Coronary Artery Disease
Conditions
Keywords
Inflammation, Endothelium, Senescence, Vascular reactivity
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.
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.
Interventions
DRUGQuercetin
500 mg twice daily
DRUGPlacebo
twice daily
Sponsors
Montreal Heart Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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
Intervention model description
Randomized, double-blind, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 as well as a panel of circulating inflammatory markers in a subgroup of patients at day 5 post-surgery |
| 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 in addition to additional circulating markers of inflammation in a sub-group of patients at day 4 post-surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acetylcholine Concentration (nM) Required for EC50 in Endothelium-dependent Relaxation | During surgery | A discarded segment of the mammary artery will be collected at the end of the cardiac surgery when available. 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 the vascular sensitivity to acetylcholine (nM). IMPORTANT: at completion of the study, the analysis revealed that during the surgery, only 34 arterial segments from patients in the quercetin group and 44 segments from patients in the placebo group were made available by the surgeon. Therefore, only these 78 arterial segments were analyzed for this outcome measure of the ITT population (n=97). |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORMichel Carrier, MD
Montreal Heart Institute
Participant flow
Recruitment details
coronary unit patients waiting for CABG surgery
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 30 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 67 years STANDARD_DEVIATION 1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 97 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Inflammatory status (hs-CRP values) | 7.1 mg/L STANDARD_DEVIATION 1.8 |
| Region of Enrollment Canada | 50 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 47 |
| other Total, other adverse events | 0 / 50 | 0 / 47 |
| serious Total, serious adverse events | 0 / 50 | 0 / 47 |
Outcome results
None listed