Improving Cardiovascular Health in Patients With Chronic Obstructive Pulmonary Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Other: Placebo; Drug: Resveratrol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Paula Rodriguez Miguelez, PhD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): August 30, 2022
• Study Completion (Actual): August 30, 2023

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Chronic Disease; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: HM20014536

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No