COPDBmiRCOPDNCT02633280
Biomarkers for Diagnosis and Treatment of COPD
An observational study of COPD, run by University of Catanzaro at 3 sites in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- COPD
- How many people
- 195 participants
- Where
- 3 sitesItaly
- Study dates
- Apr 2016to Oct 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Who may be able to join
- COPD diagnosed according to the GOLD criteria
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Italy3 sites
UCCP
Badolato, Catanzaro, 88100
UCCP
Borgia, Catanzaro, 88100
UCCP
Catanzaro, 88100
About this study
Official title: 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
Read the 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.
- Conditions
- COPD
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Change of miR expression at 6 and 12 months
Change of miR expression in COPD-groups (Groups 1 and 2 ) vs control-Group
Measured: 6 and 12 months
Secondary outcomes (3)
correlation between miRs expression and clinical outcome
correlation between miRs and clinical outcome evaluated through the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) dispnea scale
Measured: 6 and 12 months
correlation between miRs expression and the development of adverse drug reaction
correlation between miRs and clinical outcome evaluated through the Naranjo probability scale
Measured: 6 and 12 months
correlation between miRs expression and inflammatory markers
correlation between miRs expression and plasma levels of ILs, TNF-Alpha, C reactive protein
Measured: 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2015 (estimated)
- Study startApr 2016
- Primary completionApr 2017
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 195 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Catanzaro
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luca Gallelli, University of Catanzaro
- Investigators
- Luca Gallelli, MD, Principal investigator, University of Catanzaro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02633280
- Sponsor's protocol ID
- COPD
- Acronym
- BmiRCOPD
- Status last verified
- Sep 2019
- First submitted
- 27 Nov 2015
- Last updated
- 25 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Garvey C. Recent updates in chronic obstructive pulmonary disease. Postgrad Med. 2016;128(2):231-8. doi: 10.1080/00325481.2016.1118352. Epub 2015 Dec 1.
PubMed 26560514Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. doi: 10.1164/rccm.201204-0596PP. Epub 2012 Aug 9.
PubMed 22878278Barnes PJ. Chronic obstructive pulmonary disease: effects beyond the lungs. PLoS Med. 2010 Mar 16;7(3):e1000220. doi: 10.1371/journal.pmed.1000220.
PubMed 20305715Sarioglu N, Hismiogullari AA, Bilen C, Erel F. Is the COPD assessment test (CAT) effective in demonstrating the systemic inflammation and other components in COPD? Rev Port Pneumol (2006). 2016 Jan-Feb;22(1):11-7. doi: 10.1016/j.rppnen.2015.08.007. Epub 2015 Oct 31.
PubMed 26534740Stolzenburg LR, Wachtel S, Dang H, Harris A. miR-1343 attenuates pathways of fibrosis by targeting the TGF-beta receptors. Biochem J. 2016 Feb 1;473(3):245-56. doi: 10.1042/BJ20150821. Epub 2015 Nov 5.
PubMed 26542979Watt J, Ganapathi P. COPD: Novel therapeutics and management strategies--SMi's 7th Annual Conference (October 19-20, 2015--London, UK). Drugs Today (Barc). 2015 Oct;51(10):613-7. doi: 10.1358/dot.2015.51.10.2409817.
PubMed 26583304Agusti A, Edwards LD, Rennard SI, MacNee W, Tal-Singer R, Miller BE, Vestbo J, Lomas DA, Calverley PM, Wouters E, Crim C, Yates JC, Silverman EK, Coxson HO, Bakke P, Mayer RJ, Celli B; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One. 2012;7(5):e37483. doi: 10.1371/journal.pone.0037483. Epub 2012 May 18.
PubMed 22624038
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Predictive "Molecular Biology Signature" for Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease
- ClinicalTrials.gov ID
- NCT02633280
- Acronym / sponsor ID
- BmiRCOPD / COPD
- Conditions
- COPD
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 195 participants (actual)
- Lead sponsor
- University of CatanzaroUniversity, hospital or other
- Study start
- Apr 2016
- Primary completion
- Apr 2017 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 17 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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) |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (1 listed)
- COPD diagnosed according to the GOLD criteria
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
3 secondary outcomes
correlation between miRs expression and clinical outcome
Time frame: 6 and 12 months
correlation between miRs expression and the development of adverse drug reaction
Time frame: 6 and 12 months
correlation between miRs expression and inflammatory markers
Time frame: 6 and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2019.
- Results publication: PubMed 26560514Garvey C. Recent updates in chronic obstructive pulmonary disease. Postgrad Med. 2016;128(2):231-8. doi: 10.1080/00325481.2016.1118352. Epub 2015 Dec 1.
- Results publication: PubMed 22878278Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. doi: 10.1164/rccm.201204-0596PP. Epub 2012 Aug 9.
- Results publication: PubMed 20305715Barnes PJ. Chronic obstructive pulmonary disease: effects beyond the lungs. PLoS Med. 2010 Mar 16;7(3):e1000220. doi: 10.1371/journal.pmed.1000220.
- Results publication: PubMed 26534740Sarioglu N, Hismiogullari AA, Bilen C, Erel F. Is the COPD assessment test (CAT) effective in demonstrating the systemic inflammation and other components in COPD? Rev Port Pneumol (2006). 2016 Jan-Feb;22(1):11-7. doi: 10.1016/j.rppnen.2015.08.007. Epub 2015 Oct 31.
- Results publication: PubMed 26542979Stolzenburg LR, Wachtel S, Dang H, Harris A. miR-1343 attenuates pathways of fibrosis by targeting the TGF-beta receptors. Biochem J. 2016 Feb 1;473(3):245-56. doi: 10.1042/BJ20150821. Epub 2015 Nov 5.
- Results publication: PubMed 26583304Watt J, Ganapathi P. COPD: Novel therapeutics and management strategies--SMi's 7th Annual Conference (October 19-20, 2015--London, UK). Drugs Today (Barc). 2015 Oct;51(10):613-7. doi: 10.1358/dot.2015.51.10.2409817.
- Results publication: PubMed 22624038Agusti A, Edwards LD, Rennard SI, MacNee W, Tal-Singer R, Miller BE, Vestbo J, Lomas DA, Calverley PM, Wouters E, Crim C, Yates JC, Silverman EK, Coxson HO, Bakke P, Mayer RJ, Celli B; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One. 2012;7(5):e37483. doi: 10.1371/journal.pone.0037483. Epub 2012 May 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luca Gallelli, MD principal investigator
University of Catanzaro
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COPD, run by University of Catanzaro at 3 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of miR expression at 6 and 12 months (time frame: 6 and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02633280, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2019.