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Type 2 diabetes is associated with diabetic cognopathy, the prevalence of Alzheimer's Disease(AD) in T2DM patients is 1.5 to 2.5 times higher than the general population. Cognitive impairment seriously affects the health and quality of life of the elderly. Prevention and treatment measures for cognitive decline in persons with T2DM has not been well studied.
Sodium-glucose transporter-2 (SGLT-2) inhibitors, which lower serum glucose by inhibiting SGLT2-mediated glucose reabsorption in renal proximal tubules, could be neuroprotective. It was recently reported that the SGLT-2 inhibitor improved cognitive function and ameliorated oxidative stress via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in mice or HFD-induced obese rats, that means SGLT-2 inhibitor may provide neuroprotection in the diabetic brain. Hence, Invokana (Canagliflozin) might act as a potent dual inhibitor of AChE and SGLT2. Since the development of diabetes is associated with AD, the design of new AChE inhibitors based on antidiabetic drug scaffolds would be particularly beneficial. Moreover, the present computational study reveals that Invokana (Canagliflozin) is expected to form the basis of a future dual therapy against diabetes associated neurological disorders.
The overall goal of this study is to explore the effects of SGLT2 inhibitor on the cognitive function in patients with type 2 diabetes mellitus and make further contribution to the improvement of cognitive function.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Canagliflozin | Experimental | 12 weeks of Canagliflozin(100mg/day) treatment, randomly |
|
| Sitagliptin | Experimental | 12 weeks of Sitagliptin (100mg/day) treatment, randomly |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Canagliflozin | Drug | 12 weeks of Canagliflozin(100mg/day) treatment |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Changes of cognitive function assessed by cognitive function scale | cognitive function scale | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Changes of standardized uptake values of brain and splanchnic organs assessed by 18F-PET-CT | 18F-PET-CT | 1 week |
| Changes of brain function assessed by near infrared brain functional imaging | near infrared brain functional imaging |
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Inclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zhiming Zhu | Chongqing | Chongqing Municipality | 400042 | China |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003221 | Confusion |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000068896 | Canagliflozin |
| D000068900 | Sitagliptin Phosphate |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D006573 | Heterocyclic Compounds, 1-Ring |
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| Sitagliptin |
| Drug |
12 weeks of Sitagliptin (100mg/day) treatment |
|
| 4 week |
| Changes of urinary sodium and glucose excretion (mmol/24h) | urinary sodium and glucose excretion | 1 week |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006571 |
| Heterocyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D014230 | Triazoles |
| D001393 | Azoles |
| D011719 | Pyrazines |