Determinants of the Vascular Response to Training in Chronic Obstructive Pulmonary Disease (COPD) Patients (cDysEndoBPCO)

Biological and Functional Determinants of the Endothelial and Vascular Response to Exercise Training in COPD Patients

Vascular comorbidities constitute a major burden in COPD patients. The atherosclerosis process is preceded by the onset of an endothelial dysfunction (assessed by the flow-mediated dilatation (FMD)), which is a risk factor for later ischemic vascular complications and death. In COPD, this endothelial dysfunction could be explained by intrinsic endothelial cell properties, or the effect of a pathogenic endothelial cell microenvironment (inflammation and/or oxidative stress). Exercise training constitue a powerful stimulus for the endothelial function, and could be mediated by the mobiliaztion and function of endothelial progenitors. While exercise training is an efficient intervention in COPD patients, its vascular effect appear blunted. The endothelial function response to training has appeared heterogeneous in COPD patients, and possibly linked to the endothelial cel lesion. Thus, endothelial function (assessed by the FMD) response to exercise training would be lower in COPD patients with a baseline impairment of the their FMD. In addition, of biological and functional factors could explained the magnitude of the FMD response in COPD patients.The aim of the study are thus :

To compare the FMD change in COPD patients with FMD above (FMD+) and under the median FMD (FMD-) after 4 weeks of exercise training in the whole study population.

To compare between COPD patients FMD+, COPD patients FMD- and healthy "control" subjects, the endothelial inflammation and senescence at baseline and the endothelial progenitor mobilization and function change induced by exercise (maximal exercise test and training).

To compare between COPD patients FMD+, COPD patients FMD- and healthy "control" subjects the effect of the endothelial microenvironment on the cellular pathways regulating the endothelial function in vitro at baseline and changes after exercise training.

To test in COPD patients the association between the magnitude of the FMD changes after training and biological, functional and clinical factors (inflammation oxidative stress markers, endothelial biomarkers, pulmonary impairment and phenotype, cardiovascular risks factors, vascular function, metabolic markers, physical activity level, …)

Study Overview

• Status: Terminated
• Conditions: Healthy; COPD Patients
• Intervention / Treatment: Other: FMD analysis

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • CHU Montpellier and CHU Nimes
  • Paris, France, 75015
    • University Hospital, Paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

A/ COPD patients

• age between 35 and 85 years old
• spirometry showing an FEV1/VC < lower limit of normal
• with an indication for a pulmonary rehabilitation program
• written and informed consent for this study signed by the patient

B/ Healthy subjects

• age between 35 and 85 years old
• no cardiovascular or respiratory disease
• normal spirometry

Exclusion Criteria:

• Unstabilized comorbidity
• Subject in a period of exclusion relative to another protocol
• Major protected by law
• Subject participating in another research protocol
• Subject not affiliated to a social security scheme
• Pregnant or lactating woman
• Patient deprived of freedom by court or administrative order

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COPD patients; FMD analysis Endothelial progenitors Exercise test Exercise training	Other: FMD analysis; Blood sample and vascular exploration.
Experimental: Healthy subject; FMD analysis Endothelial progenitors Exercise test	Other: FMD analysis; Blood sample and vascular exploration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Flow-Mediated Dilatation (FMD)	Measure of FMD by EndoPAT2000©	post exercise and after 4 +/- 2 weeks of training

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of biological vascular markers	E-selectin soluble (sE-sel), endotheline 1 (ET1), facteur von Willebrand (vWF), vascular endothelial growth factor A (VEGF-A), Fms-like tyrosine kinase receptor 1 soluble (sFlt-1), Angiopoietine 1 et 2 (Ang-1 Ang-2)	after 4 +/- 2 weeks of training
Number of colonies and function of Endothelial-Colony Formaing cells (ECFC) in vitro		post exercise and after 4 +/- 2 weeks of training
Number endothelial progenitors	CD34+, CD45+ and KDR + subpopulations by flow cytometry	post exercise and after 4 +/- 2 weeks of training
Vascular function parameters	Systolic pressure index (in AU)	after 4 +/- 2 weeks of training
Vascular function parameters	Intima-media thickness (in mm)	after 4 +/- 2 weeks of training
Vascular function parameters	Pulse-wave velocity (in ms-1)	after 4 +/- 2 weeks of training
Pulse-wave velocity (in ms-1)		after 4 +/- 2 weeks of training
Markers of systemic inflammation	C-Reactive protein (in ng/ml)	after 4 +/- 2 weeks of training
Markers of oxidative stress	Lipid peroxidation (in micromol/L)	after 4 +/- 2 weeks of training
Muscle function parameters	Maximum isometric voluntary contraction (in N.m)	after 4 +/- 2 weeks of training
Exercise capacity and vascular adaptation parameters	Maximal oxygen uptake (VO2max, in mL/kg/min)	after 4 +/- 2 weeks of training

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: University Hospital, Paris
• Investigators: Principal Investigator: Fares Gouzi, MD, PhD, UH Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2019
• Primary Completion (Actual): November 20, 2024
• Study Completion (Actual): November 20, 2024

Study Registration Dates

• First Submitted: October 30, 2018
• First Submitted That Met QC Criteria: December 10, 2018
• First Posted (Actual): December 12, 2018

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: COPD; Pulmonary Rehabilitation; oxidative stress; Comorbidities; Flow-mediated dilatation; endothelial cell
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: RECHMPL18_0439; 2018-A02886-49 (Registry Identifier: ID-RCB)

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No