Guilingji Capsule for Mild-to-moderate Cognitive Impairment

Study Overview
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Brief Summary
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This study is aiming to evaluate the efficacy and safety of Guilingji capsule in older adults with mild-to-moderate cognitive impairment who diagnosed as the kidney and marrow deficiency pattern in TCM. A total of 348 participants are evenly assigned to two arms. In the intervention arm, participants receive Guilingji capsule and Ginko Biloba Extract mimetic in combination, while the other arm will receive Ginko Biloba Extract tablet with Gulingji mimetic.

Detailed Description
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This study is a multi-center, randomized, positive control, noninferiority clinical trials. Experimental arm (174 cases) take 0.6 g of Gulingji capsules once a day and 19.2 mg of Ginko Biloba Extract mimetic three times a day. Active Comparator arm (174 cases) should take 0.6 g of Gulingji mimetic once a day and 19.2 mg of Ginko Biloba Extract tablet three times a day. The intervention lasted for 24 weeks. Clinical researchers, participants and statisticians are blinded to the treatment assignment throughout the study. Co-primary efficacy endpoints are change from baseline to week 12 and 24 in Mini-Mental State Examination score and Montreal Cognitive Assessment (MoCA) total score.Change from baseline to week 12 and 24 in Clinical Dementia Rating score, Alzheimer's Disease Assessment Scale-Cognitive subscale score, Activities of Daily Living, and Chinese Medicine Symptom Scale scoreare additional endpoints. Prespecified secondary biomarker endpoint is change from baseline in the serum level of acetylcholine and acetylcholinesterase at week 24.

Official Title
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Efficacy and Safety of Guilingji Capsule in Older Adults With Mild-to-Moderate Cognitive Impairment (Kidney and Marrow Deficiency Pattern)

Conditions
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Cognitive Dysfunction

Intervention / Treatment
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* Drug: Gulingji capsules
* Drug: Ginko Biloba Extract tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 60 and 85 years old With a disease course ≥ 6 months and confirmed by others Mini-Mental State Examination (MMSE) score between 10 and 26, or MMSE score >26 but Montreal Cognitive Assessment (MoCA) score<26 Meeting the diagnostic criteria of mild-to-moderate cognitive impairment Meeting the diagnostic criteria of kidney deficiency pattern in Traditional Chinese medicine Screening visit brain MRI and CT scan consistent with the diagnosis of mild-to-moderate cognitive impairment Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments Received a primary and/or a higher education Lives at home with appropriate caregiver capable of accompanying the subject on all clinic visits, or community dwelling with caregiver capable of accompanying the subject on all clinic visits and visiting with the subject approximately 5 times per week for the duration of the study Signed and dated written informed consent. The subject's caregiver must also consent to participate in the study Exclusion Criteria: Significant neurological disease, other than AD MCI and VaD, that may affect cognition, such as the Parkinson's disease, the Huntington's disease, normal pressure hydrocephalus, brain tumors, progressive supra-nuclear palsy, epilepsy, chronic subdural hematoma and multiple sclerosis, history of severe head trauma with persistent neurological deficits or known abnormal brain structure Thyroid disease, vitamin B12 or folic acid deficiency, severe anemia or malnutrition, serious heart, liver, lung, kidney and other organ diseases that may affect the cognitive function Allergic to Ginkgo products Use of any other medications with the potential to affect cognition Current presence of a clinically important major psychiatric disorder or symptom Alcohol addiction, or long-term use of antipsychotic drugs, or a history of severe head trauma Cannot complete with cognitive function examines.

Ages Eligible for Study
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Minimum Age: 60 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>In this arm, patients take 0.6g of Gulingji capsules, 2 hours before breakfast, served with light salt water once a day. Also an oral take of 19.2mg Ginko Biloba Extract mimetic three times a day. Treatment lasts for 24 weeks. | Drug: Gulingji capsules<br>* Patients take 0.6g of Gulingji capsules, 2 hours before breakfast, served with light salt water once a day. Also an oral take of 19.2mg Ginko Biloba Extract mimetic three times a day. Treatment lasts for 24 weeks.<br>|
| Active Comparator: Control<br>In this arm, patients take 0.6g of Gulingji mimetic, 2 hours before breakfast, served with light salt water once a day. Also an oral take of 19.2mg Ginko Biloba Extract tablet three times a day. Treatment lasts for 24 weeks. | Drug: Ginko Biloba Extract tablet<br>* Patients take 0.6g of Gulingji mimetic, 2 hours before breakfast, served with light salt water once a day. Also an oral take of 19.2mg Ginko Biloba Extract tablet three times a day. Treatment lasts for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change From Baseline in Mini-Mental State Examination (MMSE) Total Score at Week 12 and 24 | MMSE is a 30-point questionnaire and contains items assessing orientation, memory, attention and calculation, naming and visuospatial skills of patients. | Baseline,12th week±3 days, 24th week±3 days | 
| The Change From Baseline in Montreal Cognitive Assessment (MoCA) Total Score at Week 12 and 24 | MoCA is a 30-point questionnaire and evaluates orientation, executive function, language ability, short-term memory, attention and visuospatial ability. | Baseline,12th week±3 days, 24th week±3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change From Baseline in Clinical Dementia Rating (CDR) Total Score at Week 12 and 24 | The CDR test is a numeric scale used to quantify the severity of symptoms of dementia. It sums 6 clinical ratings: 1) memory, 2) orientation, 3) judgment and problem solving, 4) involvement in community affairs, 5) home and hobbies, and 6) personal care based on the CDR interview. The CDR includes discussions with the participant and caregiver using a structured format. CDR total score range is 0 (least impairment) to 18 (most impairment); a negative change from baseline indicates an improvement. | Baseline,12th week±3 days, 24th week±3 days | 
| The Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Total Score at Week 12 and 24 | The ADAS-Cog is a multi-item, objective measure of cognitive function. Analysis of the ADAS-Cog for this study is based upon an 12 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4) constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8) remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, 11) comprehension, and 12) attention during the test. The ADAS-Cog ranged from 0 to 75 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment. | Baseline,12th week±3 days, 24th week±3 days | 
| The Change From Baseline in Activities of Daily Living (ADL) Total Score at Week 12 and 24 | The ADL is a test used in healthcare to evaluate the people's daily self care activities. | Baseline,12th week±3 days, 24th week±3 days | 
| The Change From Baseline in The Chinese Medicine Symptom Scale (CM-SS) Total Score at Week 12 and 24 | The CM-SS is a tool, designed according to the Guiding Principles of Clinical Research on New Drugs of Traditional Chinese Medicine issued in 2002, to evaluate the effects of treatments on Traditional Chinese medicine patterns (here refers to kidney deficiency pattern). Scoring is mainly based on some typical TCM symptoms, such as tongue coating and pulse. | Baseline,12th week±3 days, 24th week±3 days | 
| The Change From Baseline in The Serum Level of Acetylcholine and Acetylcholinesterase at Week 24 | Acetylcholine and acetylcholinesterase are potential circulatory biomarkers of cognitive dysfunction. | Baseline, 24th week±3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traditional Chinese medicine, Randomized clinical trial, Mild-to-moderate cognitive impairment