Resveratrol for Coronary Artery Disease

(SIRT-CVS Trial)

Overseen By Douglas Sawyer, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: MaineHealth

Must be taking: Oral agents, Insulin

Disqualifiers: Heart failure, Liver dysfunction, Renal dysfunction, Alcohol use, others

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial includes patients with type 2 diabetes controlled by oral agents or insulin, it seems likely that you can continue those medications.

What data supports the effectiveness of the drug resveratrol for coronary artery disease?

Research suggests that resveratrol, a compound found in grapes and red wine, may protect the heart by improving blood flow and reducing heart damage in animal models. It has shown potential benefits in preventing heart problems and improving heart health in humans, although more research is needed to confirm its effectiveness for coronary artery disease specifically. ^{1 2 3 4 5}

Is resveratrol safe for human use?

Resveratrol has been found to be safe and reasonably well-tolerated in humans at doses up to 5 grams per day, although mild to moderate side effects may occur, suggesting future trials will use lower doses. ^{2 4 6 7 8}

How does the drug trans-resveratrol differ from other treatments for coronary artery disease?

Trans-resveratrol is unique because it is a natural compound found in red wine and other plants, known for its antioxidant and anti-inflammatory properties. Unlike traditional treatments, it may improve heart health by protecting against oxidative stress and enhancing blood flow in the heart, potentially offering a novel approach to managing coronary artery disease. ^{2 4 6 9 10}

What is the purpose of this trial?

Major Problem People with diabetes have an increased risk of heart disease, heart failure, and death from a cardiovascular cause. Diabetes prevents efficient metabolism of fuel, causes inflammation and vascular disease that blocks normal blood flow, and inhibits the function of the heart after injury. These changes make diabetics more susceptible to heart attacks and heart failure. Resveratrol is found in grapes and red wine and has been shown to have beneficial effects in diabetic patients. In previous studies the investigators have shown that resveratrol can improve heart metabolism and function in pigs with diabetes and chronic lack of blood flow to the heart. Questions The investigators believe resveratrol will help reverse the negative effects of diabetes on the heart. The questions are: 1.How does the molecular machinery in the hearts of patients with diabetes differ from patients without diabetes? 2.Will resveratrol have an effect on heart metabolism, intracellular signaling, inflammation and blood vessel function? 3.Will resveratrol improve the number and function of cardiac stem cells, cells involved in heart repair? The investigators have been safely collecting tissue from the hearts of patients undergoing heart surgery. Preliminary studies show the investigators can isolate and study cells. The investigators have collected and assessed the function of endothelial cells, a measure of vascular health and can measure the level of endothelial injury and have studied the make-up of caveolae, structures on the cell membrane that are important for cell signaling and are negatively impacted by diabetes. This study is a unique collaboration among cardiologists, cardiac surgeons, and basic scientists.

Research Team

Douglas Sawyer

Principal Investigator

Maine Health

Eligibility Criteria

Adults over 18 with Type 2 diabetes and coronary artery disease scheduled for elective heart bypass surgery can join. They must not have severe kidney, liver, or blood clotting issues, be pregnant, or have certain infections like HIV. Heavy drinkers and those unlikely to follow the study plan are excluded.

Inclusion Criteria

You have type 2 diabetes that is managed with pills or insulin.

You have coronary artery disease and are scheduled for elective coronary artery bypass grafting with cardiopulmonary bypass.

Exclusion Criteria

Your blood clotting tests show abnormal results.

Patients who are pregnant

Your liver function tests show results more than two times the normal range.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive resveratrol or placebo during coronary artery bypass grafting with cardiopulmonary bypass

14 days

Follow-up

Participants are monitored for changes in endothelial function and molecular signaling

4 weeks

Treatment Details

Interventions

• Placebo
• Trans-resveratrol

Trial Overview The trial is testing if resveratrol (found in grapes/red wine) can improve heart health in diabetics by comparing it against a placebo. It looks at how it affects heart metabolism, inflammation, blood vessel function, and cardiac repair cells.

Participant Groups

Group I: Resveratrol Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

MaineHealth

Lead Sponsor

Trials

76

Recruited

43,800+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Findings from Research

Cis-resveratrol significantly reduces collagen-induced platelet aggregation in vitro, with a decrease of 43.5% at a concentration of 1 x 10(-5) M, indicating its potential as an anti-aggregating agent.

Trans-resveratrol also shows anti-aggregating effects but is slightly less effective than cis-resveratrol, suggesting that both isomers should be considered when evaluating resveratrol's overall activity in biological systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiplatelet activity of cis-resveratrol. Bertelli, AA., Giovannini, L., Bernini, W., et al.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Resveratrol induces nuclear factor-κB activity in human cardiac cells. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Resveratrol and cardiovascular health--promising therapeutic or hopeless illusion? [2018]

3. Brazil pubmed.ncbi.nlm.nih.gov

Cardioprotection stimulated by resveratrol and grape products prevents lethal cardiac arrhythmias in an animal model of ischemia and reperfusion. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Resveratrol in primary and secondary prevention of cardiovascular disease: a dietary and clinical perspective. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pharmacological basis and new insights of resveratrol action in the cardiovascular system. [2021]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The Cardiovascular Nutrapharmacology of Resveratrol: Pharmacokinetics, Molecular Mechanisms and Therapeutic Potential [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Clinical trials of resveratrol. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Antiplatelet activity of cis-resveratrol. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. [2022]