Integrative-omics of the Disordered COPD Small Airway Epithelium

May 26, 2021 updated by: Weill Medical College of Cornell University
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.

Study Overview

Status

Completed

Conditions

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

Enrollment (Actual)

42

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medical College

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

New York Metropolitan Area residents

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
One Year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Weill Medical College of Cornell University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Boehringer Ingelheim

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 6, 2015

Primary Completion (Actual)

November 17, 2016

Study Completion (Actual)

October 15, 2020

Study Registration Dates

First Submitted

June 17, 2014

First Submitted That Met QC Criteria

July 2, 2014

First Posted (Estimate)

July 8, 2014

Study Record Updates

Last Update Posted (Actual)

May 28, 2021

Last Update Submitted That Met QC Criteria

May 26, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 1301013416
  • R01HL118541 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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