NCT02964572已完成不适用
Effect of Sodium Glucose Co-transporter 2 Inhibitor on Inflammatory Cytokine in Type 2 Diabetes
适应症
干预措施
相关药物
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- changes in the secretion of IL-1 beta from peripheral blood mononuclear cells
研究概览
简要总结
- Single-center, prospective, active-controlled, open, randomized, 2 arm parallel, interventional, exploratory pilot
- Type 2 diabetic patients with high cardiovascular risks who have inadequate glycaemic control with metformin-based oral hypoglycemic agents will be prescribed glimepiride (comparison group) or empagliflozin (study group) for 60 days (plus or minus 32 days) as add-on therapy
- Changes in IL-1beta secretion, serum beta-hydroxybutyrate concentration, and NLRP3 inflammasome activity from baseline to final timepoint will be assessed.
详细描述
First among cardiovascular (CV) end point trials of glucose-lowering agents, the EMPA-REG OUTCOME trial-using 10 or 25 mg/day SGLT2 inhibitor empagliflozin against placebo in 7,020 patients with T2DM who were at increased CV risk-reported a 14% reduction in major CV events and marked relative risk reductions in CV mortality (38%), hospitalization for heart failure (35%), and death from any cause (32%) over a median time period of 2.6 years. Though these results have raised the possibility that mechanisms other than those observed in the trial-modest improvement in glycemic control, small decrease in body weight, and persistent reductions in blood pressure and uric acid level-may be at play, it's not clearly known yet.
The inflammatory nature of atherosclerosis is well established. We hypothesized that empagliflozin might have an inhibitory effect on inflammasome activity in macrophages, thus contribute to cardioprotective effects in diabetes.
- Single-center, prospective, active-controlled, open, randomized, 2 arm parallel, interventional, exploratory pilot
- Type 2 diabetic patients with high cardiovascular risks who have inadequate glycaemic control with metformin-based oral hypoglycemic agents will be prescribed glimepiride (comparison group) or empagliflozin (study group) for 60 days (plus or minus 32 days) as add-on therapy
- Changes in IL-1beta secretion, serum beta-hydroxybutyrate concentration, and NLRP3 inflammasome activity from baseline to final timepoint will be assessed
- Healthy volunteers : effect of 3 day-ketogenic diet on changes in cytokines, metabolites (IL-1beta, beta-hydroxybutyrate , etc) and inflammasome activity in macrophages
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥19 years
- •inadequate glycaemic control : HbA1c ≥6.5% or fasting glucose >120 mg/dl or random glucose >180 mg/dl
- •High risk of cardiovascular events defined as the presence of ≥1 of the following:
- •History of myocardial infarction
- •Evidence of multi-vessel coronary artery disease
- •Evidence of single-vessel coronary artery disease with a positive non-invasive stress test for ischemia or history of hospitalization for unstable angina
- •History of stroke
- •Evidence of occlusive peripheral artery disease
- •Evidence of carotid atherosclerosis
- •Metabolic syndrome
- •Healthy volunteers
排除标准
- •Type 1 diabetes
- •Organ transplantation
- •Pregnant women
- •eGFR <45
- •Cortisol or growth hormone deficiency, pituitary diseases
- •Gastric surgery
- •Hematologic disorders
- •Active cancers
研究组 & 干预措施
Glimepiride
Active Comparator
Glimepiride (anti-diabetic drug) as a comparison group
干预措施: Glimepiride (Drug)
Empagliflozin
Experimental
Empagliflozin (anti-diabetic drug) as a study group
干预措施: Empagliflozin (Drug)
结局指标
主要结局
changes in the secretion of IL-1 beta from peripheral blood mononuclear cells
时间窗: Day 60
The effect of empagliflozin on the secretion of IL-1beta from peripheral blood mononuclear cells
次要结局
- Changes in the secretion of TNF-alpha from peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in serum concentrations of beta-hydroxybutyrate, before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in serum concentrations of uric acid (mg/dL), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in serum concentrations of free fatty acid (μEq/L), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in serum concentrations of glucose (mg/dL), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in serum lipids (total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol (mg/dL)), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in spot urine concentrations of glucose (mg/dL) and creatinine (mg/dL) (those will be combined to report spot urine glucose-to-creatinine ratio in mg/mg), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in body weight (kg), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in serum concentrations of insulin (µU/mL), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in serum glycated albumin (%), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in serum concentrations of creatinine (mg/dL), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in mRNA expression level (PCR, fold) of IL-1beta, TNF-alpha, and NLRP3 in peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in serum concentrations of glucagon (pg/mL), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in serum concentrations of liver enzymes (aspartate aminotransferase and alanine aminotransferase (IU/L)), before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
- Changes in protein expression pattern (western blot, relative to control) of IL-1beta, TNF-alpha, and NLRP3 in peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride(Day 60 plus or minus 32 days)
研究者
研究点 (1)
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