The Significance of Circulating Microvesicles in Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (MICROBOPH)

Characterization and Significance of Circulating Microvesicles in Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease

Mild to moderate pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD); such a complication is associated with increased risks of exacerbation and decreased survival. A small proportion of COPD patients may present with severe pulmonary hypertension, defined by a mean pulmonary artery pressure more than 35 mmHg (or more than 20 mmHg with a low cardiac index < 2 l/min/m2) with pulmonary vascular resistance more than 3 Wood units, measured by right heart catheterization (RHC). In these patients, pulmonary microvessels remodeling is the main cause of increase in pulmonary arterial pressure and is thought to result from the combined effects of hypoxia, inflammation, and loss of capillaries but the mechanisms are complex.

For these patients, no drugs have been approved for treatment and lung transplantation must be considered for the more severe patients who are eligible. A better characterization of these patients is needed.

We hypothesize that microvesicles generation and endothelial damage could be related to the severity of pulmonary hypertension due to COPD, assessed by pulmonary hemodynamic parameters. Circulating biomarkers of vascular damage and cell activation will be measured in blood samples from 80 COPD patients who have hemodynamic assessment by RHC. To go further, the origin of the particles will be characterized.

Study Overview

• Status: Not yet recruiting
• Conditions: Obstructive Pulmonary Disease; Pulmonary Hypertension Due to Chronic; Circulating Microvesicles; Circulating Markers of Endothelium Damage
• Intervention / Treatment: Procedure: Catheterization

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: Marianne RIOU; Phone Number: +33 369551145; Email: marianne.riou@chru-strasbourg.fr

Study Locations

• France
  • Strasbourg, France, 67091
    • Hôpitaux Universitaire de Strasbourg - Service Pneumologie - centre de compétence de l'hypertension artérielle pulmonaire - France
    • Contact: Marianne RIOU; Phone Number: + 33 369551145; Email: marianne.riou@chru-strasbourg.fr
    • Principal Investigator: RIOU Marianne
    • Sub-Investigator: KESSLER Romain
    • Sub-Investigator: CANUET Matthieu
    • Sub-Investigator: ENACHE Irina
    • Sub-Investigator: GENY Bernard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with chronic obstructive pulmonary disease, addressed to the competence center PulmoTension of the Strasbourg University hospital, France:

• who are considered for lung transplantation;
• with severe hypoxemia;
• with suspicion of pulmonary hypertension (on echocardiography) And who perform right heart catheterization.

Description

Inclusion criteria:

• Age ≥ 18
• COPD: obstructive ventilatory insufficient on spirometry and history of smoking
• patients who will perform right heart catheterization
• Signature of written informed consent

Exclusion criteria:

• LVEF < 45% (echocardiography)
• Post-capillary pulmonary hypertension (pulmonary capillary wedge pressure > 15 mmHg)
• Chronic Thromboembolic hypertension
• Pulmonary embolism < 6 months
• Acute coronary syndrome < 3 months
• Significant cardiac valvulopathy (echocardiography)
• Portal hypertension
• Connective tissue disease
• chronic renal insufficient (clearance < 40 ml/min)
• Glycated hemoglobin > 7% (if diabetes)
• Non controlled arterial hypertension
• Positive beta-HCG
• Respiratory exacerbation during the inclusive period
• Patients under guardianship or curatorship

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study the rate of circulating endothelial microparticles (EPPs) according to the severity of pulmonary hypertension associated with COPD.	Circulating biomarkers of vascular damage and cell activation will be measured in blood samples from COPD patients who have hemodynamic assessment by RHC. Samples will be withdrawn from occluded pulmonary artery and jugular vein during the exam.	- During the first hemodynamic assessment by RHC; - At 3 to 6 months, if hemodynamic control is required (RHC)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of circulating microvesicles in pulmonary hypertension due to chronic obstructive pulmonary disease	Circulating markers of endothelium damage with circulating microvesicles will be dosed.	- During the first hemodynamic assessment by RHC; - At 3 to 6 months, if an hemodynamic control is required (RHC)
Characterization of circulating microvesicles in pulmonary hypertension due to chronic obstructive pulmonary disease	Proinflammatory markers with circulating microvesicles will be dosed.	- During the first hemodynamic assessment by RHC; - At 3 to 6 months, if an hemodynamic control is required (RHC)
Characterization of circulating microvesicles in pulmonary hypertension due to chronic obstructive pulmonary disease	Cell stimulation estimated with circulating microvesicles will be dosed.	- During the first hemodynamic assessment by RHC; - At 3 to 6 months, if an hemodynamic control is required (RHC)

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France
• Investigators: Principal Investigator: Marianne RIOU, Hôpitaux Universitaires de Strasbourg

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2025

Study Registration Dates

• First Submitted: February 4, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 22, 2022

Study Record Updates

• Last Update Posted (Actual): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 21, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Hypertension; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Hypertension, Pulmonary
• Other Study ID Numbers: 8073

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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