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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
Sponsored by
Zhongshan Hospital Xiamen University
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

  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.

Sites / Locations

  • Zhongshan Hospital Xiamen UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

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

First Posted
October 8, 2019
Last Updated
October 16, 2019
Sponsor
Zhongshan Hospital Xiamen University
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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
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

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
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
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
No
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
Email
chenxiaomin0517@sina.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yuan Tian, assistant
Phone
8618250865805
Email
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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