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Expression of Sodium-glucose Co-transporter 2 in Human Heart (SGLT2-MICRA)

Primary Purpose

Aortic Valve Stenosis

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Myocardium biopsy
Sponsored by
University Hospital, Strasbourg, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Aortic Valve Stenosis focused on measuring human heart, myocardium, aortic valve stenosis, heart failure, sodium glucose cotransporter 2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hôpitaux Universitaires de Strasbourg

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

patients with aortic valve stenosis with heart failure

patients with aortic valve stenosis without heart failure

Arm Description

Outcomes

Primary Outcome Measures

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
To study the SGLT2 tissue localization in the myocardium of patients with surgical aortic stenosis
SGLT2 expression level by immunofluorescence labeling

Secondary Outcome Measures

Comparison of SGLT2 expression levels between heart failure and non-heart failure patients.
SGLT2 expression levels between the 2 groups of patients
Assess oxidative stress
Pro-oxidant response (fluorescence level of the redox-sensitive fluorescent probe DHE)
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
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
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
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
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

Full Information

First Posted
March 24, 2023
Last Updated
April 13, 2023
Sponsor
University Hospital, Strasbourg, France
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1. Study Identification

Unique Protocol Identification Number
NCT05830760
Brief Title
Expression of Sodium-glucose Co-transporter 2 in Human Heart
Acronym
SGLT2-MICRA
Official Title
Expression of Sodium Glucose Co-transporter2 in Myocardium From Patients With Aortic Valve Stenosis and With/Without Diastolic Heart Failure
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 2023 (Anticipated)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Strasbourg, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aortic Valve Stenosis
Keywords
human heart, myocardium, aortic valve stenosis, heart failure, sodium glucose cotransporter 2

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
patients with aortic valve stenosis with heart failure
Arm Type
Experimental
Arm Title
patients with aortic valve stenosis without heart failure
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Myocardium biopsy
Intervention Description
The expression of SGLT2 on small myocardium specimens harvested during aortic valve replacement operation in patients with aortic stenosis
Primary Outcome Measure Information:
Title
To study the expression levels of SGLT2 in the myocardium of patients with surgical aortic stenosis
Description
Measure of SGLT2 expression level by RT-PCR and
Time Frame
Day 0
Title
To study the SGLT2 tissue localization in the myocardium of patients with surgical aortic stenosis
Description
SGLT2 expression level by immunofluorescence labeling
Time Frame
Day 0
Secondary Outcome Measure Information:
Title
Comparison of SGLT2 expression levels between heart failure and non-heart failure patients.
Description
SGLT2 expression levels between the 2 groups of patients
Time Frame
Day 0
Title
Assess oxidative stress
Description
Pro-oxidant response (fluorescence level of the redox-sensitive fluorescent probe DHE)
Time Frame
Day 0
Title
Evaluate the pro-inflammatory response by analysing the expression level of tissue activation molecules VCAM-1, ICAM-1, MCP-1
Description
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
Time Frame
Day 0
Title
Evaluate the pro-fibrotic response
Description
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
Time Frame
Day 0
Title
Evaluate the pro-senescent response
Description
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
Time Frame
Day 0
Title
Evaluate the pro-thrombotic response
Description
Pro-thrombotic response: tissue factor. Expression level of coagulation cascade activator, tissue factor by RT-PCR, Western blot analysis and immunofluorescence labeling
Time Frame
Day 0
Title
Evaluate endothelial dysfunction
Description
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
Time Frame
Day 0

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jean Philippe MAZZUCOTELLI, Professor
Phone
369555703
Ext
0033
Email
Jean-Philippe.MAZZUCOTELLI@chru-strasbourg.fr
Facility Information:
Facility Name
Hôpitaux Universitaires de Strasbourg
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean Philippe MAZZUCOTELLI, Professor
Phone
369555703
Ext
0033
Email
Jean-Philippe.MAZZUCOTELLI@chru-strasbourg.fr

12. IPD Sharing Statement

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

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