Type 2 diabetes with early symptomatic dementia
Conditions
Interventions
Placebo-controlled group:Placebo
Mazdutide group:Mazdutide
Sponsors
Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University
Eligibility
Sex/Gender
All
Age
50 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Diagnosed with type 2 diabetes mellitus (T2D) according to the American Diabetes Association criteria; 2.Age between 50 and 75 years old (inclusive), male or female; 3.Early symptomatic dementia (MCI or mild dementia) on the basis of National Institute on Aging–Alzheimer’s Association (NIA-AA) criteria: Mini-Mental State Examination (MMSE) score > 20 and = 0.5; Gradual and progressive memory decline reported by the participant or informant for >= 6 months; 4.Stable glycemic management regimen within 3 months prior to screening, meeting one of the following: Lifestyle intervention (diet and exercise) without any anti-diabetic medications; Oral anti-diabetic medications, with or without once-daily basal insulin; 5.Glycated Hemoglobin (HbA1c) between 7.0% and 9.0% (inclusive); 6.Body Mass Index (BMI) >= 20 kg/m^2, and body weight has remained stable within the past 3 months (change < 5%); 7.Stable cognitive impairment treatment plan within 3 months prior to screening, and able to maintain stability throughout the study, meeting one of the following: No cognitive treatment (neither pharmacological nor non-pharmacological); Non-pharmacological interventions (e.g., cognitive training); Pharmacological treatment (approved symptomatic cognitive enhancers, such as cholinesterase inhibitors or N-methyl-D-aspartate receptor antagonists; disease-modifying therapies for AD are excluded); 8.Able to complete systematic cognitive and functional assessments; 9.Fully understand the study protocol, voluntarily sign the informed consent form, and be willing to comply with the requirements and restrictions outlined in the informed consent and the study protocol throughout the entire study period.
Exclusion criteria
Exclusion criteria: 1.Evidence of the following neurodegenerative diseases: Frontotemporal dementia and its variants; Parkinson’s disease; Dementia with Lewy bodies; Progressive supranuclear palsy; Corticobasal degeneration; Multiple system atrophy; Multiple sclerosis; Huntington’s disease; 2.Current or past history (within the past 2 years) of clinically significant psychiatric disorders, including but not limited to: schizophrenia, bipolar disorder, major depressive disorder, generalized anxiety disorder, and personality disorders; 3.Scores at screening meeting any of the following criteria: (1)Patient Health Questionnaire-9 (PHQ-9) score >= 10; (2)Generalized Anxiety Disorder Scale-7 (GAD-7) score >= 10; 4.History within 3 months prior to screening of: Stroke (ischemic or hemorrhagic); Transient ischemic attack (TIA); Seizures; History of central nervous system (CNS) diseases that may affect cognitive function, including but not limited to CNS infections, intracranial tumors, metabolic encephalopathies, malnutrition-related neurological diseases, and severe traumatic brain injury; 5.History of severe acute complications of diabetes within the past 1 year, such as: diabetic ketoacidosis; hyperosmolar hyperglycemic state, and hypoglycemic coma; 6.Use within 3 months prior to screening of any of the following: GLP-1 RAs; Dual agonists of GLP-1/GIP receptors; Dual agonists of GLP-1/GCG receptors; or GIP/GLP-1/GCG receptor agonists; 7.Use of the following drugs: Regular use of moderate or strong anticholinergic agents (>2 doses/week) within 4 weeks prior to screening; Use within 3 months prior to screening of antiparkinsonian drugs, antiepileptic drugs, antipsychotics, morphine, or anesthetic analgesics (short-term use 21 units for males or >14 units for females (1 unit = 360 ml beer, 150 ml wine, or 45 ml spirits/liquor); 9.History of the following conditions: Medullary thyroid carcinoma; Pancreatitis; Multiple endocrine neoplasia type 2; Gallbladder or biliary tract disease (participants who have had cholecystectomy may be included at the investigator’s discretion); Severe gastrointestinal diseases or history of gastrointestinal surgeries (excluding polypectomy or appendectomy); Malignancy; 10.Uncontrolled or potentially unstable diabetic retinopathy or macular disease; 11.Severe impairment of major organ function, including: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3 times the upper limit of normal; Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m^2 using the CKD-EPI equation; History of unstable angina, myocardial infarction, or heart failure of NYHA Class II or above within 3 months prior to screening; 12.Known or suspected allergy to the investigational product or related products; 13.Women who are pregnant, breastfeeding, planning to become pregnant, or of childbearing potential without using highly effective contraception; 14.Contraindications to MRI scanning, such as implanted metallic prostheses or severe claustrophobia; 15.Participation in other clinical trials within 3 months prior to screening; 16.Any other conditions that the investigator believes may affect the evaluation of efficacy or safety in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Integrated Alzheimer’s Disease Rating Scale; | — |
Secondary
| Measure | Time frame |
|---|---|
| Cognition and Function (Mini-Mental State Examination (MMSE), Clinical Dementia Rating-Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-iADL));Aß plaque deposition measured by Aß-PET/MR imaging;Blood biomarkers of neurodegenerative diseases;Brain structure volume measured by cranial structural magnetic resonance imaging (MRI); | — |
Countries
China
Contacts
Public ContactYan Bi
Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University
Outcome results
None listed