Effects of SGLT2 Inhibition Treatment on Different Levels of Albuminuria in Patients With Type 2 Diabetes: a Prospective Interventional Study
试验速览
- 阶段
- 4 期
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Change in urinary albuminuria
研究概览
简要总结
Diabetic kidney disease has become the leading cause for ESRD worldwide.Albuminuria is a major risk factor for progression of diabetic nephropathy. SGLT2 inhibitors are the first antiglycaemic drugs with direct renoprotection, which are thought to protect the kidneys by lowering albuminuria, stimulating urinary glucose excretion ,reducing systemic blood pressure, while simultaneously improving multiple other risk factors in a glucose-independent manner. However, the precise mechanisms behind the renal beneficial effect of SGLT2 inhibitors are not entirely elucidated, although ongoing outcome trials will confirm these findings. This study is to assess the impact of three months of treatment with SGLT2 Inhibitions on different levels of albuminuria in patients with type 2 diabetes and to evaluate the effects of SGLT2 inhibition treatment on markers for podocyte damage , renal fibrosis, inflammation，oxidative stress and renin-angiotensin- aldosterone system.
详细描述
Objective
The primary objective is to assess the impact of three months of treatment with SGLT2 Inhibition on Different levels of Albuminuria in Patients With type 2 diabetes and to seek the relationship of this influences to relevant risk markers in the pathology of diabetic renal disease.
Design: prospective ，intervention， case-controlled , single center study. Treatment period: 12 weeks. Patient population: 60 patients with type 2 diabetes recruited from Zhongshan Hospital Xiamen University in accordance with the study in- and exclusion criteria.
Intervention: Dapagliflozine 10 mg once daily tablet treatment or Empagliflozin10 mg once daily tablet treatment or Canagliflozin 100 mg once daily tablet treatment. Endpoints: Primary outcome: evaluate the effects of SGLT2 inhibition treatment on on urinary albuminuria, kidney function and eGFR .
Secondary endpoints To assess the effect of SGLT2 inhibition on markers for podocyte damage , renal fibrosis, inflammation，oxidative stress and renin-angiotensin- aldosterone system。 Timeframe: Recruiting planned from October 2019, inclusion over the following 12 months. Last patient is expected to be completed October 2020. Data analysis completed December 2020, publication autumn 2021.
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients between 18 -80 years of age with a diagnosis of type 2 diabetes (WHO criteria).
- •HbA1c of 7-11 %
- •eGFR equal to or above 45 ml/min/1.73 m2
- •The Trial included 20 normal albuminuria (Urinary albumin creatinine ratio [UACR]< 30 mg/g, with 20 moderately increased albuminuria UACR 30~300 mg/g, and 20 severely increased albuminuria UACR>30 0mg/g (in ≥2 out 3 morning spot urine collections prior to enrolment ).at baseline.
- •Patients who agree to receive treatment with SGLT2 inhibitors.
- •Patients must be on current stable hemodynamic profile , without dehydration.
- •Patients must be on current stable antiglycaemic treatment with oral drugs (OAD) or insulin 4 weeks before start of study drug and throughout study duration.
- •Patients must be on stable antihypertensive treatment (not include renin-angiotensin system blocking treatment) 4 weeks before start of study drug and throughout study duration.
排除标准
- •type 1 diabetes
- •Patients who suffer from recent acute complications including diabetic ketoacidosis and hyperglycaemic hyperosmolar coma, which may be at risk for dehydration.
- •Patients with hypertension who are not on stable antihypertensive treatment
- •urinary tract or reproductive tract acute infection
- •impaired liver function, defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
- •History of unstable or rapidly progressing renal disease
- •impaired renal function ,eGFR: <45 mL/min (calculated by MDRD formula)
- •Ongoing cancer treatment
- •Recent Cardiovascular Events in a patient:
- •Acute Coronary Syndrome (ACS) within 2 months prior to enrolment 9.2.Hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment
- •Acute Stroke or TIA within two months prior to enrolment
- •Less than two months post coronary artery revascularization
- •Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure..
- •Pregnant or breastfeeding patients
研究组 & 干预措施
normal albuminuria
baseline urinary albumin creatinine ratio [UACR]< 30 mg/g
干预措施: SGLT2 Inhibition (Drug)
moderately increased albuminuria
baseline UACR 30~300 mg/g
干预措施: SGLT2 Inhibition (Drug)
severely increased albuminuria
baseline UACR>300mg/g
干预措施: SGLT2 Inhibition (Drug)
结局指标
主要结局
Change in urinary albuminuria
时间窗: Up to 12 weeks
a clean-catch 24- hour urine sample and spot urine sample were collected to assess urinary albuminuria,which will be evaluated at week 0, and at end study week 12 (+/- 1 week)
change in nephrin
时间窗: Up to 12 weeks
To assess effect of SGLT2 inhibition intervention on glomerular podocyte injury by detecting the expression of renal nephrin.
Change in eGFR
时间窗: Up to 12 weeks
eGFR was calculated by modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease.
change in TGF-β1
时间窗: Up to 12 weeks
To assess effect of SGLT2 inhibition intervention on glomerular and tubulointerstitial fibrosis by detecting the expression of TGF-β1
change in IL-6
时间窗: Up to 12 weeks
To assess effect of SGLT2 inhibition intervention on inflammation biomarkers by detecting the levels of interleukin-6.
change in TNFα
时间窗: Up to 12 weeks
To evaluate the effects of SGLT2 inhibition treatment on inflammation, biomarkers by detecting the levels of tumor necrosis factor alpha.
changes of AGEs
时间窗: Up to 12 weeks
To evaluate the effects of SGLT2 inhibition treatment on oxidative stress index, the changes of AGEs.
changes of 8-OH-dG
时间窗: Up to 12 weeks
To evaluate the effects of SGLT2 inhibition treatment on oxidative stress index by detecting the levels of 8-OH-dG. Urinary 8-OH-dG concentrations were assayed using a competitive enzyme-linked immunosorbent assay
次要结局
- Change in rennin(Up to 12 weeks)
- Change in angiotensin(Up to 12 weeks)
- Change in uric acid(Up to 12 weeks)
- Change in aldosterone(Up to 12 weeks)