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Integrative-omics of the Disordered COPD Small Airway Epithelium

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ClinicalTrials.gov Identifier: NCT02183818
Recruitment Status : Recruiting
First Posted : July 8, 2014
Last Update Posted : May 1, 2018
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:
We aim to use an integrated network systems approach to analyze certain existing small airway epithelium (SAE) omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomic levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease.

Condition or disease
Smoking COPD

Detailed Description:

Hypothesis: We hypothesize that the disordered differentiation of the SAE that characterizes COPD results from the complex interaction of cigarette smoke components with a hierarchy of genetic, epigenetic, gene expression and metabolomics network interactions as the BC differentiate into a mucociliary epithelium.

Specific aim 1. Using an integrated network systems approach to analyze our extensive existing SAE omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomics levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease.

Specific aim 2. To refine the model, a comprehensive omics data set will be collected at multiple time points as SAE BC of nonsmokers and COPD smokers differentiate to normal and disordered mucociliary epithelium (respectively) on air-liquid interface (ALI) culture, an in vitro model of SAE differentiation. The computational strategies from aim 1 will be used to improve the model with these data.

Specific aim 3. To test and finalize the integrated network model, a parallel omics data set will be generated from BC from nonsmokers, and COPD smokers as they differentiate on ALI under conditions where key hubs will be up- or down-regulated and the differentiation process stressed under conditions mimicking the in vivo SAE environment. The end result will be an integrated systems model of SAE biology and how this is disordered in COPD.


Study Type : Observational
Estimated Enrollment : 717 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Integrative-omics of the Disordered COPD Small Airway Epithelium
Study Start Date : April 2013
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2021

Group/Cohort
Healthy nonsmokers
Physical assessment, EKG, blood and urine draw, chest x-ray, pulmonary function test (PFT), and bronchoscopy
Smokers with COPD
Physical assessment, EKG, blood and urine draw, chest x-ray, pulmonary function test (PFT), and bronchoscopy



Primary Outcome Measures :
  1. Identification of network pressure points relevant to SAE biology confirmed by analyze of SAE data sets. [ Time Frame: One Year ]
    Using an integrated network systems approach to analyze our extensive existing SAE omic data sets at the genetic, epigenetic (methylation), gene expression, microRNA and metabolomics levels, to develop an initial model of network connectivities and key network pressure points relevant to SAE biology in health and disease.



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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
New York Metropolitan Area residents
Criteria

Healthy nonsmokers (n=50)

Inclusion criteria

  • Must be enrolled into IRB approved protocol #1204012331(all inclusion criteria from protocol #1204012331 thus applies to this protocol)
  • Self-reported never-smokers, with current smoking status validated by the absence of nicotine metabolites in urine (nicotine less than 2 ng/ml and cotinine less than 5 ng/ml)
  • Negative HIV serology

Smokers with COPD (n=50)

Inclusion criteria

  • Must be enrolled into IRB approved protocol #1204012331(all inclusion criteria from protocol #1204012331 thus applies to this protocol)
  • Self-reported current daily smokers with greater than or equal to 10 pack-yr, validated by any of the following: urine nicotine greater than 30 ng/ml or urine cotinine greater than 50 ng/ml
  • Meeting GOLD stages I-III criteria for chronic obstructive lung disease (COPD) based on postbronchodilator spirometry
  • Taking any or no pulmonary-related medication, including beta-agonists, anticholinergics, or inhaled corticosteroids
  • Negative HIV serology

Healthy nonsmokers (n=50)

Exclusion criteria

  • Unable to meet the inclusion criteria (all exclusion criteria from protocol #1204012331 applies to this protocol)
  • Evidence of malignancy within the past 5 years

Smokers with COPD (n=50)

Exclusion criteria

  • Unable to meet the inclusion criteria (all exclusion criteria from protocol #1204012331 applies to this protocol)
  • Individuals in whom participation in the study would compromise the normal care and expected progression of their disease
  • Evidence of malignancy within the past 5 years

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02183818


Contacts
Contact: Grace Mammen, BA, CCRP 646-962-2672 gwm2004@med.cornell.edu

Locations
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Contact: Grace Mammen, BA, CCRP    646-962-2672    gwm2004@med.cornell.edu   
Principal Investigator: Ronald G Crystal, MD         
Principal Investigator: Jason Mezey, PhD         
Principal Investigator: Steven S Gross, PhD         
Sub-Investigator: O'Beirne Sarah, MD/PhD         
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Principal Investigator: Ronald G Crystal, MD Weill Medical College of Cornell University

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT02183818     History of Changes
Other Study ID Numbers: 1301013416
First Posted: July 8, 2014    Key Record Dates
Last Update Posted: May 1, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Weill Medical College of Cornell University:
Smoking
COPD
Non-Smokers
Smokers