Integrative-omics of the Disordered COPD Small Airway Epithelium

COPD Clinical Trial

Official title:

Integrative-omics of the Disordered COPD Small Airway Epithelium

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02183818
• Other study ID #: 1301013416
• Secondary ID: R01HL118541
• Status: Completed
• Start date: April 6, 2015
• Est. completion date: October 15, 2020

Study information

• Verified date: May 2021
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: October 15, 2020
• Est. primary completion date: November 17, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• COPD
• Smoking

Locations

Country	Name	City	State
United States	Weill Cornell Medical College	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Boehringer Ingelheim, National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of network pressure points relevant to SAE biology confirmed by analyze of SAE data sets.	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