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

Primary Purpose

Type 2 Diabetes, Diabetic Nephropathy

Status

Unknown status

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

SGLT2 Inhibition

About this trial

This is an interventional treatment trial for Type 2 Diabetes focused on measuring Type 2 diabetes, Diabetic Nephropathy, Albuminuria, SGLT2 inhibitor

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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:
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
Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure..
Pregnant or breastfeeding patients
smoker.

Sites / Locations

Zhongshan Hospital Xiamen UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

No Intervention

Arm Label

normal albuminuria

moderately increased albuminuria

severely increased albuminuria

blank Comparator

Arm Description

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

baseline UACR 30~300 mg/g

baseline UACR>300mg/g

normal participant

Outcomes

Primary Outcome Measures

Change in urinary albuminuria

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 eGFR

eGFR was calculated by modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease.

change in nephrin

To assess effect of SGLT2 inhibition intervention on glomerular podocyte injury by detecting the expression of renal nephrin.

change in TGF-β1

To assess effect of SGLT2 inhibition intervention on glomerular and tubulointerstitial fibrosis by detecting the expression of TGF-β1

change in IL-6

To assess effect of SGLT2 inhibition intervention on inflammation biomarkers by detecting the levels of interleukin-6.

change in TNFα

To evaluate the effects of SGLT2 inhibition treatment on inflammation, biomarkers by detecting the levels of tumor necrosis factor alpha.

changes of AGEs

To evaluate the effects of SGLT2 inhibition treatment on oxidative stress index, the changes of AGEs.

changes of 8-OH-dG

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

Secondary Outcome Measures

Change in uric acid

To evaluate the levels of serum uric acid before and after SGLT2 inhibition treatment.

Change in aldosterone

To evaluate the levels of aldosterone before and after SGLT2 inhibition treatment.

Change in rennin

To evaluate the levels of rennin before and after SGLT2 inhibition treatment

Change in angiotensin

To evaluate the levels of angiotensin before and after SGLT2 inhibition treatment

Full Information

NCT ID

NCT04127084

First Posted

October 8, 2019

Last Updated

October 16, 2019

Sponsor

Zhongshan Hospital Xiamen University

1. Study Identification

Unique Protocol Identification Number

NCT04127084

Brief Title

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

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Unknown status

Study Start Date

October 15, 2019 (Actual)

Primary Completion Date

October 2020 (Anticipated)

Study Completion Date

August 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Zhongshan Hospital Xiamen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes, Diabetic Nephropathy

Keywords

Type 2 diabetes, Diabetic Nephropathy, Albuminuria, SGLT2 inhibitor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

normal albuminuria

Arm Type

Experimental

Arm Description

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

Arm Title

moderately increased albuminuria

Arm Type

Experimental

Arm Description

baseline UACR 30~300 mg/g

Arm Title

severely increased albuminuria

Arm Type

Experimental

Arm Description

baseline UACR>300mg/g

Arm Title

blank Comparator

Arm Type

No Intervention

Arm Description

normal participant

Intervention Type

Drug

Intervention Name(s)

SGLT2 Inhibition

Other Intervention Name(s)

Dapagliflozine,Empagliflozin,Canagliflozin

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in urinary albuminuria

Description

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)

Time Frame

Up to 12 weeks

Title

Change in eGFR

Description

eGFR was calculated by modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease.

Time Frame

Up to 12 weeks

Title

change in nephrin

Description

To assess effect of SGLT2 inhibition intervention on glomerular podocyte injury by detecting the expression of renal nephrin.

Time Frame

Up to 12 weeks

Title

change in TGF-β1

Description

To assess effect of SGLT2 inhibition intervention on glomerular and tubulointerstitial fibrosis by detecting the expression of TGF-β1

Time Frame

Up to 12 weeks

Title

change in IL-6

Description

To assess effect of SGLT2 inhibition intervention on inflammation biomarkers by detecting the levels of interleukin-6.

Time Frame

Up to 12 weeks

Title

change in TNFα

Description

To evaluate the effects of SGLT2 inhibition treatment on inflammation, biomarkers by detecting the levels of tumor necrosis factor alpha.

Time Frame

Up to 12 weeks

Title

changes of AGEs

Description

To evaluate the effects of SGLT2 inhibition treatment on oxidative stress index, the changes of AGEs.

Time Frame

Up to 12 weeks

Title

changes of 8-OH-dG

Description

Time Frame

Up to 12 weeks

Secondary Outcome Measure Information:

Title

Change in uric acid

Description

To evaluate the levels of serum uric acid before and after SGLT2 inhibition treatment.

Time Frame

Up to 12 weeks

Title

Change in aldosterone

Description

To evaluate the levels of aldosterone before and after SGLT2 inhibition treatment.

Time Frame

Up to 12 weeks

Title

Change in rennin

Description

To evaluate the levels of rennin before and after SGLT2 inhibition treatment

Time Frame

Up to 12 weeks

Title

Change in angiotensin

Description

To evaluate the levels of angiotensin before and after SGLT2 inhibition treatment

Time Frame

Up to 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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: 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 Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure.. Pregnant or breastfeeding patients smoker.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Xiao-min Chen, principal

Phone

8613860487599

chenxiaomin0517@sina.com

First Name & Middle Initial & Last Name or Official Title & Degree

Yuan Tian, assistant

Phone

8618250865805

411954353@qq.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yi-lin Zhao, principal

Organizational Affiliation

Zhongshan Hospital Xiamen University

Official's Role

Study Director

Facility Information:

Facility Name

Zhongshan Hospital Xiamen University

City

Xiamen

State/Province

Fujian

ZIP/Postal Code

361004

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yi-lin Zhao, principle

Phone

8613950085931

First Name & Middle Initial & Last Name & Degree

Xiao-min Chen, principle

First Name & Middle Initial & Last Name & Degree

Yuan Tian, assistant

12. IPD Sharing Statement

Citations:

PubMed Identifier

36127497

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.

Results Reference

derived

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

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