Biomarkers for Diagnosis and Treatment of COPD (BmiRCOPD)

September 24, 2019 updated by: Luca Gallelli, University of Catanzaro

A Predictive "Molecular Biology Signature" for Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease

COPD is an inflammatory disease characterized by enhanced chronic airway and lung inflammatory responses to noxious agents (e.g. smoke, pollutants) and progressive airflow limitation. In COPD patients there is a spillover of peripheral lung inflammation into systemic circulation resulting in increased level of various inflammatory markers such as: IL-1β, IL-6, IL-8, and TNF-α.

Diagnosis, now, is based on clinical evaluation and spirometry test and COPD treatment includes the use of LABA, LAMA and corticosteroids.

To data no plasmatic marker able to identify the stage of COPD and the response to the treatment have been documented . The aim of this study is to evaluate in COPD patients the role of microRNA as predictive biomarker, of the disease in order to have a signature of miRs typically of COPD

Study Overview

Status

Completed

Conditions

Detailed Description

Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory disorder affecting more than 200 million patients worldwide. It is characterized by enhanced chronic airway and lung inflammatory responses to noxious agents (e.g. smoke, pollutants) and progressive airflow limitation.

Both, prevalence and incidence of this disease are continuously increasing, thus the investigators can predict that in 2020 it will be the third important cause of death in the world.

Several immune system cells (e.g. macrophages, eosinophils) and biochemical mediators (e.g. tumor necrosis factor-alpha, transforming growth factor beta, Interleukins and metalloproteases) are involved in its development and in symptom severity.

It has been suggested that in COPD patients there is a spillover of peripheral lung inflammation into systemic circulation resulting in increased level of various inflammatory markers such as: IL-1β, IL-6, IL-8, and TNF-α. Those biomolecules are responsible of various complication associated with COPD such as cardiovascular disease, hypertension and skeletal muscle weakness to name a few. It is worth to note that the increase of systemic inflammatory markers is also responsible of diabetes, obesity and metabolic syndrome development in COPD patients.

Diagnosis, now, is based on clinical evaluation and spirometry test and COPD treatment includes the use of LABA, LAMA and corticosteroids. Therefore, an early diagnosis in order to asses a specific treatment it is mandatory.

Sarioglu et al.,reported that systemic inflammatory markers levels (in plasma) TNFα, IL-6 and C-reactive protein, persist in the stable period in 110 COPD patients and the C-reactive protein levels correlate with the COPD Assessment Test.

However, C-reactive protein is not a specific marker, while to date more appropriate marker(s) could be represented by microRNA (miR) a key class of gene expression regulators, emerging as crucial players in various biological processes such as cellular proliferation and differentiation, development and apoptosis.

In this concern, Stolzenburg et al., documented, in an experimental model of COPD, that miR-1343 reduces the expression of both isoform of TGF-b receptor 1 and 2, directly targeting their 3' UTRs mRNA region, suggesting a role in the improvement of lung fibrosis.

To date, no other data have been performed yet on this topic. In the present project the investigators would like to screen with nCounter GX Human Inflammation Kit a comprehensive number of 249 human genes known to be differentially expressed in inflammation. The gene list represents a broad range of inflammation-related pathways. In parallel miRs screening will be performed (800 in a single reaction tube) using NanoString Technology Platform. This technology is robust and sensitive and today is used for the validation of New Generation Sequence (NGS) data. Our aim is to evaluate in COPD patients the role of miRs as predictive biomarker, of the disease in order to have a signature of miRs typically of COPD. The signature could be used to monitoring the therapeutic application of drugs used in COPD as well as to asses a Prediction COPD Diagnostic test.

The absence of a plasmatic marker able to identify the stage of disease and the response to the treatment leads to COPD exacerbation and progression, this represent, in the real life, a common problem during COPD treatment and is also related with an increase of sanitary health costs. Last year, the European health bill for COPD treatment increased by USD 10 million and the market is thought to increase up to USD 37.7 million by 2030.

Study Type

Observational

Enrollment (Actual)

195

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

  • Italy
      • Catanzaro, Italy, 88100
        • UCCP
    • Catanzaro
      • Badolato, Catanzaro, Italy, 88100
        • UCCP
      • Borgia, Catanzaro, Italy, 88100
        • UCCP

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 to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

An open label, parallel groups study, will be performed after it is approve by the Ethical committee and before the beginning of the study, all participants will be informed about the aim, procedures, risks and benefits of the study and they will provide a written informed consent

Description

Inclusion Criteria:

  • COPD diagnosed according to the GOLD criteria

Exclusion Criteria:

  • allergy to corticosteroids or to bronchodilators
  • neurodegenerative diseases
  • autoimmune diseases
  • inability to use inhalers
  • progressive serious medical conditions (such as cancer, AIDS or end-stage renal disease)
  • infectious diseases

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
COPD-Untreated (Group 1)
In this Group will be enrolled patients of both sex and older than 40-years with COPD stage GOLD 2 and 3 that did not receive COPD treatment in the last 6 months (beta 2 agonists, corticosteroids, anticholinergics).
COPD-uncontrolled (Group 2)
In this Group will be enrolled patients of both sex and older than 40-years with COPD stage GOLD 2 and 3 that receive a COPD treatment (e.g. beta 2 agonists, corticosteroids, anticholinergics) but with a post-bronchodilator FEV1< 80% and an FEV1/FVC < 0.7 or with 1-2 exacerbation/year
Control subjects (Group 3)
In this Group will be enrolled patients of both sex and older than 40 years; (2) will be free from lung disease as determined by a physician; (3) will have a normal spirometry (FEV1> 85% and FEV1/FVC > 0.7)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of miR expression at 6 and 12 months
Time Frame: 6 and 12 months
Change of miR expression in COPD-groups (Groups 1 and 2 ) vs control-Group
6 and 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
correlation between miRs expression and clinical outcome
Time Frame: 6 and 12 months
correlation between miRs and clinical outcome evaluated through the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) dispnea scale
6 and 12 months
correlation between miRs expression and the development of adverse drug reaction
Time Frame: 6 and 12 months
correlation between miRs and clinical outcome evaluated through the Naranjo probability scale
6 and 12 months
correlation between miRs expression and inflammatory markers
Time Frame: 6 and 12 months
correlation between miRs expression and plasma levels of ILs, TNF-Alpha, C reactive protein
6 and 12 months

Collaborators and Investigators

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

Sponsor

University of Catanzaro

Investigators

  • Principal Investigator: Luca Gallelli, MD, University of Catanzaro

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

April 1, 2016

Primary Completion (Actual)

April 1, 2017

Study Completion (Actual)

October 1, 2018

Study Registration Dates

First Submitted

November 27, 2015

First Submitted That Met QC Criteria

December 14, 2015

First Posted (Estimate)

December 17, 2015

Study Record Updates

Last Update Posted (Actual)

September 25, 2019

Last Update Submitted That Met QC Criteria

September 24, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Other Study ID Numbers

  • COPD

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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