Clinical trial NCT05262257: Evaluation and Intervention of Cognitive Function in Patients With Diabetes Mellitus.
Official title: Evaluation and Intervention of Cognitive Function in Patients With Diabetes Mellitus.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Type2 Diabetes
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2022-03-02
Enrollment: 120
Sex: ALL
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized controlled, single-center study of the cognitive function of diabetic patients in the Department of Endocrinology in our hospital. Through the collection of clinical data during the outpatient or hospitalization period, as well as the clinical data of follow-up at different times in the later period, the conclusion is drawn after statistical analysis. For the population who passed the observational study in the first part, patients who meet the conditions of intervention will be further screened to enter the intervention study in the second part. Patients with type 2 diabetes who meet the enrollment criteria and enter the second part are randomly divided into 3 groups according to 1:1:1; 1.Lifestyle intervention group; 2. Metformin treatment group; 3. Dapagliflozin treatment group; There are four groups with healthy control (no intervention). Follow-up review and blood samples were taken after 12 weeks respectively. After the first follow-up, follow-up can be extended to 24 weeks depending on the patient's wishes. Combined with the number of patients with diabetes in endocrinology department of our hospital in the past, and considering the nature of this study and other factors, 90 patients with type 2 diabetes and 30 healthy controls were included for research and analysis.

Detailed description: A large amount of evidence indicates that diabetes (DM) is related to mild cognitive impairment (MCI), vascular dementia and Alzheimer disease (AD). Biological, clinical and epidemiological data all support the close link between diabetes and Alzheimer disease. AD and type 2 diabetes (T2DM) have common pathological features, including inflammation, changes in insulin signaling, or vascular damage. Event-related potential (ERP) is a specific stimulus that acts on the sensory system or a certain part of the brain. When the stimulation is given or withdrawn, the potential change in the brain area is caused. It is suitable for the assessment of brain dysfunction, especially for the assessment of people with early subclinical disease states. Among them, P300 belongs to a kind of ERP, which is an endogenous special evoked potential related to cognitive function. It can identify and evaluate early changes in cognitive function. Therefore, it can be recognized in clinical neurological or psychiatric diseases. The change of cognitive function provides reliable objective indicators, which is of great significance for early drug intervention and treatment and improving the long-term quality of life of patients. Studies have found that anti-diabetic drugs can improve cognitive and memory impairment, and have a positive effect on mitochondrial and synaptic function, neuroinflammation and brain metabolism. Anti-diabetic drugs can be developed as the treatment of MCI and AD diseases in diabetic and non-diabetic patients. Both basic and clinical trials have evidence that metformin has considerable potential for the treatment of cognitive dysfunction in T2DM. Basic experiments have confirmed that SGLT-2 inhibitors may improve the pathological state of AD, but the clinical evidence is still unclear. As the representative drug of SGLT-2, dapagliflozin, as the intervention drug in this study, focuses on its effect on improving the cognitive function of diabetic patients, and compares its effectiveness in improving cognitive function with metformin.

This study is a randomized controlled, single-center study of the cognitive function of diabetic patients in the Department of Endocrinology in our hospital. Through the collection of clinical data during the outpatient or hospitalization period, as well as the clinical data of follow-up at different times in the later period, the conclusion is drawn after statistical analysis. For the population who passed the observational study in the first part, patients who meet the conditions of intervention will be further screened to enter the intervention study in the second part. Patients with type 2 diabetes who meet the enrollment criteria and enter the second part are randomly divided into 3 groups according to 1:1:1;1.Lifestyle intervention group; 2. Metformin treatment group; 3. Dapagliflozin treatment group; There are four groups with healthy control (no intervention). Follow-up review and blood samples were taken after 12 weeks respectively. After the first follow-up, follow-up can be extended to 24 weeks depending on the patient's wishes. Combined with the number of patients with diabetes in endocrinology department of our hospital in the past, and considering the nature of this study and other factors, 90 patients with type 2 diabetes and 30 healthy controls were included for research and analysis.

Eligibility criteria: Inclusion Criteria:

1. some patients with type 2 diabetes were observed and studied:

   * type 2 diabetes was diagnosed according to the 1999 WHO standard and the course of disease was less than 1 year;
   * no hypoglycemic drugs were used or stopped for more than 12 weeks;
   * 40-60 years old (including both ends);
   * able to understand the procedures and methods of this study, willing to strictly abide by the clinical trial plan to complete the trial, and voluntarily signed the informed consent form.
2. healthy controls were age, sex and weight matching:

   * 40-60 years old (including both ends);
   * normal blood glucose: fasting blood glucose\<6.1mmol/l, postprandial 2-hour blood glucose \<7.8mmol /l;
   * able to understand the procedures and methods of this study, willing to strictly abide by the clinical trial plan to complete this trial, and voluntarily signed the informed consent form.

Exclusion Criteria:

* pregnancy or lactation;
* acute complications (including DKA, hypertonic coma) not corrected;
* history of cerebral hemorrhage and stroke;
* other neurological and mental disorders that clearly affect cognitive function, such as anxiety, depression, AD, PD;
* the New York Heart Association (NYHA) defines congestive heart failure as Class III or IV;
* active liver disease and / or obvious abnormal liver function, defined as AST \>2.5 times the normal upper limit and / or ALT\>2.5 times the normal upper limit and / or total bilirubin \> 1.5 times the normal upper limit;
* moderate and severe renal insufficiency \[using CKD-EPI formula to calculate eGFR\<60ml/ (min\*1.73m2)\];
* malignant tumor has not been cured;
* AD family history (first-degree relatives such as parents, siblings, children, etc.). (10) Alcohol or drug abuse within 3 months, which, according to the researchers, may affect the participants' participation in the study or the status of the subjects, resulting in drug use or compliance during the trial (alcohol abuse is defined as alcohol intake of more than 15g a day for women and more than 25g for men (15g alcohol equals 450mL beer, 150mL wine or 50mL low spirits), more than twice a week);
* long-term intravenous administration, oral administration and intra-articular administration of corticosteroids for more than 7 days within 2 months before screening;
* patients with thyroid dysfunction with unstable treatment dose within 3 months (such as thiourea, thyroid hormones);
* severe trauma or infection that may affect blood glucose control within 1 month;
* patients with severe systemic diseases who were judged by the researchers to be unsuitable for enrollment;
* conditions that other researchers considered inappropriate to participate in this clinical trial.

Primary outcomes:
measure: Event-related potential (ERP)
timeFrame: 12 weeks
measure: Montreal Cognitive Assessment(MoCA)
timeFrame: 12 weeks
measure: Mini-Mental State Examination(MMSE)
timeFrame: 12 weeks
Secondary outcomes:
measure: glycated hemoglobin(HbA1c、GHb)
timeFrame: 12 weeks
Other outcomes:
Locations:
Study officials:
References:
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