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

Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06201000
• Other study ID #: IHC00068
• Status: Recruiting
• Start date: December 27, 2023
• Est. completion date: September 1, 2024

Study information

• Verified date: February 2024
• Source: October 6 University
• Contact: Ahmed Essam, MSc
• Phone: +201007647696
• Email: ahmed.essam[@]o6u.edu.eg
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 282
• Est. completion date: September 1, 2024
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Genetic Polymorphisms
• Heart Failure

Intervention

Drug:
• SGLT2 inhibitors (Dapagliflozin and Empagliflozin)
10 mg of dapagliflozin or empagliflozin

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (4)

Lead Sponsor	Collaborator
October 6 University	Beni-Suef University, National Heart Institute, Egypt, University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median / Mean of Left Ventricular Ejection Fraction (LVEF) among studied genetic polymorphisms	Change in median / mean of Left Ventricular Ejection Fraction (LVEF) before and after drug administration	6 months
Primary	Median / Mean of Left Ventricular End Systolic Volumes among studied genetic polymorphisms	Change in median / mean of Left Ventricular End Systolic Volume (LVESV)	6 months
Primary	Median / Mean of Left Ventricular End Diastolic Volumes among studied genetic polymorphisms	Change in median / mean of Left Ventricular End Diastolic Volume (LVEDV) before and after drug administration	6 months
Secondary	Median / Mean of quality of life measure {Kansas City Cardiomyopathy Questionnaire (KCCQ-12)} among studied genetic polymorphisms	Change in median / mean of Kansas City Cardiomyopathy Questionnaire (KCCQ-12) before and after drug administration	6 months