Clinical trial NCT01397721: Pulmonary Vascular Changes in Early Chronic Obstructive Pulmonary
Official title: Pulmonary Vascular Changes in Early Chronic Obstructive Pulmonary (MESA-COPD)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Chronic Obstructive Pulmonary Disease (COPD)
pulmonary vasculature
pulmonary hypertension
atherosclerosis
smokers
emphysema
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2011-07-20
Enrollment: 359
Sex: ALL
Minimum age (years): 50
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Approximately Study Subjects:

MESA COPD will recruit approximately 360 participants from EMCAP at Columbia, and from MESA at Columbia; JH University; North Western University; and University of California.

Cases will be defined according to the current American Thoracic Society/European Respiratory Society (ATS/ERS) definition of COPD of a post-bronchodilator capacity (FEV1/FVC) ratio \< 0.70 and classified as mild, moderate and severe as post-bronchodilator FEV1 of 80-100% predicted, 50-80% predicted and \< 50% predicted, respectively.

Controls will be defined in the above sampling frame as those with normal lung function (pre-bronchodilator FEV1/FVC ratio \>= 0.70, and no restrictive ventilatory defect.

Brief summary: The Multi-Ethnic Study of Atherosclerosis (MESA) - Chronic Obstructive Pulmonary Disease (COPD) Study aims to characterize the pulmonary vascular changes and their biology in early COPD using imaging, gene expression profiling and peripheral cellular measures.

Detailed description: Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death in the US and will soon replace stroke as the third leading cause.

Translation of promising biological hypotheses of COPD pathogenesis to human populations that may lead to new therapies is urgently needed. The vascular hypothesis of COPD was articulated almost 50 years ago. Bench research on endothelial dysfunction in COPD is evolving rapidly and has shown that acrolein in cigarette smoke causes endothelial apoptosis and endothelial apoptosis is directly implicated in COPD pathogenesis. Clinical studies on endothelial dysfunction and vascular changes in COPD are limited.

The proposed study is a longitudinal study of smokers nested among the MESA-Lung (AAAA7791) and EMphysema and Cancer Action Project (EMCAP) Studies (AAAA6484), which together provide a well-defined cohort of 4,617 participants with prior spirometry and CT measures.

The Multiethnic Study of Atherosclerosis - Chronic Obstructive Pulmonary Disease (MESA COPD Study) has two main scientific purposes:

1. characterize the pulmonary vascular changes in COPD and their biology, and
2. propose novel pathways for new therapies in COPD.

MESA COPD is a longitudinal study of smokers nested within the MESA-Lung and EMCAP cohorts of 360 participants (160 cases with mild, 60 cases with moderate and 40 cases with severe COPD and 100 controls) who will be phenotyped with magnetic resonance (MR) pulmonary angiography, pulmonary function testing, full-lung CT scans, serum Vascular Endothelial Growth Factor (VEGF), cell assays and gene expression profiling. MESA COPD Study will contribute improving the knowledge of early changes in COPD that may lead to novel disease-modifying medical therapies and preventative strategies.

Eligibility criteria: Inclusion Criteria:

* age 50-79 years at time of enrollment
* ever smokers (10 or more pack-years)
* participation in MESA or EMCAP studies

Exclusion Criteria:

* clinical cardiovascular disease (left congestive heart failure (CHF), valve disease, coronary artery disease (CAD), stroke, or congenital heart disease),
* asthma, pulmonary embolism or lung disease other than COPD,
* weight \> 300 lbs,
* chronic renal insufficiency (\[estimated glomerular filtration rate (eGFR)\] \< 45 mL/min/1.73 m2),
* atrial fibrillation, and
* contraindications to magnetic resonance imagine (MRI), gadolinium, albuterol or spirometry testing.

Primary outcomes:
measure: Change in cardiac structure and pulmonary vascular structure and function
timeFrame: Up to 2 years from start of study
Secondary outcomes:
measure: Number of CD31+/CD42 endothelial microparticles (EMPs)
timeFrame: Up to 2 years from the start of study
measure: Number of circulating endothelial cells (CEC)
timeFrame: Up to 2 years from the start of study
measure: Number of endothelial progenitor cells (EPCs), involved in endothelial repair, are decreased
timeFrame: Up to 2 years from the start of study
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: UCLA Research Center
state: California
city: Chicago
country: United States
facility: Northwestern University Medical School
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: New York
country: United States
facility: Columbia University
state: New York
Study officials:
affiliation: Columbia University
name: R. Graham Barr, MD, DrPh
role: PRINCIPAL_INVESTIGATOR
References: