Role of Sodium-glucose Linked Transporter 2 (SGLT2) and Its Inhibitor Over CARdiotoxicity Induced by Anthracyclines and Breast Cancer Tumorigenesis SCARA-B (SCARA-B)

February 2, 2026 updated by: Centre Paul Strauss

Role of Sodium-glucose Linked Transporter 2 (SGLT2) and Its Inhibitor Over CARdiotoxicity Induced by Anthracyclines and Breast Cancer Tumorigenesis - SCARA-B

In the context of breast cancer, in case of an indication for chemotherapy, anthracycline-based protocols make it possible to improve the overall survival of patients most at risk. The frequency of anthracycline-related cardiac toxicities (ARCT) increases with the cumulative dose of anthracyclines administered and explains, at least in part, the increased risk of cardiovascular (CV) mortality in patient populations treated for breast cancer. The numerous indications for anthracycline-based protocols have made it possible to describe ARCT, among which heart failure with reduced left ventricular ejection fraction (LVEF) remains one of the most comorbid. In addition to left ventricular dysfunction, anthracyclines have been associated with endothelial dysfunction, microvascular damage and myocardial ischemia responsible for dilated cardiomyopathy.

Different approaches have attempted to better understand and prevent these ARCT. However, apart from the notion of limit cumulative doses of anthracyclines, few of them have made it possible to screen patients at risk and prevent the onset of cardiac dysfunction. The search for biological markers (Troponin I, BNP) or ultrasound markers (Longitudinal Strain) warning of subclinical cardiac damage is still struggling to assert its interest due in particular to significant inter- and intra-observer variability. Therapeutically, ACE inhibitors and beta-blockers have shown a significant improvement in the incidence rate of LVEF reduction during adjuvant treatment of breast cancer. However, despite equivalent signals in other cancers, the studies conducted to date are insufficiently powered and the role of these treatments is limited to secondary prevention or the treatment of objective heart failure. It remains necessary to determine new biological markers that can identify patients most at risk of ARCT and thus adapt our therapeutic prevention strategies. To do this, it is first necessary to better understand the pathophysiology underlying these ARCT.

The objective of this study is to determine whether expression of the receptor among endothelium and circulating cells, SGLT2, is associated with an additional risk of presenting cardiovascular toxicity following treatment with anthracycline. If this association is demonstrated, it will then be possible to better screen and prevent these cardiovascular complications.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

The recruited population concerns adult patients followed for localized breast cancer and for whom treatment with anthracycline is indicated in the adjuvant or neoadjuvant situation.

Description

Inclusion Criteria:

  • Patient > 18 years old
  • Diagnosed with localized breast cancer
  • Indication for first-line surgery or anthracycline-based chemotherapy.

Exclusion Criteria:

  • History of chemotherapy or targeted therapy or immunotherapy administered before inclusion
  • Patient currently being treated with anti-SGLT2, conversion enzyme inhibitor or ARA2
  • Patient with known heart disease (ischemic, rhythmic, valvular, etc.)
  • Patient with a Glomerular filtration rate < 45 mL/min/1.73m² according to the pre-therapeutic assessment
  • Patient with impaired liver function
  • Patient who is pregnant or breastfeeding
  • Patient with a second cancer undergoing treatment
  • Patient under guardianship or curatorship, protection of justice or deprived of liberty

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Adjuvant scheme
Indication for anthracycline-based chemotherapy after first-line surgery
Drug: Anthracycline
as standard of care
Neoadjuvant scheme
Indication for anthracycline-based chemotherapy
Drug: Anthracycline
as standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the expression of SGLT2
Time Frame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Measurement of protein expression (Western Blot) and mRNA (RT-qPCR) of SGLT2 within the different models studied and according to the cumulative quantity of anthracyclines received and the patient's cardiovascular history before and after epirubine infusion.
At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Evaluate the expression of SGLT2
Time Frame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Measurement of the polarization of peripheral blood mononuclear cells (PBMCs) into pro-inflammatory M1 and anti-inflammatory M2 before and after epirubine infusion.
At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Evaluate the expression of SGLT2
Time Frame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Fluorescence measurement of the level of reactive oxygen species (ROS) formation and senescence of cardiovascular cells before and after epirubine infusion.
At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Evaluate the expression of SGLT2
Time Frame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Measurement of inflammatory mediators secreted by circulating cells.Comparison with positive and negative controls that induce inflammation and ROS before and after epirubine infusion.
At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the ex vivo functional impact at the endothelial and cardiac level of exposure to patient plasma during treatment
Time Frame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Measurement of the antiplatelet activity of endothelial celles (ECs) mediated by nitric oxide (NO), the procoagulant activity and the adhesion of platelets and monocytes to ECs before and after epirubine infusion.
At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Evaluate the ex vivo functional impact at the endothelial and cardiac level of exposure to patient plasma during treatment
Time Frame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Quantification of inflammatory mediators in plasma and produced by treated cardiovascular cells before and after epirubine infusion.
At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Paul Strauss

Collaborators

Centre de Recherche en biomédecine de Strasbourg INSERM UMR-S1118

Investigators

  • Principal Investigator: Hervé BISCHOFF, Centre Paul Strauss

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 17, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

May 13, 2024

First Submitted That Met QC Criteria

May 29, 2024

First Posted (Actual)

June 5, 2024

Study Record Updates

Last Update Posted (Actual)

February 4, 2026

Last Update Submitted That Met QC Criteria

February 2, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-024

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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