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

NCT03774238 | Terminated

• 2 other identifiers: RECHMPL18_04392018-A02886-49
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 2

Brief Summary

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, …)

Conditions

COPD Patients; Healthy

Keywords

Flow-mediated dilatation; COPD; Pulmonary Rehabilitation; Comorbidities; endothelial cell; oxidative stress

Outcome Measures

Primary Outcomes (1)

• Measure of Flow-Mediated Dilatation (FMD)

  Measure of FMD by EndoPAT2000©

  post exercise and after 4 +/- 2 weeks of training

Secondary Outcomes (11)

• Measure of biological vascular markers

  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

  post exercise and after 4 +/- 2 weeks of training

• Vascular function parameters

  after 4 +/- 2 weeks of training

• Vascular function parameters

  after 4 +/- 2 weeks of training

Study Arms (2)

COPD patients

EXPERIMENTAL

FMD analysis Endothelial progenitors Exercise test Exercise training

Other: FMD analysis

Healthy subject

EXPERIMENTAL

FMD analysis Endothelial progenitors Exercise test

Other: FMD analysis

Interventions

FMD analysis OTHER

Blood sample and vascular exploration.

COPD patients; Healthy subject

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Unstabilized comorbidity
• 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

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• University Hospital, Paris: collaborator

Study Sites (2)

CHU Montpellier and CHU Nimes

Montpellier, 34295, France

Location

University Hospital, Paris

Paris, 75015, France

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Fares Gouzi, MD, PhD

  UH Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: COPD patient group (n=50) and Healthy control Group (n=24)
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: December 12, 2018
• Study Start: February 20, 2019
• Primary Completion: November 20, 2024
• Study Completion: November 20, 2024
• Last Updated: September 30, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)