Clinical trial NCT06201000: Effect of Genetic Polymorphisms on the Clinical Response to SGLT2 Inhibitors in Heart Failure Patients
Official title: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Genetic Polymorphisms
Heart Failure
Lead sponsor: October 6 University
Sponsor class: OTHER
Collaborators: name: University of Florida
name: National Heart Institute, Egypt
name: Beni-Suef University
First posted: 2024-01-11
Enrollment: 282
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Median / Mean of Left Ventricular Ejection Fraction (LVEF) among studied genetic polymorphisms
timeFrame: 6 months
measure: Median / Mean of Left Ventricular End Systolic Volumes among studied genetic polymorphisms
timeFrame: 6 months
measure: Median / Mean of Left Ventricular End Diastolic Volumes among studied genetic polymorphisms
timeFrame: 6 months
Secondary outcomes:
measure: Median / Mean of quality of life measure {Kansas City Cardiomyopathy Questionnaire (KCCQ-12)} among studied genetic polymorphisms
timeFrame: 6 months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: Beni-Suef University
name: Rania Sarhan, PhD
role: STUDY_DIRECTOR
affiliation: Misr International University
name: Neven Sarhan, PhD
role: STUDY_DIRECTOR
affiliation: National Heart Institute
name: Bassem Zarif, MD
role: STUDY_DIRECTOR
affiliation: University of Florida
name: Julio Duarte, PhD
role: STUDY_CHAIR
References: