Clinical trial NCT05808387: The Effects of Resveratrol on Sirtuins and Apoptosis Biomarkers
Official title: The Effects of Resveratrol on Inhibitors of Apoptosis Proteins, on Soluble Receptors of Advanced Glycation End Products and on Sirtuins-1 and -3 in Postmenopausal Women With Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Menopause
Endothelial Dysfunction
Keywords: Coronary artery disease
Menopause
Endothelial Dysfunction
Sirtuin
Receptors of advanced glycation end products
Apoptosis
Resveratrol
Polyphenols
Cardiovascular risk
Lead sponsor: InCor Heart Institute
Sponsor class: OTHER
First posted: 2023-04-11
Enrollment: 80
Sex: FEMALE
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind randomized controlled trial, parallel and placebo-controlled.
Primary purpose: TREATMENT

Brief summary: Cardiovascular diseases (CVD) and neoplasms are the main causes of death in Brazilian women. Coronary artery disease (CAD) and stroke were responsible for approximately 54% of deaths from CVD in this population. In Brazil, cancers were the second cause of death and in 2017 were responsible for 58% of deaths in women. CVD and cancer share some risk factors, and control of these factors is associated with a significant reduction in cancer incidence. These two causes of death, although apparently disparate, share similar lifestyles and health risk factors, suggesting some common pathways and basic molecular networks. In women, the presence of estrogen has protective effects against atherosclerosis and, with the decline in hormone production at menopause, the incidence and prevalence of CAD increase substantially. Although the estrogen pathway is supposed to have a central effect on this increased risk, it is still debated whether other non-estrogenic mechanisms are related, since hormone replacement alone does not reduce cardiovascular events. Sirtuins and soluble advanced glycation product receptors (sRAGE) are associated with increased vascular protection, while the role of apoptosis inhibiting proteins, a pathway linked to increased cancer incidence, is still unclear in the context of atherosclerosis. Resveratrol is a key activator of sirtuins and potentially modulates these metabolic pathways, reducing cardiovascular risk. This randomized, double-blind, parallel, placebo-controlled clinical trial will be carried out in 80 postmenopausal women with CAD to analyze the effect of treatment with resveratrol on serum concentration and gene expression of sirtuins-1 -3, in the serum sRAGE concentration and in the gene expression of apoptosis inhibitory proteins.

Detailed description: The objective of the study is to evaluate the influence of sirtuins stimulation by resveratrol on inhibitors of apoptosis proteins gene expression of circulation angiogenic cells of postmenopausal women with stable coronary artery disease.

A randomized, double-blind, parallel, placebo-controlled clinical trial in postmenopausal women with CAD submitted to 90 days of daily resveratrol supplementation days of daily supplementation with 1000 mg of resveratrol. Eighty women aged ≥55 years, with overweight or obesity grade 1 (BMI between 25 and 35 kg/m2) will be selected. The participants will be randomized into two groups, control (CON) and resveratrol (RES). After the screening, the participants will undergo the first clinical and laboratory evaluation including lipid and glucose metabolism, inflammatory biomarkers, serum concentrations and gene expression of sirtuin-1 and sirtuin-3 and soluble receptor of advanced glycation end products, and the gene expression of inhibitors of apoptosis proteins.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women;
* Diagnosed coronary artery disease;
* Stable coronary disease;

Exclusion Criteria:

* hypo or hyperthyroidism,
* rheumatic disease,
* use of alcohol,
* hepatic failure,
* renal failure
* hormone replacement therapy
* use of insulin

Primary outcomes:
measure: Sirtuin-1 and sirtuin-3
timeFrame: 90 days
measure: Inhibitors of apoptosis proteins
timeFrame: 90 days
measure: sRAGE
timeFrame: 90 days
Secondary outcomes:
measure: Inflammation
timeFrame: 90 days
measure: Cardiometabolic risk factors
timeFrame: 90 days
measure: Anthropometric measures
timeFrame: 90 days
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: INCOR- Heart Institute
state: São Paulo
Study officials:
affiliation: InCor Heart Institute
name: Antonio P Mansur, PhD
role: PRINCIPAL_INVESTIGATOR
References: