Quercetin in Coronary Artery By-pass Surgery

Study Overview
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Brief Summary
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The purpose of this study is to test the anti-inflammatory and anti-senescence effects of quercetin during coronary artery by-pass graft surgery.

Detailed Description
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After being informed about the study and the potential risk, all patients giving written informed consent will be randomized in a double-blind manner (participant and investigators) on 1:1 ratio to receive quercetin (500 mg twice daily) or placebo (twice daily) starting 2 days before a coronary artery by-pass graft surgery and for the duration of their hospitalization but up to 10 days (i.e. up to 7 days post-surgery). Blood (5 ml) will be collected the first morning after recruitment (t-1), 24h post-surgery (t1), day 4 post-surgery (t2) and day of hospital discharge for blood analyses. During the surgery, if a discarded segment of mammary artery is available, it will be collected for laboratory work. Health status will be assessed during the follow-up visit 8 to 12 weeks post-surgery.

Official Title
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Étude randomisée contrôlée Par Placebo de Phase II Visant à Mesurer l'Effet Anti-inflammatoire et Anti-sénescence de la quercétine Lors d'Une Chirurgie Cardiaque

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Quercetin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: to be able to speak French or English; to be able to give free and enlighten consent; be hospitalized and waiting for a cardiac surgery of revascularization; to have had a myocardial infarction (MI) within the past 30 days or to be in a state of stable angina before the surgery. Exclusion Criteria: to be in a stable state without MI in the last 30 days; have a cardiac surgery concomitant to the cardiac surgery of revascularization; have an infection in the last 30 days; to have renal insufficiency (GFR less than 30); to have a liver disease (AST, ALT or bilirubin ˃ 2X normal values); to have a known cirrhosis; to have a past history of breast cancer or other tumors estrogen-dependent; to be intolerant to flavonoids, niacine or ascorbic acid; take quinolone; need for a quinolone during post-op; not being able to give a free and enlighten consent; not being able to speak French of English; take quercetin as a supplement.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Quercetin<br>Patients receiving 500 mg quercetin twice daily | Drug: Quercetin<br>* 500 mg twice daily<br>|
| Placebo Comparator: Placebo<br>Patients receiving placebo twice daily | Drug: Placebo<br>* twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quercetin-associated change in surgery-associated inflammation | Circulating blood levels of hs-CRP (mg/L) will be measured. | Baseline, 1 day and 4 days post-surgery | 
| Quercetin-associated change in surgery-associated marker of senescence | Circulating blood levels of ANGPTL2 (ng/L) will be measured. | Baseline, 1 day and 4 days post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quercetin-dependent change in endothelium-dependent relaxation | When available, a discarded segment of the mammary artery will be collected at the end of the cardiac surgery. One portion of the segment will be used to study the endothelium-dependent relaxation ex vivo. Segments will be mounted on a wire myograph. After an equilibration period, it will be pre-contracted with U46619 (0.1 µM): when the pre-contraction is stable, a cumulative dose-response curve to acetylcholine is built to induce an endothelium-dependent relaxation. Relaxation will be determined by two parameters, the vascular sensitivity to acetylcholine (µM) and the maximal relaxation induced by acetylcholine (% of relaxation). | During surgery | 
| Quercetin-dependent change in senescent endothelial cell load | When available, a discarded segment of the mammary artery will be collected at the end of the cardiac surgery. One portion of the segment will be used to isolate arterial wall cell nuclei for single nuclei mRNA sequencing. Senescence is assessed by expression levels of p21 mRNA, p16 mRNA and ANGPTL2 mRNA. | During surgery | 
| Quercetin-dependent change in senescent arterial wall cell load | When available, a discarded segment of the mammary artery will be collected at the end of the cardiac surgery. One portion of the segment will be stored at -80oC for bulk mRNA sequencing. Arterial wall senescence will be assessed by expression levels of p21 mRNA, p16 mRNA and ANGPTL2 mRNA. | During surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammation, Endothelium, Senescence, Vascular reactivity