Expression of Sodium-glucose Co-transporter 2 in Human Heart

Aortic Valve Stenosis Clinical Trial

— SGLT2-MICRA  

Official title:

Expression of Sodium Glucose Co-transporter2 in Myocardium From Patients With Aortic Valve Stenosis and With/Without Diastolic Heart Failure

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05830760
• Other study ID #: 8774
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2023
• Est. completion date: October 2025

Study information

• Verified date: April 2023
• Source: University Hospital, Strasbourg, France
• Contact: Jean Philippe MAZZUCOTELLI, Professor
• Phone: 369555703
• Email: Jean-Philippe.MAZZUCOTELLI[@]chru-strasbourg.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to evaluate the expression of Sodium Glucose Co-transporter 2 (SGLT2) in myocardium from patients with aortic stenosis. 2 groups of patients will be defined: Group A with diastolic heart failure and Group B without heart failure. The expression of SGLT2 will be measured on small myocardium specimens harvested during aortic valve replacement operation. This study should allow us to better understand the effect of glifozines in human heart failure.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: October 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adults over 18 years-old
• Patient with surgical aortic valve stenosis, with or without heart failure, in two equal-sized groups (40 subjects in each group)
• Subjects affiliated with a social security health insurance plan
• Subject able to understand the objectives and risks of the research and to give dated and signed informed consent

Exclusion Criteria:

• Infective endocarditis in aortic stenosis
• Severe coronary pathology associated with aortic stenosis
• Impossible to give the subject informed information (subject in emergency situation, difficulties in understanding the subject, ...)
• Subject under legal protection
• Subject under guardianship or curatorship
• Pregnancy and/or breastfeeding

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic

Intervention

Biological:
• Myocardium biopsy
The expression of SGLT2 on small myocardium specimens harvested during aortic valve replacement operation in patients with aortic stenosis

Locations

Country	Name	City	State
France	Hôpitaux Universitaires de Strasbourg	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Strasbourg, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To study the expression levels of SGLT2 in the myocardium of patients with surgical aortic stenosis	Measure of SGLT2 expression level by RT-PCR and	Day 0
Primary	To study the SGLT2 tissue localization in the myocardium of patients with surgical aortic stenosis	SGLT2 expression level by immunofluorescence labeling	Day 0
Secondary	Comparison of SGLT2 expression levels between heart failure and non-heart failure patients.	SGLT2 expression levels between the 2 groups of patients	Day 0
Secondary	Assess oxidative stress	Pro-oxidant response (fluorescence level of the redox-sensitive fluorescent probe DHE)	Day 0
Secondary	Evaluate the pro-inflammatory response by analysing the expression level of tissue activation molecules VCAM-1, ICAM-1, MCP-1	Pro-inflammatory response: (VCAM-1, ICAM-1, MCP-1). Expression level of tissue activation molecules VCAM-1, ICAM-1, MCP-1 by RT-PCR, Western blot analysis and immunofluorescence labeling	Day 0
Secondary	Evaluate the pro-fibrotic response	Pro-fibrotic response: TGF beta, Ang II, AT1R, ACE, collagen; MMP-2, MMP-9. Expression level of molecules involved in tissue remodeling TGF beta, Ang II, AT1R, ACE, collagen, MMP-2, MMP-9 by RT-PCR, Western blot analysis and immunofluorescence labeling	Day 0
Secondary	Evaluate the pro-senescent response	Pro-senescent response: SA-beta-galactosidase activity, p53, p21, P16. Determination of senescence-associated beta-galactosidase activity on cardiac muscle cryosections, and expression level of senescence mediators p53, p21, p16 by RT-PCR, Western blot analysis and immunofluorescence labeling	Day 0
Secondary	Evaluate the pro-thrombotic response	Pro-thrombotic response: tissue factor. Expression level of coagulation cascade activator, tissue factor by RT-PCR, Western blot analysis and immunofluorescence labeling	Day 0
Secondary	Evaluate endothelial dysfunction	Endothelial response: eNOS, NO, nitrotyrosine. Expression level of eNOS and nitrotyrosine by RT-PCR, Western blot analysis and immunofluorescence labeling and NO formation using the NO-sensitive fluorescent probe, DAF-FM on heart muscle cryosections	Day 0