Efficacy and Safety of Donepezil and Sodium Oligomannate in Patients With Mild to Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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Alzheimer's disease (AD) is the main cause of dementia. At present, AD is incurable. Cholinesterase inhibitors, especially donepezil, are the first choice for mild and moderate AD. Sodium oligomannate (GV-971) is a marine-derived oligosaccharide. It is proposed that it can reconstitute the gut microbiota, and inhibit neuroinflammation in the brain as observed in animal models. It reduces Aβ deposition in the brain of Aβ-transgenic mice. The reduction in both Aβ deposition and neuroinflammation may synergistically contribute to the improvement of cognitive impairment and delay the progress of the disease. The State Food and Drug Administration of China (SFDA) approved it for the treatment of mild to moderate AD in 2019. Due to the different mechanism of cholinesterase inhibitor and GV-971, theoretically, they may synergistically improve cognitive function and delay disease progression. They are also used in patients with AD, but there is a lack of data on their effectiveness and safety. Therefore, the purpose of this observational study is to compare the efficacy and safety of donepezil and GV-971 monotherapy and combination therapy in patients with mild and moderate AD, which is of great significance for guiding the treatment of mild and moderate AD.

Official Title
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Efficacy and Safety of Donepezil and Sodium Oligomannate in Patients With Mild to Moderate Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Donepezil
* Drug: GV-971


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age of 50-85 years old , either sex; met the diagnostic criteria for suspected AD; mild to moderate AD patients, that is, patients with 11 points ≤Mini-Mental State Examination(MMSE) total score ≤26 points total Hachinski ischemic scale (HIS) score ≤4 points; memory loss for at least 12 months, with a tendency of progressive deterioration; brain magnetic resonance imaging（MRI） scan suggesting a significant possibility of AD ; no obvious physical signs during nervous system examination; stable and reliable caregivers, elementary school or higher education level signed an informed consent form Exclusion Criteria: previous nervous system diseases (including stroke, optic neuromyelitis, Parkinson's disease, epilepsy, etc.); mental illness according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition（DSM-IV), Text Revision criteria, including schizophrenia and other mental illness, bipolar disorder, and severe depression or paralysis; unstable or severe heart, lung, liver, kidney, or hematopoietic diseases; uncorrectable visual and auditory disorders that affected completing neuropsychological tests and scale assessments; simultaneous use of cholinesterase inhibitors or memantine.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Donepezil monotherapy group<br>Donepezil 5mg qd | Drug: Donepezil<br>* Donepezil 5mg qd<br>|
| GV-971 monotherapy group<br>GV-971 450mg bid | Drug: GV-971<br>* GV-971 450mg bid<br>|
| Donepezil combined with GV-971 group<br>Donepezil 5mg qd+GV-971 450mg bid | Drug: Donepezil<br>* Donepezil 5mg qd<br>Drug: GV-971<br>* GV-971 450mg bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cognitive function | the change of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) score from baseline at week 36 | baseline, week 12, week 24, week 36 |