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

Healthy Clinical Trial

— cDysEndoBPCO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03774238
• Other study ID #: UF7699
• Status: Recruiting
• Phase: N/A
• Start date: February 20, 2019
• Est. completion date: May 20, 2024

Study information

• Verified date: August 2023
• Source: University Hospital, Montpellier
• Contact: Fares Gouzi, MD, PhD
• Phone: +33467335908
• Email: f-gouzi[@]chu-montpellier.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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, …)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: May 20, 2024
• Est. primary completion date: November 20, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 35 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• COPD Patients
• Healthy

Intervention

Other:
• FMD analysis
Blood sample and vascular exploration.

Locations

Country	Name	City	State
France	CHU Montpellier and CHU Nimes	Montpellier
France	University Hospital, Paris	Paris

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Montpellier	University Hospital, Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure of Flow-Mediated Dilatation (FMD)	Measure of FMD by EndoPAT2000©	post exercise and after 4 +/- 2 weeks of training
Secondary	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
Secondary	Number of colonies and function of Endothelial-Colony Formaing cells (ECFC) in vitro		post exercise and after 4 +/- 2 weeks of training
Secondary	Number endothelial progenitors	CD34+, CD45+ and KDR + subpopulations by flow cytometry	post exercise and after 4 +/- 2 weeks of training
Secondary	Vascular function parameters	Systolic pressure index (in AU)	after 4 +/- 2 weeks of training
Secondary	Vascular function parameters	Intima-media thickness (in mm)	after 4 +/- 2 weeks of training
Secondary	Vascular function parameters	Pulse-wave velocity (in ms-1)	after 4 +/- 2 weeks of training
Secondary	Pulse-wave velocity (in ms-1)		after 4 +/- 2 weeks of training
Secondary	Markers of systemic inflammation	C-Reactive protein (in ng/ml)	after 4 +/- 2 weeks of training
Secondary	Markers of oxidative stress	Lipid peroxidation (in micromol/L)	after 4 +/- 2 weeks of training
Secondary	Muscle function parameters	Maximum isometric voluntary contraction (in N.m)	after 4 +/- 2 weeks of training
Secondary	Exercise capacity and vascular adaptation parameters	Maximal oxygen uptake (VO2max, in mL/kg/min)	after 4 +/- 2 weeks of training