Alzheimer's disease
Conditions
Interventions
Control comparator:Donepezil in combination with placebo
experimental group:donepezil in combination with modafinil and paracetamol
Sponsors
The Second Affiliated Hospital of Nanchang University
Eligibility
Sex/Gender
All
Age
65 Years to 85 Years
Inclusion criteria
Inclusion criteria: 1. Patients aged 65 to 85 years who have at least 6 years of education; 2. Patients shall be generally healthy with mobility, reading, vision and hearing sufficient to complete all screening evaluation. 3. Patients and the legal representative must be capable of providing either written informed consent to the study and be willing to comply with study procedures. 4. Patient must meet all of the following clinical criteria for mild to moderate AD dementia according to the National Institute on Aging and Alzheimer's Association (NIA-AA) (2011) criteria, and must comply with the following: (1) History of abnormal memory function > 2 years; (2) No sharp decline in cognitive function or living ability within 6 months prior to screening; (3) Well-controlled other diseases such as brain arterial disease, hypertension (systolic blood pressure 2cm) is no more than 2; (2) No infarct in the key brain area including thalamus, hippocampus, entorhinal cortex, parorhinal cortex, angular gyrus, subcortical gray mass; (3) History or presence of brain atrophy in medial temporal lobe or hippocampus within 6 months prior to screening. 7. Patients must have a stable and reliable caregiver or study partner who can participate in all clinic visitshelp to oversee the patients compliance with the daily treatment and assist in completing the patients clinical assessment at visits, to provide meaningful input into the ADL, NPI and PSQI questionnaires. The caregiver or partner must have a direct contact with patient at least 2 hours per day and 4 days per week. 8. Must be generally in good health (as determined by the Investigator) based on the medical history and screening evaluations.
Exclusion criteria
Exclusion criteria: 1. Patients with family history of AD or dementia. 2. Patients with significant change of symptoms or more than two points of MMSE score from screening to baseline. 3. Patients who are unable to tolerate MRI procedures or contraindication to MRI, including but not limited to cerebral aneurysm clips; implanted nerve stimulators; MRI incompatible pacemakers; implantable cardioverter defibrillators; cochlear implants; implanted infusion pumps; other magnetic, electronic, or mechanical implants; or any other clinical history or examination finding that in the opinion of the investigator would pose a potential hazard in combination with MRI. 4. Suspected or known drug or alcohol abuse within 5 years prior to screening. Alcohol abuse is defined by quantity of daily alcohol use (male >=40g alcohol, female >= 20g or heavy drinking history within 2 weeks). 5. Patients who have any of the following situationhistory of contraindications or may require a long-term continuous use of contraindications during the research: (1) A history of hypersensitivity or allergic reaction to any of the experimental agents; (2) A continuous requirement of monamine inhibitors, erotonin uptake inhibitors or dopamine uptake inhibitors within 3 months prior to the screening or anytime during the research. (3) A continuous requirement for any central medicine of sedation antianxietyanti-depressionanti-psychiatric diseases and anti-Choline within 2 months prior to the screening or anytime during the research which may have an interact with experimental drug or affect clinical evaluation of treatment. (4) CYP3A4 inhibitors or contraindications used 7 day prior to the screening, or a continuous requirement for any of them during the research. (5) Possibility for taking extra acetaminophen or other drugs containing APAP more than 1.2g per day during the research; (6) Taking any medicine or health product to improve cerebral function at the screening and having the potential for continued use during the study (7) Possibility for taking any other medicine for AD treatment 6. Patients who have a prior history or evidence of unstable or clinically significant disease that in the investigators opinion may interfere with outcome evaluationssuch as (1) Other primary causes of dementia: VaD or Lewy body dementiacentral nervous system infectionParkinsons diseasehead trauma, intracranial space-occupying lesions, endocrine system disease (i.e. abnormal thyroid function, vitamin B12 deficiency, folic acid, or any other known causes of dementia). (2) Cerebrovascular condition contributed to the participant's cognitive impairment such as significant stenosis of carotid artery or vertebral artery, aortic aneurysm, intracranial aneurysm, cerebral hemorrhage, arteriovenous malformationor transient ischemic attack or stroke within 3 years prior to screening (3) Systemic autoimmune diseases which might affect the evaluation including but not limitedlupus erythematodes, antiphospholipid antibody syndrome, Behcet disease. (4) History of gastrointestinal diseases affecting absorption, distribution, metabolism, for example intestinal inflammationgastric or duodenal ulcerc or severe lactose intoleranceetc. (5) History of significant unstable psychiatric illness according to the DSM-V criteria (e.g., uncontrolled major depression, uncontrolled schizophrenia, uncontrolled bipolar affective disorder). (6) Major risk factors for malignant melanoma such as angioderma pigmentosum,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| the change of ADAS-Cog from baseline to week 24 after the treatment in patients with mild and moderate AD and the difference between the experimental group and control group; | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes of MMSE and CSI in different periods of treatment compared to the baseline;Percentage of patients with Treatment-Emergent Adverse Events (TEAEs) in SS analysis set;3. Plasma Pharmacokinetics (PK): Maximum and minimum observed value of steady plasma-drug concentration; | — |
Countries
China
Contacts
Public ContactZhenyu Tang
The Second Affiliated Hospital of Nanchang University
Outcome results
None listed