ClinicalTrials.gov
ClinicalTrials.gov Menu

Short Interval Resveratrol Trial in Cardiovascular Surgery (SIRT-CVS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03762096
Recruitment Status : Recruiting
First Posted : December 3, 2018
Last Update Posted : December 3, 2018
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Michael Robich, Maine Medical Center

Brief 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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Coronary Artery Disease Dietary Supplement: Trans-resveratrol Dietary Supplement: Placebo Not Applicable

Detailed 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Short Interval Resveratrol Trial in Cardiovascular Surgery
Actual Study Start Date : March 6, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Resveratrol

Arm Intervention/treatment
Experimental: Resveratrol Dietary Supplement: Trans-resveratrol
1 gram, twice a day by mouth Transmax (Biotivia)
Other Name: resveratrol

Placebo Comparator: Placebo Dietary Supplement: Placebo
Placebo




Primary Outcome Measures :
  1. Change in endothelial function [ Time Frame: 6 weeks ]
    Serum levels of nitric oxide (ELISA assay)

  2. Change in endothelial function [ Time Frame: 14 days ]
    Nitric oxide synthase levels in heart tissue (Western blot assay)


Secondary Outcome Measures :
  1. Effects of resveratrol on caveolar function [ Time Frame: 14 days ]
    Lipidomic changes in cell membranes (Mass spectrometry)

  2. Effects of resveratrol on molecular signaling [ Time Frame: 14 days ]
    Serum and tissue levels of pathways associated with glucose metabolism (Western blot assay)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients (age >18 years)
  • Type 2 diabetes (controlled by either oral agents or insulin)
  • Coronary artery disease referred for elective CABG with CPB

Exclusion Criteria:

  • Known decompensated congestive heart failure or systolic heart failure with an ejection fraction < 45% at the time of evaluation
  • Liver Function Tests (LFT) greater than 2 times normal
  • Renal dysfunction (GFR less than 60 mL/min)
  • Abnormal coagulation profile (PT/PTT and INR)
  • Alcohol consumption more than 3 grams (equivalent to 2.5 glasses of wine) daily
  • Positive HIV, Hepatitis B or C testing
  • Severe ventricular arrhythmias
  • Significant hypotension (SBP < 90 mmHg) at the time of enrollment
  • Patients who are pregnant
  • Known malignancy other than non-melanoma skin cancers
  • Expected survival less than one year.
  • Allergy or intolerance to the ingredients of the supplement or the placebo
  • Inability to comply with the study requirements.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03762096


Contacts
Contact: Michael Robich, MD 2077738161 mrobich@mmc.org
Contact: Betsey Gallant 2077738161 BGallant@mmc.org

Locations
United States, Maine
Maine Medical Center Recruiting
Portland, Maine, United States, 04102
Sponsors and Collaborators
Maine Medical Center
American Heart Association

Responsible Party: Michael Robich, Assistant Professor, Surgery, Maine Medical Center
ClinicalTrials.gov Identifier: NCT03762096     History of Changes
Other Study ID Numbers: 1095584
First Posted: December 3, 2018    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Resveratrol
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Enzyme Inhibitors
Platelet Aggregation Inhibitors
Antimutagenic Agents