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

NCT ID: NCT04127084

Last Updated: 2019-10-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-15
• Study Completion Date: 2021-08-31

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.

Conditions

Type 2 Diabetes; Diabetic Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

normal albuminuria

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

Group Type: EXPERIMENTAL

SGLT2 Inhibition

Intervention Type: DRUG

Dapagliflozine 5-10 mg once daily tablet treatment or Empagliflozin10 mg once daily tablet treatment or Canagliflozin 100 mg once daily tablet treatment

moderately increased albuminuria

baseline UACR 30\~300 mg/g

Group Type: EXPERIMENTAL

SGLT2 Inhibition

Intervention Type: DRUG

Dapagliflozine 5-10 mg once daily tablet treatment or Empagliflozin10 mg once daily tablet treatment or Canagliflozin 100 mg once daily tablet treatment

severely increased albuminuria

baseline UACR\>300mg/g

Group Type: EXPERIMENTAL

SGLT2 Inhibition

Intervention Type: DRUG

Dapagliflozine 5-10 mg once daily tablet treatment or Empagliflozin10 mg once daily tablet treatment or Canagliflozin 100 mg once daily tablet treatment

blank Comparator

normal participant

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

SGLT2 Inhibition

Dapagliflozine 5-10 mg once daily tablet treatment or Empagliflozin10 mg once daily tablet treatment or Canagliflozin 100 mg once daily tablet treatment

Intervention Type: DRUG

Other Intervention Names

Dapagliflozine,Empagliflozin,Canagliflozin

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhongshan Hospital Xiamen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yi-lin Zhao, principal

Role: STUDY_DIRECTOR

Zhongshan Hospital Xiamen University

Locations

Zhongshan Hospital Xiamen University

Xiamen, Fujian, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiao-min Chen, principal

Role: CONTACT

chenxiaomin0517@sina.com

8613860487599

Yuan Tian, assistant

Role: CONTACT

411954353@qq.com

8618250865805

Facility Contacts

Yi-lin Zhao, principle

Role: primary

8613950085931

References

Zeng XC, Tian Y, Liang XM, Wu XB, Yao CM, Chen XM. SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway. Diabetol Metab Syndr. 2024 Feb 16;16(1):46. doi: 10.1186/s13098-024-01280-5.

Reference Type: DERIVED

PMID: 38365853 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36127497 (View on PubMed)

Other Identifiers

20191005

Identifier Type: -

Identifier Source: org_study_id