Effects of SGLT2 Inhibition Treatment on Different Levels of Albuminuria in Patients With Type 2 Diabetes

Xiamen University

Status and phase: Unknown; Phase 4

Conditions: Diabetic Nephropathy; Type 2 Diabetes

Treatments: Drug: SGLT2 Inhibition

Study type: Interventional

Funder types: Other

Identifiers

NCT04127084

20191005

Details and patient eligibility

About

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.

Full 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.

Enrollment: 70 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 4 patient groups

normal albuminuria

Experimental group

Description:

baseline urinary albumin creatinine ratio \[UACR\]\< 30 mg/g

Treatment:

Drug: SGLT2 Inhibition

moderately increased albuminuria

Experimental group

Description:

baseline UACR 30\~300 mg/g

Treatment:

Drug: SGLT2 Inhibition

severely increased albuminuria

Experimental group

Description:

baseline UACR\>300mg/g

Treatment:

Drug: SGLT2 Inhibition

blank Comparator

No Intervention group

Description:

normal participant