Type 2 DiabetesPhase 4NCT04127084
Effects of SGLT2 Inhibition Treatment on Different Levels of Albuminuria in Patients With Type 2 Diabetes
A Phase 4 study testing SGLT2 Inhibition in people with Type 2 Diabetes and Diabetic Nephropathy, run by Zhongshan Hospital Xiamen University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Type 2 Diabetes, Diabetic Nephropathy
- What is being tested?
- SGLT2 Inhibition
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteChina
- Study dates
- 15 Oct 2019to Aug 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhongshan Hospital Xiamen University
Xiamen, Fujian, 361004
Yi-lin Zhao, principle, 8613950085931
Xiao-min Chen, principle
About this study
Official title: Effects of SGLT2 Inhibition Treatment on Different Levels of Albuminuria in Patients With Type 2 Diabetes: a Prospective Interventional Study
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.
Read the 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
- Being tested
- SGLT2 Inhibition
- Keywords
- Type 2 diabetes, Diabetic Nephropathy, Albuminuria, SGLT2 inhibitor
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetic Nephropathies, Albuminuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SGLT2 InhibitionDrug
Also called Dapagliflozine,Empagliflozin,Canagliflozin
Dapagliflozine 5-10 mg once daily tablet treatment or Empagliflozin10 mg once daily tablet treatment or Canagliflozin 100 mg once daily tablet treatment
| Study group | Role | What they receive |
|---|---|---|
| normal albuminuria | Experimental | baseline urinary albumin creatinine ratio [UACR]< 30 mg/g Receives: Drug: SGLT2 Inhibition |
| moderately increased albuminuria | Experimental | baseline UACR 30~300 mg/g Receives: Drug: SGLT2 Inhibition |
| severely increased albuminuria | Experimental | baseline UACR>300mg/g Receives: Drug: SGLT2 Inhibition |
| blank Comparator | No intervention | normal participant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Up to 12 weeks
Change in eGFR
eGFR was calculated by modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: Up to 12 weeks
changes of AGEs
To evaluate the effects of SGLT2 inhibition treatment on oxidative stress index, the changes of AGEs.
Measured: 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
Measured: Up to 12 weeks
Secondary outcomes (4)
Change in uric acid
To evaluate the levels of serum uric acid before and after SGLT2 inhibition treatment.
Measured: Up to 12 weeks
Change in aldosterone
To evaluate the levels of aldosterone before and after SGLT2 inhibition treatment.
Measured: Up to 12 weeks
Change in rennin
To evaluate the levels of rennin before and after SGLT2 inhibition treatment
Measured: Up to 12 weeks
Change in angiotensin
To evaluate the levels of angiotensin before and after SGLT2 inhibition treatment
Measured: Up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2019
- Study start15 Oct 2019
- Primary completionOct 2020 (estimated)
- Study completionAug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhongshan Hospital Xiamen University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yi-lin Zhao, principal, Study director, Zhongshan Hospital Xiamen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04127084
- Sponsor's protocol ID
- 20191005
- Status last verified
- Oct 2019
- First submitted
- 8 Oct 2019
- Last updated
- 21 Oct 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38365853Tian 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.
PubMed 36127497
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of SGLT2 Inhibition Treatment on Different Levels of Albuminuria in Patients With Type 2 Diabetes: a Prospective Interventional Study
- ClinicalTrials.gov ID
- NCT04127084
- Acronym / sponsor ID
- 20191005
- Conditions
- Type 2 Diabetes, Diabetic Nephropathy
- Keywords
- Type 2 diabetes, Diabetic Nephropathy, Albuminuria, SGLT2 inhibitor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Zhongshan Hospital Xiamen UniversityUniversity, hospital or other
- Study start
- 15 Oct 2019 (actual)
- Primary completion
- Oct 2020 (estimated)
- Study completion
- Aug 2021 (estimated)
- First posted
- 15 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| normal albuminuria | Experimental | Drug: SGLT2 Inhibitionbaseline urinary albumin creatinine ratio [UACR]< 30 mg/g |
| moderately increased albuminuria | Experimental | Drug: SGLT2 Inhibitionbaseline UACR 30~300 mg/g |
| severely increased albuminuria | Experimental | Drug: SGLT2 Inhibitionbaseline UACR>300mg/g |
| blank Comparator | No intervention | –normal participant |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SGLT2 InhibitionAlso: Dapagliflozine,Empagliflozin,CanagliflozinDapagliflozine 5-10 mg once daily tablet treatment or Empagliflozin10 mg once daily tablet treatment or Canagliflozin 100 mg once daily tablet treatment | Drug | moderately increased albuminuria, normal albuminuria, severely increased albuminuria |
Primary outcome
Change in urinary albuminuria
Time frame: Up to 12 weeks
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
Time frame: Up to 12 weeks
eGFR was calculated by modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease.
change in nephrin
Time frame: Up to 12 weeks
To assess effect of SGLT2 inhibition intervention on glomerular podocyte injury by detecting the expression of renal nephrin.
change in TGF-β1
Time frame: Up to 12 weeks
To assess effect of SGLT2 inhibition intervention on glomerular and tubulointerstitial fibrosis by detecting the expression of TGF-β1
change in IL-6
Time frame: Up to 12 weeks
To assess effect of SGLT2 inhibition intervention on inflammation biomarkers by detecting the levels of interleukin-6.
change in TNFα
Time frame: Up to 12 weeks
To evaluate the effects of SGLT2 inhibition treatment on inflammation, biomarkers by detecting the levels of tumor necrosis factor alpha.
changes of AGEs
Time frame: Up to 12 weeks
To evaluate the effects of SGLT2 inhibition treatment on oxidative stress index, the changes of AGEs.
changes of 8-OH-dG
Time frame: Up to 12 weeks
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
4 secondary outcomes
Change in uric acid
Time frame: Up to 12 weeks
Change in aldosterone
Time frame: Up to 12 weeks
Change in rennin
Time frame: Up to 12 weeks
Change in angiotensin
Time frame: Up to 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2019.
- Derived from this study: PubMed 38365853Zeng 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.
- Derived from this study: PubMed 36127497Tian 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yi-lin Zhao, principal study director
Zhongshan Hospital Xiamen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing SGLT2 Inhibition in people with Type 2 Diabetes and Diabetic Nephropathy, run by Zhongshan Hospital Xiamen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiao-min Chen, principal (8613860487599, chenxiaomin0517@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in urinary albuminuria (time frame: Up to 12 weeks). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04127084, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2019.