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Resveratrol in Metabolic Syndrome: Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02219906
Recruitment Status : Completed
First Posted : August 19, 2014
Last Update Posted : April 19, 2019
Sponsor:
Information provided by (Responsible Party):
John Oates, Vanderbilt University

Tracking Information
First Submitted Date  ICMJE August 14, 2014
First Posted Date  ICMJE August 19, 2014
Last Update Posted Date April 19, 2019
Study Start Date  ICMJE May 2014
Actual Primary Completion Date February 7, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2017)
  • Change in parameters of platelet activation [ Time Frame: baseline, 3 weeks after intervention ]
    Measure platelet-monocyte aggregates by flow cytometry
  • Change in parameter for platelet oxidative stress [ Time Frame: Baseline, 3 weeks after intervention ]
    Measure malondialdehyde adducts of platelet proteins
  • Change in parameter for platelet oxidation levels [ Time Frame: Baseline, 3 week after intervention ]
    Measure superoxide production by platelets
  • Serum Thromboxane measurments [ Time Frame: Baseline, 3 weeks after intervention ]
    Measure thromboxane to assess inflammation
Original Primary Outcome Measures  ICMJE
 (submitted: August 15, 2014)
Change in parameters of platelet activation and oxidative stress [ Time Frame: baseline, 3 weeks after intervention ]
We will assess changes in markers of platelet activation before and after resveratrol or placebo:
  1. flow cytometry of markers of platelet activation
  2. malondialdehyde adducts of platelet proteins
  3. nitric oxide and superoxide production by platelets
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2015)
  • Change in oxidative modifications of HDL [ Time Frame: baseline, three weeks after intervention ]
    Measure change in malondialdehyde adducts in HDL proteins
  • Change in plasma oxidative stress [ Time Frame: baselines, three weeks after intervention ]
    Measure change in plasma isoprostanes
Original Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2014)
  • Change in oxidative modifications of HDL [ Time Frame: baseline, three weeks after intervention ]
    We will assess changes in oxidative modifications of HDL proteins in patients with metabolic syndrome before and after resveratrol or placebo intervention: 1) Measure change in malondialdehyde adducts in HDL proteins
  • Change in oxidative stress [ Time Frame: baselines, three weeks after intervention ]
    We will assess changes in oxidative stress before and after intervention: resveratrol or placebo 1) Measure change in plasma isoprostanes
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Resveratrol in Metabolic Syndrome: Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation
Official Title  ICMJE Resveratrol in Metabolic Syndrome: Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation
Brief Summary

Metabolic syndrome is a group of risk factors that increase a patient's likelihood for heart attack, stroke and diabetes. Our research is aimed at understanding whether a drug, resveratrol, commonly found in grapes and red wine, would have any benefit in reducing risk factors in patients that have metabolic syndrome. Despite the use of aspirin and cholesterol reducing medications, patients with metabolic syndrome still often have sticky platelets and dysfunctional lipid profile. This is likely due to inflammation and high oxidative state. In animal studies, this drug has reduced platelet stickiness and reduced oxidative stress. However, the effects of this drug have not been researched in patients with metabolic syndrome.

We are interested in studying whether the benefits of resveratrol described in animal models can be translated to patients with metabolic syndrome who display high markers of oxidative stress. We plan to give a short intervention of drug to patients and then determine if the drug successfully:

  1. Decreases the stickiness of platelets. This is important because sticky platelets are more likely to form clot and contribute to plaque formation.
  2. Reduce the circulating dysfunctional HDL. HDL and its protein and lipid constituents help to inhibit oxidation, inflammation, activation of the blood vessel wall, coagulation, and platelet aggregation. Dysfunctional HDL, as occurs in metabolic syndrome patients, cannot properly protect against atherosclerosis.
Detailed Description

Patients with metabolic syndrome are at increased risk of thrombotic complications, including myocardial infarction and cardiovascular death. A meta-analysis of the studies assessing cardiovascular risk in metabolic syndrome found a pooled relative risk for incident cardiovascular events and death of 1.78. This propensity for thrombotic vascular events is in the context of an increasing prevalence of metabolic syndrome, which in the 2003-2006 NHANES Survey was found in 34% of the US population over the age of 20.

Two important contributors to the development of myocardial infarction and stroke are lipid rich atheromatous plaques and concomitant platelet aggregation in response to the fissuring of these plaques. A growing body of evidence implicates oxidative modification of lipoprotein lipids and apolipoproteins in the genesis of plaques. Platelet hyperactivity and the variable response to antiplatelet therapy are features of the metabolic syndrome. Oxidative modifications of LDL enhance activation of platelets, which themselves are oxidatively stressed. Myeloperoxidase (MPO) initiates lipid peroxidation leading to dysfunctional HDL production. Therefore, the hypotheses for the proposed investigations will address the effects of resveratrol on platelet hyperactivity and HDL protein modifications in patients with metabolic syndrome. Resveratrol, as predicted from its structure, is an electron rich molecule that can reduce free radicals. It has distinctive actions, however, that differ from compounds that are conventionally referred to as "anti-oxidants". It has particular potency as an inhibitor of radical formation by a number of peroxidases that likely participate in the pathophysiology of metabolic syndrome. These include MPO, the peroxidase site of prostaglandin H synthase-1 (PGHS-1; cyclooxygenase-1(COX-1)) and cytochrome c.

We will test the hypothesis that:

  1. resveratrol reduces platelet activation in patients with metabolic syndrome. and
  2. that resveratrol reduces the oxidative modification of HDL proteins in patients with metabolic syndrome.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Metabolic Syndrome
Intervention  ICMJE
  • Dietary Supplement: Resveratrol
    1000mg tid
    Other Name: tid dosing
  • Dietary Supplement: Placebo
    1000mg tid placebo
    Other Name: tid dosing
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo capsule given three times daily X 3 weeks
    Intervention: Dietary Supplement: Placebo
  • Experimental: Resveratrol
    Resveratrol 1 gram three times daily X 3 weeks
    Intervention: Dietary Supplement: Resveratrol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 17, 2019)
41
Original Estimated Enrollment  ICMJE
 (submitted: August 15, 2014)
118
Actual Study Completion Date  ICMJE April 7, 2019
Actual Primary Completion Date February 7, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Metabolic Syndrome

Exclusion Criteria:

  • Evidence of coronary artery disease
  • Indication for use of aspirin for secondary prevention of thrombotic events
  • Use of non-steroidal anti-inflammatory drugs or anti-platelet agents
  • Pregnancy
  • Patients with history of bleeding or gastrointestinal ulcers
  • Patients with major illnesses such as ongoing malignancies, infections, cirrhosis
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02219906
Other Study ID Numbers  ICMJE 130996
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party John Oates, Vanderbilt University
Study Sponsor  ICMJE Vanderbilt University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: John A Oates, MD Vanderbilt University
PRS Account Vanderbilt University Medical Center
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP