Effect of Genetic Polymorphisms on the Clinical Response to SGLT2 Inhibitors in Heart Failure Patients

February 6, 2024 updated by: Ahmed Essam, October 6 University

Effect of Genetic Polymorphisms on the Clinical Response to Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors in Prevention of Cardiac Remodeling and Fibrosis in Heart Failure Patients

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown further reductions in heart failure hospitalization, cardiovascular events, and mortality, especially for heart failure patients.

The SGLT2 gene, also known as SLC5A2 (solute carrier family 5 member 2), is located on chromosome 16 and is responsible for encoding SGLT2.

Several SLC5A2 mutations alter SGLT2 expression, membrane location, or transporter function.

Several common genetic variations were found in the SLC5A2 gene that may affect the response to treatment with SGLT2 inhibitors.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i), which were first investigated and licensed for the treatment of diabetes, are now emerging as a promising class of drugs for the treatment of heart failure (HF), even in people without diabetes.

Significant reductions in worsening heart failure or cardiovascular death were shown under treatment with dapagliflozin and empagliflozin in the trials of patients with heart failure.

Several common genetic variations were found in the SLC5A2 gene that may affect the response to treatment with SGLT2 inhibitors.

The most recent SLC5A2 Single Nucleotide Polymorphisms (SNPs) that reduce the risk of heart failure included two intronic SLC5A2 SNPs, s9934336, and rs3116150, both associated with the expression levels of the transporter.

This study aims to detect the association between SLC5A2 single nucleotide polymorphisms and variability in response to SGLT2 Inhibitors as well as the association between cardiac biomarkers and non-coding RNA in patients with Heart Failure.

Study Type

Observational

Enrollment (Estimated)

282

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 Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • University of Florida
        • Contact:
          • Julio Duarte, PhD

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 study population consist of established Heart failure with reduced ejection fraction (HFrEF) or Heart failure with preserved ejection fraction (HFpEF) and New York Heart Association (NYHA) functional classes II-III, who will be candidates for add-on treatment with SGLT2i.

Description

Inclusion Criteria:

  • Heart failure patients NYHA class II to III.
  • Heart failure patients with reduced left ventricular ejection fraction (LVEF) < 45% or with preserved left ventricular ejection fraction (LVEF) > 45%
  • Patients who will be candidate for add-on treatment with SGLT2.
  • Patients who will be able to sign informed consent to participate in the study.

Exclusion Criteria:

  • Contraindications to SGLT2.
  • Significant coronary artery diseases (CAD), coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or valve surgery within 3 months.
  • Pregnant or breastfeeding women.
  • Patients with estimated glomerular filtration rates less than 30 mL/min/1.73 m2, as determined using the CKD-EPI equation.

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
Heart Failure Patients with reduced or preserved Ejection Fraction
Patients with reduced or preserved ejection fraction that have received the Guided Therapy (β-blockers, Diuretics, Angiotensin-converting enzyme (ACE) inhibitors or Angiotensin receptor blockers (ARBs) or Angiotensin Receptor-Neprilysin Inhibitor (ARNi) and Mineralocorticoid receptor antagonists (MRAs) then Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) (10 mg of dapagliflozin or empagliflozin) will be added at the study entry.
Drug: SGLT2 inhibitors (Dapagliflozin and Empagliflozin)
10 mg of dapagliflozin or empagliflozin
Other Names:
  • Forxiga
  • Jardiance

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median / Mean of Left Ventricular Ejection Fraction (LVEF) among studied genetic polymorphisms
Time Frame: 6 months
Change in median / mean of Left Ventricular Ejection Fraction (LVEF) before and after drug administration
6 months
Median / Mean of Left Ventricular End Systolic Volumes among studied genetic polymorphisms
Time Frame: 6 months
Change in median / mean of Left Ventricular End Systolic Volume (LVESV)
6 months
Median / Mean of Left Ventricular End Diastolic Volumes among studied genetic polymorphisms
Time Frame: 6 months
Change in median / mean of Left Ventricular End Diastolic Volume (LVEDV) before and after drug administration
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median / Mean of quality of life measure {Kansas City Cardiomyopathy Questionnaire (KCCQ-12)} among studied genetic polymorphisms
Time Frame: 6 months
Change in median / mean of Kansas City Cardiomyopathy Questionnaire (KCCQ-12) before and after drug administration
6 months

Collaborators and Investigators

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

Sponsor

October 6 University

Collaborators

University of Florida
Beni-Suef University
National Heart Institute, Egypt

Investigators

  • Study Director: Rania Sarhan, PhD, Beni-Suef University
  • Study Director: Neven Sarhan, PhD, Misr International University
  • Study Director: Bassem Zarif, MD, National Heart Institute
  • Study Chair: Julio Duarte, PhD, University of Florida

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)

December 27, 2023

Primary Completion (Estimated)

July 1, 2024

Study Completion (Estimated)

September 1, 2024

Study Registration Dates

First Submitted

December 27, 2023

First Submitted That Met QC Criteria

January 10, 2024

First Posted (Actual)

January 11, 2024

Study Record Updates

Last Update Posted (Estimated)

February 7, 2024

Last Update Submitted That Met QC Criteria

February 6, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IHC00068

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.

Yes

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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