Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03762096 |
| Other study ID # |
1095584 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 6, 2018 |
| Est. completion date |
December 31, 2023 |
Study information
| Verified date |
March 2023 |
| Source |
MaineHealth |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
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.
Description:
Patients with diabetes and metabolic diseases such as obesity, hypertension and dyslipidemia
have a myocardial environment that results in endothelial dysfunction, altered metabolism and
little potential for regeneration by intrinsic or extrinsically delivered therapies. Based
upon work in animal and cell culture models of human disease, caveolae, lipid rafts found on
the cell membrane of endothelial cells and myocytes, are important in cell signaling and
metabolism. A growing body of literature suggests that disruption of membrane lipid
microdomains in diabetes can lead to altered signaling that contributes to cardiovascular
pathology. One possible method to improve the "endothelial health" of the heart could involve
normalizing metabolic processes and decreasing signals that lead to inflammation and pathways
that lead to fibrosis in the myocardium. This presents an opportunity to improve outcomes in
our diabetic patients and improve the success of future therapies aimed at improving
endothelial function.
Resveratrol, a polyphenol found in abundance in red wine, activates sirtuin 1 (SIRT1), an
NAD+-dependent deacetylase, which influences a diverse array of metabolic pathways. Studies
in cultured cells, small animal models, and humans demonstrate that SIRT1 is involved in
endothelial function, mitochondrial biogenesis, insulin production, inflammation, and glucose
and lipid homeostasis. These processes are often dysfunctional in patients with diabetes and
other metabolic diseases.
The central hypothesis of this proposal is that molecular pathology of diabetes on cardiac
endothelium can be corrected with orally supplemented resveratrol.
The investigators propose to test this hypothesis in by first assessing endothelial function,
lipidomic signatures, and cell signaling in patients with and without diabetes mellitus
undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). The
second Aim of this proposal is a pilot placebo-controlled, double-blind clinical trial that
will assess the effects of supplemental resveratrol in diabetic patients undergoing CABG with
CPB. The goal will be to better understand the influence of resveratrol on key molecular
signals that determine endothelial function, calveolar makeup and function, as well as
cytoprotective signaling and responses in the heart.
The Specific Aims of this proposal are to:
Aim 1: Define the molecular pathology of diabetes on cardiac cells and tissues in
non-diabetic and diabetic patients undergoing surgical revascularization. We will assess the
effects of DM on endothelial function and damage, lipidomics, caveolar expression, disrupted
receptor expression and neuregulin signaling.
Aim 2: Determine the effect of resveratrol on the microvascular function of diabetic patients
undergoing surgical revascularization. Through a pilot randomized placebo-controlled clinical
trial, the investigators will evaluate the effect of resveratrol on endothelial damage at the
time of cardiopulmonary bypass, endothelial function, and cell signaling.
This study will further our understanding of how resveratrol impacts patients in a controlled
setting, and will allow for a thorough and complete investigation of how the supplement
affects this patient population clinically and on a molecular level. The data will inform the
development of larger studies examining the benefits of resveratrol in diabetes and metabolic
syndrome. Finally, the investigators successful completion of this trial will inform the
study of other therapeutics where direct myocardial effects are being considered.
