Alzheimers disease
Conditions
Interventions
low dose:low dose JWK003
Sponsors
West China Hosiptal of Sichuan University
Eligibility
Sex/Gender
All
Age
50 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Men and women over 50 years old during the screening visit; 2. Patients with mild AD who meet the diagnostic criteria proposed by the National Institute on Aging and Alzheimer's Association (NIA-AA) in 2018 and have a disease duration of more than 6 months: (1) Have evidence of Aß deposition biomarkers (abnormal amyloid protein deposition on PET or low cerebrospinal fluid Aß42 or Aß42/Aß40 ratio) and tau biomarkers (CSF or PET); (2) Have Alzheimer's clinical syndrome: having cognitive impairment in one or more cognitive domains, which can be a typical change dominated by memory impairment or a variant type of cognitive dysfunction syndrome; (3) Have neurobehavioral symptoms: presenting symptoms of emotional or behavioral disorders, such as anxiety, depression, and apathy; 3. Have the APOE genotype of APOE E3/E3, E3/E4, or E4/E4; 4. During the screening, the Clinical Dementia Rating Scale (CDR-GS) score is between 0.5 and 1; 5. Within 12 months before randomization, the Mini-Mental State Examination score is between 11 and 26 (11 <= university <=26, 11 <= middle school <= 24, 11 <= primary school <= 23), and the brain CT or MRI performed during the screening visit is consistent with the suspected diagnosis of Alzheimer's disease; 6. The physical examination, laboratory data, and electrocardiogram results of the screening visit must be normal or abnormal findings must be judged to have no clinical significance; 7. The score on the Hamilton Depression Scale is <= 12, and there is no history of severe depression in the past 2 years; 8. There are no obvious neurological or medical abnormalities that prohibit surgery, MRI/PET imaging, or participation in the study; 9. Can walk, and at least need to rely on assistive devices; 10. Vision and hearing are sufficient to meet the test requirements; 11. The informed consent form must be signed by the following two parties: the capable and voluntary participant, and the agent determined by the participant, or a legal medical authorization form, or a family member; 12. Can follow the requirements of this study, including relevant clinical examinations, etc.
Exclusion criteria
Exclusion criteria: 1. There are cognitive impairments caused by frontal-temporal lobe degeneration, vascular dementia (except for mild vascular cognitive impairment related to risk factors), normal pressure hydrocephalus, and other diseases (such as brain trauma or surgery, infection, immunity, tumor, poisoning and metabolic diseases, etc.); 2. There is severe dysfunction of important organs (heart, lungs, liver, kidneys, etc.): such as severe cardiovascular diseases (hospitalization due to myocardial infarction or heart surgery within 3 months, congestive heart failure or myocardial infarction, severe unstable arrhythmia, hypertrophic cardiomyopathy, severe aortic stenosis, aneurysm, etc.), severe pulmonary diseases (severe pneumonia, respiratory failure, etc.), liver dysfunction (alanine aminotransferase more than three times the upper limit of normal), kidney dysfunction (creatinine, urea nitrogen more than 1.5 times the upper limit of normal), total bilirubin and/or direct bilirubin > 1.5 mg/dL, hemoglobin < 9 mg/dL, HBV or HCV serology positive; absolute neutrophil count < 1,500 cells/mm^3 and platelet count < 100,000/mm^3, etc., as determined by the investigator, are not suitable to participate in this clinical trial; 3. Have or previously had Parkinson's disease or mental disorders, such as schizophrenia, bipolar disorder, severe depression or anxiety, etc.; 4. CT or MRI evidence of hydrocephalus, stroke, space-occupying lesion, brain infection or any other clinically significant central nervous system diseases; 5. Within the past year or currently using drugs targeting Aß amyloid protein deposition, such as Leqembi, etc.; 6. Patients with hematological malignancies or solid tumors who are undergoing treatment, have completed treatment within the past 6 months or still have evidence of active disease; 7. Current drug or alcohol dependence, including nicotine addiction (smokers); 8. Subjects receiving immunosuppressants, tricyclic antidepressants, anticoagulants or chemotherapy drugs; 9. Have acute sinusitis, acute rhinitis, or chronic sinusitis, chronic rhinitis with acute attack symptoms, etc. in the subjects; 10. Abnormal conditions in the nasal cavity that may affect drug administration as judged by the clinical doctor, such as nasal granuloma, nasal septum deviation, nasal polyps, etc.; 11. Received any nasal drug treatment or nasal surgery before the treatment; 12. Poorly controlled or managed hypertension; 13. Had clinically significant systemic diseases or severe infections within 30 days before screening or during screening; 14. Used dose-unstable chronic disease drugs for at least 4 weeks before the first screening visit, or used dose-unstable AD drugs for at least 8 weeks before the first screening visit; 15. Subjects who participated in other clinical trials within 3 months before enrollment in this trial, or are currently participating in other clinical trials, have a history of any kind of gene transfer product; 16. Use any drugs that the investigator believes may cause cognitive impairment, expose the participants to a higher risk of adverse events (AE), or impair the participants' ability to perform cognitive tests or complete the research procedures; 17. Exclusion criteria of the research procedure.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Score of the cognitive part of the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical Dementia Rating (CDR) score ;The scores of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA);Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder Scale - 7 items (GAD-7), and Patient Health Questionnaire - 9 items (PHQ-9) scores;Neuro-Psychiatric Inventory (NPI) score;Digital Span Test (DST), Trail Making Test - Block Design (TMT-B), Clock Drawing Test Score;Changes in PET-MRI, MRI, and sleep electroencephalogram;Concentrations of plasma Aß oligomers, Aß40 and Aß42, as well as the ratio of Aß42 to Aß40, changes compared to baseline;The changes in PF4 levels in blood and cerebrospinal fluid compared to the baseline; | — |
Countries
China
Contacts
Public ContactLei Chen/Xiawei Wei
West China Hospital of Sichuan University
Outcome results
None listed