Efficacy and Safety of Wei Li Bai Capsules in the Treatment of Alzheimer's Disease

A Randomized, Double-blind, Placebo-controlled, Multi-center II Clinical Trial to Evaluate the Efficacy and Safety of Wei Li Bai Capsules in the Treatment of Mild to Moderate Alzheimer's Disease

In clinical trials of preclinical pharmacodynamic studies, Wei Li Bai capsules has been proved to significantly improve the learning and memory ability of Alzheimer's disease model. In this study, the researchers will use a multicenter, randomized, double-blind, placebo-controlled parallel method to recruit Alzheimer's disease patients to confirm the efficacy and safety of Wei Li Bai capsules. Confirmation of drug efficacy will be observed through changes in Alzheimer's disease patients' general cognitive function scores, scores of different cognitive domains, daily living activities, and symptom severities.

Wei Li Bai Capsule is composed of sodium ferulate tablets, L-rhamnose and chrysin. Sodium ferulate tablet is a domestically marketed drug, L-rhamnose is a marketed food additive, and chrysin is a dietary supplement. All of them have been widely used and their safety has been confirmed. In addition, since these three compounds all show good potential in the treatment of Alzheimer's disease, and play an important role in regulating metabolism, improving blood circulation and anti-inflammatory and antioxidant, this study will explore the synergistic effect of Wei Libai capsule in patients with mild and moderate Alzheimer's disease in 130 subjects.

Inclusion Criteria:

1. Age 50 to 80 years old (including 50 and 80 years old), male or female;

2. Meet the diagnostic criteria of "likely ad dementia" of the National Institute on aging Alzheimer's disease association (NIA-AA) (2011);

3. The subjects are primary school graduates / graduates and above, and have the ability to complete the cognitive ability test and other tests specified in the program;

4. Memory loss lasted for at least 6 months and tended to worsen gradually;

5. Subjects with mild or moderate illness: 11 ≤ total score of MMSE ≤ 26;

6. Total score of Clinical Dementia Rating Scale (CDR):

   Mild dementia: CDR = 1.0; Moderate dementia: CDR = 2.0;

7. The total score of HIS ≤ 4;

8. The total score of Hamilton Depression Scale (HAMD 17 item version) is ≤ 10;

9. If the subject is currently receiving an approved AD treatment, such as acetylcholinesterase inhibitors (AChEI) and/or memantine, they must have been using a stable dose for at least 4 weeks prior to baseline and maintain a stable dose throughout the study;

10. There was no obvious positive sign in nervous system examination;

11. Coronal scanning of head MRI in screening stage: the MTA grade of medial temporal lobe atrophy visual assessment scale is grade 1-2. If the subject can provide the head MRI film that meets the requirements within 3 month before screening, it can be used as the basis for enrollment without repeated shooting; If the researcher cannot judge whether the subject's condition has changed, the coronal MRI scan of the head before enrollment can be added;

12. The subjects should have stable and reliable caregivers, who will take care of them at least 3 days a week and at least 4 hours a day. The caregivers will accompany the subjects to participate in the whole process of the study. Caregivers must accompany the subjects to the study visit and assist the investigator in completing the Neuropsychiatric Inventory (NPI), Alzheimer's Disease Collaborative Study-Ability of Daily Living Scale (ADCS-ADL), and Clinician Interview Based Impression of Severity (CIBIC -plus), and other scale scores;

13. Agree to participate and sign the informed consent form by the legal guardian. Due to the subject's limited cognitive ability and other reasons, the subject's signature is allowed to be left blank, and the reason is explained. In addition, the legal guardian shall sign the reason statement, and the legal guardian shall sign the informed consent.

Exclusion Criteria:

1. During screening, MRI examination showed significant focal lesions, fulfilling one of the following conditions:

   ① There were more than 2 infarcts with diameter > 2 cm at any site;

   ② MRI examination showed that there were infarcts with arbitrary diameter in key parts (such as thalamus, hippocampus, entorhinal cortex, paraolfactory cortex, angular gyrus, cortex and other subcortical gray matter nuclei);

   ③ Fazekas scale grade of white matter lesions >2;

   ④ There are other imaging evidences that do not support mild and moderate AD.

2. Dementia caused by other reasons: vascular dementia, central nervous system infection, Creutzfeldt Jakob disease, Huntington's disease, Parkinson's disease, Lewy body dementia, traumatic dementia, other physical and chemical factors (such as drug poisoning, alcoholism, carbon monoxide poisoning, etc.), important physical diseases (such as hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial space occupying lesions (such as subdural hematoma, brain tumor), endocrine disorders (such as thyroid disease, parathyroid disease), and vitamin B12, folic acid deficiency or any other known cause;

3. Have suffered from central nervous system diseases (including stroke, optic neuromyelitis, epilepsy, etc.);

4. Subjects who were diagnosed with psychiatric disorders according to DSM-V criteria, including schizophrenia or other mental diseases, bipolar disorder, severe depression or delirium;

5. Abnormal laboratory indexes: liver function (ALT and AST) exceeded 1.5×ULN, renal function (CR) exceeded 1.5×ULN, and creatine kinase exceeded 2×ULN;

6. Untreated hypertensive and hypotensive subjects at screening, or hypertensive subjects with uncontrolled hypertension after treatment; subjects with good blood pressure control after treatment can be determined by the investigator to be suitable for inclusion in this study;

7. Within 1 month of the screening visit, the subject has new or ongoing unstable or serious heart, lung, liver, kidney and hematopoietic diseases according to the judgment of the researcher, and does not meet the conditions for clinical research;

8. Clinically, people with significant allergic reaction history, especially drug allergy history, or known allergy to this product and its excipients;

9. Dyspepsia, esophageal reflux, gastric bleeding or peptic ulcer disease, frequent heartburn (≥ once a week) or any surgical operation that may affect drug absorption (such as partial / total gastrectomy, partial / total small bowel resection and cholecystectomy) within 6 months before screening;

10. Alcohol or drug abusers;

11. Human immunodeficiency virus antibody (ant HIV) and Treponema pallidum antibody (ant TP) are positive;

12. Those who are currently using monoclonal antibody drugs for Alzheimer's disease (e.g., lecanemab, domanemab, etc.), psychotropic drugs, anti-Parkinson drugs, and opioid analgesics within 1 month before the visit;

13. There are uncorrectable visual and auditory disorders, and the neuropsychological test and scale evaluation cannot be completed;

14. Female subjects with positive pregnancy test or lactation and subjects unable to take effective contraceptive measures or have family planning;

15. Participated in other clinical trials within 3 months before the screening visit;

16. There are other situations that the researcher believes are not suitable to participate in this study.