Mechanisms Underlying SGLT2i Kidney Effect in DKD Progression

NCT07270198 | Not Yet Recruiting

• 1 other identifier: PERSONALISE-DKD
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicentre and multi-national non-pharmacological, uncontrolled interventional study conducted in a clinical practice setting in DKD patients with CKD stages 1 to 3 with moderate or severe risk of renal function decline in chronic treatment with SGLT2i. The main aim of the study is to assess the independent role of baseline individual mpMRI markers (hemodynamic, oxygenation, microstructure, perfusion, and fat fraction) and biochemical markers of MMP-related pathways (MMP-10 and TIMP-1) in the prediction of chronic eGFR decline in the above mentioned patients who are on chronic SGLT2i therapy.

Conditions

Diabetic Kidney Disease (DKD)

Outcome Measures

Primary Outcomes (8)

• Estimated glomerular filtration rate (eGFR)

  EGFR estimation by CKD-EPI and EKFC equations (ml/min)

  At day 0, at 1 month and at 18 months

• Matrix metalloproteases (MMPs) and their tissue inhibitors (TIMP)

  Serum levels of MMP-10 and TIMP-1 will be assessed in blood samples by commercial ELISA kits, according to the manufacturer's instructions (pg/ml)

  At day 0, at 1 month and at 18 months

• Multiparametric kidney MRI

  Total kidney, cortical and medullary volumes (in mL)

  At day 0, at 1 month and at 18 months

• Multiparametric kidney MRI

  Renal tissue oxygenation obtained by measuring the R2\* relaxation rate (in 1/ms)

  At day 0, at 1 month and at 18 months

• Multiparametric kidney MRI

  Apparent diffusion coefficient (in cm2/s)

  At day 0, at 1 month and at 18 months

• Multiparametric kidney MRI

  Renal tissue perfusion (in mL/100mL/min)

  At day 0, at 1 month and at 18 months

• Multiparametric kidney MRI

  Renal blood flow (in mL/min)

  At day 0, at 1 month and at 18 months

• Multiparametric kidney MRI

  T1 and T2 relaxation times (in ms)

  At day 0, at 1 month and at 18 months

Study Arms (1)

Patients

EXPERIMENTAL

Adult Diabetic Kidney Disease (DKD) patients with CKD stages 1 to 3 at moderate or severe risk of renal disease progression.

Procedure: MRI

Interventions

MRI PROCEDURE

Multiparametric non-contrast enhanced renal MRI and biochemical analysis to investigate MMP-related pathways (MMP-10 and TIMP-1 serum levels)

Patients

Eligibility Criteria

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

You may qualify if:

• male and female subjects aged ≥ 18 years;
• written informed consent prior to any study specific procedures
• type 2 Diabetes Mellitus with DKD
• CKD stage 1 to 3 (eGFR\>30 ml/min) with moderate or severe risk of renal disease progression (according to KDIGO 2024 CKD guidelines, G1 and G2 with albuminuria \>300 mg/g, G3a with albuminuria \>30 mg/g, and G3b independently of albuminuria levels)
• ongoing SGLT2i treatment (e.g. canagliflozin, empagliflozin or dapagliflozin) for at least 1 year and stable RAS inhibitor therapy with ACE inhibitors and/or ARBs (or without RAS inhibitors in patients with specific contraindications for this medication)

You may not qualify if:

• Uncontrolled diabetes (glycated hemoglobin (A1C) \> 8%; 64 mmol/mol)
• Contraindications to MRI including claustrophobia, pregnancy or lactating, cardiac pacemakers, or other MRI-incompatible prostheses, or impossibility to perform MRI
• Any chronic clinical condition (e.g. history of malignancy) other than CKD and related complications that could affect completion of the trial or confound data interpretation
• Non-diabetic CKD: CKD highly suspected to be related with a different renal condition other than Diabetes Mellitus as the cause of CKD (i.e. glomerular disease, tubulo-interstitial nephritis, microangiopathic thrombotic disease, renovascular/ischemic kidney disease, etc)
• Active systemic autoimmune diseases
• Concomitant treatment with steroids or any other immunosuppressive agent
• Chronic heart failure with New York Heart Association class III-IV at the screening visit
• Intention to become pregnant in the following 2 years (female patients)
• Drug or alcohol abuse

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (1)

Clinical Research Centre for Rare Diseases Aldo e Cele Daccò

Ranica, BG, 24020, Italy

Location

MeSH Terms

Conditions

Diabetic Nephropathies

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Giuseppe Remuzzi, M.D.

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY DIRECTOR

Central Study Contacts

Anna Caroli, PhD

CONTACT

+390354535381; anna.caroli@marionegri.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: December 8, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: December 8, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)