.38g per capsule), 3 times per day.1612 capsule is a Chinse herbal medicine,which can tonification of spleen and kidney, mainly contains shudihuang(Rehmannia glutinosa),shanyao(Dioscorea opposita),shichangpu(Uncaria rhynchophylla)and so on,<br>|
| Placebo Comparator: Placebos<br>Subjects will take palcebo identified to 1612 capsule 3 capsules per time, 3 times per day for 52 weeks | Drug: Placebos<br>* Subjects will be assigned placebo identified to 1612 capsule,3 capsules per time, 3 times per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive scores: Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) | Cognition will accessed with the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), at baseline (day 1 clinic visit) and week 4, week 12, week 24 ,week 36 , week 48 and week 52. | 52 weeks | 
| Change from baseline to end of double-blind treatment of rate of dementia conversion from mild cognitive impairment | The rate of demention conversion will accessed from baselin at week 0 and week 4, week 12, week 24 ,week 36 , week 48 and week 52. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to end of double-blind treatment of Mini-Mental State Examination(MMSE) | Cognition will accessed with the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), at baseline (day 1 clinic visit) and week 4, week 12, week 24 ,week 36 , week 48 and week 52. | 52 weeks | 
| Change from baseline to end of double-blind treatment of Delayed Story Recall test (DSR) | Memory will accessed with the delayed story recall test(DSR), at baseline (day 1 clinic visit) and week 4, week 12, week 24 ,week 36 , week 48 and week 52. | 52 weeks | 
| Change from baseline to end of double-blind treatment of Alzheimer's Disease Cooperative Study/Activities of Daily Living scale adapted for MCI patients (ADCS/MCI/ADL24) | Ability of daily living will accessed with the Alzheimer's Disease Cooperative Study/Activities of Daily Living scale adapted for MCI patients (ADCS/MCI/ADL24), at baseline (day 1 clinic visit) and week 4, week 12, week 24 ,week 36 , week 48 and week 52. | 52 weeks |