Clinical trial NCT04304261: Effects of SGLT2i on the Cognitive Function in T2DM Patient (ESCDP)
Official title: Effects of Sodium-glucose Co-transporter-2 Inhibitors on the Cognitive Function in Type 2 Diabetic Patient
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Cognitive Functions Confusion
Keywords: Diabetes mellitus
Cognitive Functions
Sodium glucose transporter
Lead sponsor: Third Military Medical University
Sponsor class: OTHER
First posted: 2020-03-11
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Newly onset type 2 diabetes within 3 months
* 7%\<HbA1c\<10%

Exclusion Criteria:

* Type 2 diabetes with acute diabetic complications.
* Type1 diabetes.
* Thyroid dysfuncition.
* Any surgical or medical conditions that significantly influence absorption, distribution, metabolism or excretion of the intervention drugs.
* History of cardio-cerebral vascular events, such as congestive heart failure, myocardial infarction or stroke within 3 months.
* Hepatic insufficiency (AST or AST is twice higher than the upper limit) or history of hepatitis or cirrhosis, hepatic encephalopathy.
* Renal insufficiency (serum creatinine 1.5 times higher than the upper limit) or history of dialysis and nephritic syndrome.
* Acute infections, tumor, severe arrhythmia.
* Alcohol or medicine addiction, psychoactive substance abuse.
* Other diseases affecting cognitive function (congenital dementia, brain trauma, parkinson's diseases, toxicencephacopathy,epilepsy, mental disorders, severe lungdy sfunction, epilepsy, severe hypoglycemic coma, cerebrovascular disease, ischemic heart disease, etc.)
* Fertile woman without contraceptives.
* Allergic to or have contraindication to the intervention drugs.

Primary outcomes:
measure: Changes of cognitive function assessed by cognitive function scale
timeFrame: 12 weeks
Secondary outcomes:
measure: Changes of standardized uptake values of brain and splanchnic organs assessed by 18F-PET-CT
timeFrame: 1 week
measure: Changes of brain function assessed by near infrared brain functional imaging
timeFrame: 4 week
measure: Changes of urinary sodium and glucose excretion (mmol/24h)
timeFrame: 1 week
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Zhiming Zhu
state: Chongqing
Study officials:
References: