mRNA and miRNA Airway Inflammatory Markers

July 8, 2021 updated by: Huib A.M. Kerstjens, University Medical Center Groningen

Responsivity and Reproducibility of Messenger and Micro RNA Airway Inflammatory Markers - a Pilot Study

This study investigates cytokine Messenger (mRNA) and microRNA (miRNA) level expression of interleukin (IL) -6, IL-8, IL-17, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 beta and transforming growth factor (TGF)-beta regarding their reproducibility and responsivity in induced sputum and nasal mucosa of patients with chronic obstructive pulmonary disease (COPD) in order to assess their potential as a biomarker outcome measure.

Study Overview

Status

Completed

Conditions

Detailed Description

Rationale:There is an increased interest to identify sensitive airway biomarkers in order to evaluate the potential and efficacy of anti-inflammatory and -remodelling therapeutic interventions. Biomarkers should be easily obtainable, reliable and valid. In COPD, easily obtainable would suggest use of blood, or more directly associated with the airways: sputum or epithelial brushes. Sputum is an obvious opportunity. It has been shown that gene expression changes in the nasal mucosa might be used as suitable surrogate for epithelial cells of the lower airways in patients with airway inflammatory diseases. However, further studies are needed to validate these assumptions. Measurement of messenger RNA, and of micro RNA derived from sputum samples and nasal brushes would fulfil the ease of use required of a biomarker. Messenger RNA would allow for easier quantification in variable dilution samples (sputum). The Groningen Research Institute for Asthma and COPD (GRIAC research group) has experience with sputum and nasal brushes, mRNA and miRNA, but more information is needed on especially reproducibility of the measurements, as well as on responsivity. Both are a prerequisite when designing new intervention trials with such biomarkers.

Therefore, the aim of this study is to investigate cytokine messenger and microRNA level expression of IL-6, IL-8, IL-17, TNF-alpha, MCP-1, MIP-1 beta and TGF-beta regarding their reproducibility and responsivity in induced sputum and nasal mucosa of COPD patients in order to assess their potential as an objective outcome measure.

The primary objectives of this prospective pilot study are the determination of the reproducibility and responsivity of mRNA level expression of IL-6, IL-8, TNF-alpha, MCP-1, MIP-1 beta, ECP and TGF-beta as airway inflammatory markers in induced sputum as well as mRNA and miRNA expression levels of IL-6, IL-8, IL-17, TNF-alpha, MCP-1, MIP-1 beta and TGF-beta as airway inflammatory markers in nasal mucosa. The secondary objective includes the analyses of the measurement characteristics of inflammation cell profiles, LTB4 and protein levels of IL-6, IL-8, TNF-alpha, MCP-1, MIP-1 beta, ECP and TGF-beta.

Twenty COPD patients with an initial COPD exacerbation will be followed for a period of seven weeks for three consecutive visits

The main parameters of induced sputum samples will be mRNA level expression of IL-6, IL-8, TNF-alpha, MCP-1, MIP-1 beta and TGF-beta. The main parameters of nasal mucosa samples will be mRNA and miRNA level expression of IL-6, IL-8, IL-17, TNF-alpha, MCP-1, MIP-1 beta and TGF-beta.

To allow for full perspective on the outcomes, inflammatory cell profiles, Leukotriene B4 (LTB4) and protein levels of IL-6, IL-8, TNF-alpha, MCP-1, MIP-1 beta, eosinophilic cationic protein (ECP) and TGF-beta in sputum will be assessed.

Study Type

Observational

Enrollment (Actual)

21

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

  • Netherlands
      • Groningen, Netherlands
        • University Medical Center; Department of Pulmonary Diseases

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

40 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Twenty COPD patients with an initial COPD exacerbation will be followed for a period of seven weeks for three consecutive visits

Description

Inclusion Criteria:

  • Men/Women age >40 years.
  • Diagnoses of COPD according to criteria of the American Thoracic Society (ATS), a disease state characterized by the presence of chronic airway obstruction due to chronic bronchitis (cough/sputum on most days a week for 3 months in a year for at least two successive years) and/or emphysema
  • Diagnosis of moderate or severe COPD exacerbation (see "Definitions")
  • FEV1 > 0.8 L and ability to produce sputum after hypertonic saline production
  • Post bronchodilator FEV1/Forced Vital Capacity (FVC) ratio <70 % and post bronchodilator FEV1< 80% pred.
  • A smoking history of >10 pack years

Exclusion Criteria:

  • Pneumonia as determined by X-ray
  • > 48 h intake of prednisolon/antibiotics
  • Need for mechanical ventilation (either invasive or non-invasive)
  • Treatment with immune-modulating agents for any disease
  • Experimental interventions for COPD last half year
  • Former/concomitant diagnosis of asthma
  • Any significant other pulmonary disease or disorder
  • Other significant disease or disorder (like alpha-1-antitrypsine deficiency, significant bronchiectasis, cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic (including diagnosed diabetes), malignant, psychiatric, major physical impairment), which, in the opinion of the investigators may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient's ability to participate in the study.
  • Existing pregnancy/ current willingness for becoming pregnant

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of mRNA cytokine expression measured in induced sputum samples
Time Frame: Change of outcome measures will be assessed during one COPD exacerbation phase, after 42 days and after 44-51 days
mRNA level expression of IL-6, IL-8, TNF-alpha, MCP-1, MIP-1 beta and TGF-beta
Change of outcome measures will be assessed during one COPD exacerbation phase, after 42 days and after 44-51 days
Change of miRNA and mRNA cytokine expression measured in nose mucosa samples
Time Frame: Change of outcome measures will be assessed during one COPD exacerbation phase, after 42 days and after 44-51 days
mRNA and miRNA level expression of IL-6, IL-8, IL-17, TNF-alpha, MCP-1, MIP-1 beta and TGF-beta
Change of outcome measures will be assessed during one COPD exacerbation phase, after 42 days and after 44-51 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of inflammatory cell profiles, LTB4 levels and protein cytokine levels measured in induced sputum samples
Time Frame: Change of outcome measures will be assessed during one COPD exacerbation phase, after 42 days and after 44-51 days
Inflammatory cell profiles; LTB4 levels; protein levels of IL-6, IL-8, TNF-alpha, MCP-1, MIP-1 beta, ECP and TGF-beta
Change of outcome measures will be assessed during one COPD exacerbation phase, after 42 days and after 44-51 days

Collaborators and Investigators

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

Sponsor

University Medical Center Groningen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

November 14, 2017

Primary Completion (ACTUAL)

February 27, 2021

Study Completion (ACTUAL)

March 30, 2021

Study Registration Dates

First Submitted

March 6, 2019

First Submitted That Met QC Criteria

April 18, 2019

First Posted (ACTUAL)

April 23, 2019

Study Record Updates

Last Update Posted (ACTUAL)

July 9, 2021

Last Update Submitted That Met QC Criteria

July 8, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Other Study ID Numbers

  • NL 62038.042.17

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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