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

NCT04127084 | Unknown Phase 4

• 1 other identifier: 20191005
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes; Diabetic Nephropathy

Keywords

Type 2 diabetes; Diabetic Nephropathy; Albuminuria; SGLT2 inhibitor

Outcome Measures

Primary Outcomes (8)

• 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)

  Up to 12 weeks

• Change in eGFR

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

  Up to 12 weeks

• change in nephrin

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

  Up to 12 weeks

• change in TGF-β1

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

  Up to 12 weeks

• change in IL-6

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

  Up to 12 weeks

• change in TNFα

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

  Up to 12 weeks

• changes of AGEs

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

  Up to 12 weeks

• 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

  Up to 12 weeks

Secondary Outcomes (4)

• Change in uric acid

  Up to 12 weeks

• Change in aldosterone

  Up to 12 weeks

• Change in rennin

  Up to 12 weeks

• Change in angiotensin

  Up to 12 weeks

Study Arms (4)

normal albuminuria

EXPERIMENTAL

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

Drug: SGLT2 Inhibition

moderately increased albuminuria

EXPERIMENTAL

baseline UACR 30\~300 mg/g

Drug: SGLT2 Inhibition

severely increased albuminuria

EXPERIMENTAL

baseline UACR\>300mg/g

Drug: SGLT2 Inhibition

blank Comparator

NO INTERVENTION

normal participant

Interventions

SGLT2 Inhibition DRUG

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

Also known as: Dapagliflozine,Empagliflozin,Canagliflozin

moderately increased albuminuria; normal albuminuria; severely increased albuminuria

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Zhongshan Hospital Xiamen University: lead

Study Sites (1)

Zhongshan Hospital Xiamen University

Xiamen, Fujian, 361004, China

RECRUITING

Related Publications (2)

• 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.

  PMID: 38365853 DERIVED

• 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.

  PMID: 36127497 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetic Nephropathies; Albuminuria

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Proteinuria; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Yi-lin Zhao, principal

  Zhongshan Hospital Xiamen University

  STUDY DIRECTOR

Central Study Contacts

Xiao-min Chen, principal

CONTACT

8613860487599; chenxiaomin0517@sina.com

Yuan Tian, assistant

CONTACT

8618250865805; 411954353@qq.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2019
• First Posted: October 15, 2019
• Study Start: October 15, 2019
• Primary Completion: October 1, 2020
• Study Completion: August 1, 2021
• Last Updated: October 21, 2019

Record last verified: 2019-10

Locations

CN (1)