Clinical trial NCT04127084: Effects of SGLT2 Inhibition Treatment on Different Levels of Albuminuria in Patients With Type 2 Diabetes
Official title: Effects of SGLT2 Inhibition Treatment on Different Levels of Albuminuria in Patients With Type 2 Diabetes: a Prospective Interventional Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Type 2 Diabetes
Diabetic Nephropathy
Keywords: Type 2 diabetes
Diabetic Nephropathy
Albuminuria
SGLT2 inhibitor
Lead sponsor: Zhongshan Hospital Xiamen University
Sponsor class: OTHER
First posted: 2019-10-15
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients between 18 -80 years of age with a diagnosis of type 2 diabetes (WHO criteria).
2. HbA1c of 7-11 %
3. eGFR equal to or above 45 ml/min/1.73 m2
4. 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.
5. Patients who agree to receive treatment with SGLT2 inhibitors.
6. Patients must be on current stable hemodynamic profile , without dehydration.
7. 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.
8. 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.

Exclusion Criteria:

1. type 1 diabetes
2. Patients who suffer from recent acute complications including diabetic ketoacidosis and hyperglycaemic hyperosmolar coma, which may be at risk for dehydration.
3. Patients with hypertension who are not on stable antihypertensive treatment
4. urinary tract or reproductive tract acute infection
5. impaired liver function, defined as aspartate aminotransferase (AST) \>3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) \>3x ULN
6. History of unstable or rapidly progressing renal disease
7. impaired renal function ,eGFR: \<45 mL/min (calculated by MDRD formula)
8. Ongoing cancer treatment
9. Recent Cardiovascular Events in a patient:

   9.1. 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 enrolment9. 3. Acute Stroke or TIA within two months prior to enrolment 9. 4. Less than two months post coronary artery revascularization
10. Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure..
11. Pregnant or breastfeeding patients
12. smoker.

Primary outcomes:
measure: Change in urinary albuminuria
timeFrame: Up to 12 weeks
measure: Change in eGFR
timeFrame: Up to 12 weeks
measure: change in nephrin
timeFrame: Up to 12 weeks
measure: change in TGF-β1
timeFrame: Up to 12 weeks
measure: change in IL-6
timeFrame: Up to 12 weeks
measure: change in TNFα
timeFrame: Up to 12 weeks
measure: changes of AGEs
timeFrame: Up to 12 weeks
measure: changes of 8-OH-dG
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Change in uric acid
timeFrame: Up to 12 weeks
measure: Change in aldosterone
timeFrame: Up to 12 weeks
measure: Change in rennin
timeFrame: Up to 12 weeks
measure: Change in angiotensin
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Xiamen
country: China
facility: Zhongshan Hospital Xiamen University
state: Fujian
Study officials:
affiliation: Zhongshan Hospital Xiamen University
name: Yi-lin Zhao, principal
role: STUDY_DIRECTOR
References:
citation: Tian Y, Chen XM, Liang XM, Wu XB, Yao CM. SGLT2 inhibitors attenuate nephrin loss and enhance TGF-beta1 secretion in type 2 diabetes patients with albuminuria: a randomized clinical trial. Sci Rep. 2022 Sep 20;12(1):15695. doi: 10.1038/s41598-022-19988-7.