Q-CABG: Quercetin in Coronary Artery By-pass Surgery

Sponsor

Montreal Heart Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04907253

Collaborator

(none)

100

Enrollment

Location

Arms

23.9

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Quercetin Drug: Placebo	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, double-blind, placebo-controlledRandomized, double-blind, placebo-controlled

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Allocation of randomization numbers by the pharmacist provided as a randomization list prepared by the biostatisticians of the Montreal Heart Institute

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 4, 2021

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Quercetin Patients receiving 500 mg quercetin twice daily	Drug: Quercetin 500 mg twice daily
Placebo Comparator: Placebo Patients receiving placebo twice daily	Drug: Placebo twice daily

Arm

Intervention/Treatment

Active Comparator: Quercetin

Patients receiving 500 mg quercetin twice daily

Drug: Quercetin

500 mg twice daily

Placebo Comparator: Placebo

Patients receiving placebo twice daily

Drug: Placebo

twice daily

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Quercetin-dependent change in endothelium-dependent relaxation [During surgery]
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).
Quercetin-dependent change in senescent endothelial cell load [During surgery]
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.
Quercetin-dependent change in senescent arterial wall cell load [During surgery]
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.

Other Outcome Measures

Health status at follow-up visit. [8 to 12 weeks post-surgery]
During the follow-up visit, routine patient questioning will be performed and medical file will be reviewed for noticeable change in health status.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.