Improving Cardiovascular Health in Patients With Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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Researchers have found a link between chronic obstructive pulmonary disease (COPD) and heart disease; however, a link is all they have found. Cardiovascular health in COPD is controlled by different mechanisms including vascular health and systemic inflammation. The investigators have collected preliminary data to support that concentrations of Sirtuin 1 (Sirt1), a protein that plays a key role in cardioprotection, may be involved in cardiovascular health in patients with COPD. Resveratrol, an over the counter natural polyphenol found in a variety of food, is a direct activator of Sirt1 and has been used to improve cardiovascular health in different cohorts. The current project is an attempt to expand previous findings and explore the effects of the sub-chronic use of resveratrol in sustaining the improvements in cardiovascular health in COPD.

Detailed Description
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The present study is designed as a double-blind, randomized, cross-over, placebo-controlled protocol. Patients with COPD will receive either resveratrol (500 mg) or placebo for 12 weeks. A comprehensive evaluation of cardiovascular health will be performed. Results will provide novel insights into the mechanistic role that Sirt1 mediates in COPD related vascular dysfunction and systemic inflammation.

Official Title
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Improving Cardiovascular Health in Patients With Chronic Obstructive Pulmonary Disease: a Mechanistic Approach

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Dietary Supplement: Resveratrol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with a clinical diagnosis of COPD known for at least one year will be allowed to participate Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages II to IV Breathing test ratio (FEV1/FVC) <0.7 Amount of exhaled air (FEV1) <80% predicted after bronchodilator Total Lung Capacity (TLC)>80% Matched healthy volunteers without COPD. Exclusion Criteria: FEV1/FVC>0.7 Clinical diagnosis of heart disease, hypertension or diabetes Use of vasoactive medications (nitrates, Beta blockers) Uncontrolled high blood pressure Pulmonary hypertension Fluid in the lungs Sleep apnea Thyroid problems Anemia Raynaud's phenomenon Gastrointestinal bleeding History of coagulopathies History of low platelets Gangrene of the digits Phenylketonuria Pregnant or women attempting to become pregnant In lactation Individuals who may not be able to read or understand the resveratrol label

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Resveratrol<br>500 mg of time released micronized trans-Resveratrol | Dietary Supplement: Resveratrol<br>* Over the counter supplementation<br>|
| Placebo Comparator: Placebo<br>Placebo will be used in the form of an empty white colored soft vegetarian capsule as resveratrol is presented | Other: Placebo<br>* Empty white colored soft vegetarian capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sirt1 concentrations | Circulating concentrations of Sirt1 before and 12 weeks after both resveratrol and placebo | Baseline to 12 weeks | 
| Change in vascular health | Assessment of vascular health through the evaluation of peripheral vascular using the flow-mediated dilation technique before and 12 weeks after both resveratrol and placebo. | Baseline to 12 weeks | 
| Change in Systemic Inflammation | Systemic inflammation will be evaluated through the assessment of interleukin concentrations using enzyme-linked immunosorbent assay before and 12 weeks after both resveratrol and placebo. | Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Nitric Oxide metabolism | Nitric oxide metabolism will be evaluated through Nitric oxide synthase expression using western blot analysis | Baseline to 12 weeks | 
| Change in Inflammatory activation | The inflammatory cascade of the nuclear factor kappa B will be evaluated through assessment of p65 and p50 expression using western blot analysis | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD