Chronic Obstructive Pulmonary DiseaseNCT02220387
Molecular, Cytological Features and Genetic Susceptibility of COPD Attributable to Different Environmental Exposures
An observational study of Chronic Obstructive Pulmonary Disease, run by Novosibirsk City Hospital #2 at 1 site in Russia.
Trial summary
The objective of this study is to investigate molecular, cytological and genetic features of occupational chronic obstructive pulmonary disease (COPD) in conditions of different occupational exposures. Read more about this study
- Who is it for?
- Ages 40 to 75 years, men only
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- exposure to respirable silica dust and exposure to polycyclic aromatic hydrocarbons exhaust
- How many people
- 352 participants
- Where
- 1 siteRussia
- Study dates
- Aug 2014to Sep 2014
- 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 75 years
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Residents of a certain town (Novosibirsk, Russian Federation)
Who may be able to join
- Post- bronchodilator forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio less than 0.7
- Stable phase of COPD
- History of exposure to respirable silica dust, nonsmokers with absence of passive exposure to tobacco smoke or history of exposure to polycyclic aromatic hydrocarbons exhaust, nonsmokers with absence of passive exposure to tobacco smoke or current tobacco smokers without history of occupational exposure
- COPD risk factor exposure (occupational or tobacco smoke) duration not less than 12 months
- Male
- Caucasian
- Age of 40 - 75 years old
- Control group - healthy people
Who cannot join
- history of biomass smoke exposure
- age less than 40 and above 75 years old
- current COPD exacerbation
- concomitant asthma
- tuberculosis and other pulmonary diseases
- allergic and autoimmune disorders
Show all 11Show fewer
- active infections
- immunodeficiency, including HIV infection
- parasitological diseases
- malignancies
- lack of informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Molecular, Cytological Features and Genetic Susceptibility of Occupational Chronic Obstructive Pulmonary Disease Attributable to Different Environmental Exposures
The objective of this study is to investigate molecular, cytological and genetic features of occupational chronic obstructive pulmonary disease (COPD) in conditions of different occupational exposures. In order to achieve this goal serum pro-inflammatory cytokines and standard inflammation markers level, hemostasis, cytological analysis of bronchoalveolar lavage and associations of single nucleotide polymorphisms (SNPs) rs1800470 transforming growing factor β1 (TGF β1) gene, rs1828591 hedgehog interacting protein (HHIP) gene, rs4129267 interleukin 6 receptor (IL-6R) gene, rs1051730 nicotinic acetylcholine receptor 3 (CHRNA3) gene with COPD in subjects exposed to silica dust and in those exposed to polycyclic aromatic hydrocarbons exhaust will be investigated. The relationship between genotype and phenotype characteristics, such as an inflammation activity, assessed by C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF α) serum concentration, in different occupational COPD groups will be studied. The hypothesis is that the mechanisms underlying disease development and progression are different due to environmental risk factor that reflex in differs in disease attributes - molecular biomarkers, cytology results and genetic susceptibility between COPD due to dust, COPD due to chemicals and COPD in smokers therefore COPD can be subdivided into ecological phenotypes according to environmental risk factor.
Read the detailed description
Study rationale: The main risk factors of COPD are tobacco smoking, biomass smoking and occupational factors. Tobacco smoking is well-known risk factor so tobacco induced COPD is completely established. Nevertheless the meaning of occupational factors which are less famous are equally important. Based on comprehensive literature review American Thoracic Society (ATS) endorsed the notion that strong evidence implicates occupational factors as cause of COPD [Eisner MD et al., 2010]. Occupational COPD takes 19.2 % of all COPD patients and 31.1 % of never smokers as resulted NHANESIII study [Hnizdo E. et al., 2004]. A considerable number of work-related factors have evidence for a causal association with COPD including (and of course not limited) silica and silicates and polycyclic aromatic hydrocarbons. Individuals in a variety of occupations and industries such as coal miners, coke workers, tunnel workers, metallurgists, welding workers, transportation workers, builders, farmers are exposed to factors cited above. Despite this the clinical and pathophysiological features of COPD caused by occupational factors are still unclear.
Occupational factors leading airflow limitation are various entities - vapors, dusts, gases and fumes with different physical, chemical, biological and other features, so the mechanisms underlying disease development and progression may be different attributable to risk factor.
An environmental risk factors exposure as well as tobacco smoking results in COPD only in part of the subjects which indicates the significant genome and gene environmental interactions role. COPD develops in predisposed subjects undergoing risk factors exposure. Therefore the risk of COPD is individual and depends on both genetic and environments. There are few data concerning the effects of genetic on COPD risk in this specific subgroup - people who are exposed to occupational risk factors related to the certain environmental factor.
Statistical analysis: Statistical analysis will be carried out by Statistica 9.0 software. Significance level will be considered p = 0.05. The qualitative variables will be expressed as counts and percentages. The quantitative continuous variables will be expressed as means and standard error of means (M ± m) for variables that meet the criteria of normality and minimum and maximum, median for those that do not meet the criteria of normality. Kruskal-Wallis test will be used for comparing multiply independent samples and Mann-Whitney U test for comparing two independent samples if variable under consideration will continuous and that it will be measured on an ordinal scale. For comparisons of proportions, the Chi-square will be used.
For associations assessment logistic regression method will be used. The odds ratio (OR) and 95% confidence interval (CI) will be calculated for each professional group. Multiple regression model will be used to explore the relationships between demographic characteristics, cytokine concentrations, hemostasis and airflow limitation in professional groups.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- exposure to respirable silica dust, exposure to polycyclic aromatic hydrocarbons exhaust
- Keywords
- occupational COPD, phenotype, genetic
- 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.
exposure to respirable silica dustOther
History of exposure to respirable silica dust due to job
exposure to polycyclic aromatic hydrocarbons exhaustOther
history of exposure to polycyclic aromatic hydrocarbons exhaust due to job
| Study group | Role | What they receive |
|---|---|---|
| occupational COPD | Consists of 2 subgroups
1. COPD patients with history of exposure to respirable silica dust
2. COPD patients with history of exposure to polycyclic aromatic hydrocarbons exhaust Receives: Other: exposure to respirable silica dust; Other: exposure to polycyclic aromatic hydrocarbons exhaust | |
| smokers with COPD and healthy control | Consists of 2 subgroups 1. patients with COPD, history of tobacco smoke and no history of occupational exposure 2. healthy subjects |
What is being measured
The primary outcome is the main question the study is designed to answer.
Association of SNPs rs1800470 TGF β1 gene, rs1828591 HHIP gene, rs4129267 IL-6R gene, rs1051730 CHRNA3 gene with COPD in subjects exposed to dust and in those exposed to chemicals.
Odds ratio and 95% confidence interval will be calculated for each occupational group. Controls - healthy people.
Measured: 1 day (a single measurement)
Difference in cytological analysis of bronchoalveolar lavage fluid results between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in serum interleukin 1 beta (IL-1β) level between COPD patients exposed to dust, chemicals and tobacco smoke.
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in serum TNFα level between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in spontaneous thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in collagen induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in epinephrine induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in adenosine diphosphate induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in fibrinogen level between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in fibrinogen degradation products level between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in D-dimer level between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in serum endothelin1 level between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Difference in serum nitric oxide level between COPD patients exposed to dust, chemicals and tobacco smoke
Comparison of groups.
Measured: 1 day (a single measurement)
Secondary outcomes (1)
Relationship between genotype and phenotype characteristics, such as an inflammation activity, assessed by hsCRP and TNF α serum concentration, in different occupational COPD groups.
For SNPs that will occur associated with occupational COPD differences in hsCRP and TNFα serum concentration between subjects with different genotypes will be established separately for exposed to dust COPD group and for exposed to chemicals COPD group.
Measured: 1 day (a single measurement)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2014 (estimated)
- Study startAug 2014
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies 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
- Cross-sectional
- Enrolment
- 352 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novosibirsk City Hospital #2
- Sponsor type
- University, hospital or other
- Collaborators
- Siberian Branch of the Russian Academy of Medical Sciences
- Responsible party
- Principal investigator, Liubov A Shpagina, Novosibirsk City Hospital #2
- Investigators
- Liubov Shpagina, PhD, Principal investigator, Novosibirsk Citi Hospital #2, Novosibirsk State Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02220387
- Sponsor's protocol ID
- 01201463369/1
- Other IDs
- 01201463369
- Status last verified
- Oct 2015
- First submitted
- 11 Aug 2014
- Last updated
- 6 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular, Cytological Features and Genetic Susceptibility of Occupational Chronic Obstructive Pulmonary Disease Attributable to Different Environmental Exposures
- ClinicalTrials.gov ID
- NCT02220387
- Acronym / sponsor ID
- 01201463369/1
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- occupational COPD, phenotype, genetic
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 352 participants (actual)
- Lead sponsor
- Novosibirsk City Hospital #2University, hospital or other
- Collaborators
- Siberian Branch of the Russian Academy of Medical Sciences
- Study start
- Aug 2014
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 19 Aug 2014 (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.
The objective of this study is to investigate molecular, cytological and genetic features of occupational chronic obstructive pulmonary disease (COPD) in conditions of different occupational exposures. In order to achieve this goal serum pro-inflammatory cytokines and standard inflammation markers level, hemostasis, cytological analysis of bronchoalveolar lavage and associations of single nucleotide polymorphisms (SNPs) rs1800470 transforming growing factor β1 (TGF β1) gene, rs1828591 hedgehog interacting protein (HHIP) gene, rs4129267 interleukin 6 receptor (IL-6R) gene, rs1051730 nicotinic acetylcholine receptor 3 (CHRNA3) gene with COPD in subjects exposed to silica dust and in those exposed to polycyclic aromatic hydrocarbons exhaust will be investigated. The relationship between genotype and phenotype characteristics, such as an inflammation activity, assessed by C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF α) serum concentration, in different occupational COPD groups will be studied. The hypothesis is that the mechanisms underlying disease development and progression are different due to environmental risk factor that reflex in differs in disease attributes - molecular biomarkers, cytology results and genetic susceptibility between COPD due to dust, COPD due to chemicals and COPD in smokers therefore COPD can be subdivided into ecological phenotypes according to environmental risk factor.
Detailed description
Study rationale: The main risk factors of COPD are tobacco smoking, biomass smoking and occupational factors. Tobacco smoking is well-known risk factor so tobacco induced COPD is completely established. Nevertheless the meaning of occupational factors which are less famous are equally important. Based on comprehensive literature review American Thoracic Society (ATS) endorsed the notion that strong evidence implicates occupational factors as cause of COPD [Eisner MD et al., 2010]. Occupational COPD takes 19.2 % of all COPD patients and 31.1 % of never smokers as resulted NHANESIII study [Hnizdo E. et al., 2004]. A considerable number of work-related factors have evidence for a causal association with COPD including (and of course not limited) silica and silicates and polycyclic aromatic hydrocarbons. Individuals in a variety of occupations and industries such as coal miners, coke workers, tunnel workers, metallurgists, welding workers, transportation workers, builders, farmers are exposed to factors cited above. Despite this the clinical and pathophysiological features of COPD caused by occupational factors are still unclear.
Occupational factors leading airflow limitation are various entities - vapors, dusts, gases and fumes with different physical, chemical, biological and other features, so the mechanisms underlying disease development and progression may be different attributable to risk factor.
An environmental risk factors exposure as well as tobacco smoking results in COPD only in part of the subjects which indicates the significant genome and gene environmental interactions role. COPD develops in predisposed subjects undergoing risk factors exposure. Therefore the risk of COPD is individual and depends on both genetic and environments. There are few data concerning the effects of genetic on COPD risk in this specific subgroup - people who are exposed to occupational risk factors related to the certain environmental factor.
Statistical analysis: Statistical analysis will be carried out by Statistica 9.0 software. Significance level will be considered p = 0.05. The qualitative variables will be expressed as counts and percentages. The quantitative continuous variables will be expressed as means and standard error of means (M ± m) for variables that meet the criteria of normality and minimum and maximum, median for those that do not meet the criteria of normality. Kruskal-Wallis test will be used for comparing multiply independent samples and Mann-Whitney U test for comparing two independent samples if variable under consideration will continuous and that it will be measured on an ordinal scale. For comparisons of proportions, the Chi-square will be used.
For associations assessment logistic regression method will be used. The odds ratio (OR) and 95% confidence interval (CI) will be calculated for each professional group. Multiple regression model will be used to explore the relationships between demographic characteristics, cytokine concentrations, hemostasis and airflow limitation in professional groups.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| occupational COPD | – | Other: exposure to respirable silica dust, Other: exposure to polycyclic aromatic hydrocarbons exhaustConsists of 2 subgroups 1. COPD patients with history of exposure to respirable silica dust 2. COPD patients with history of exposure to polycyclic aromatic hydrocarbons exhaust |
| smokers with COPD and healthy control | – | –Consists of 2 subgroups 1. patients with COPD, history of tobacco smoke and no history of occupational exposure 2. healthy subjects |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Residents of a certain town (Novosibirsk, Russian Federation)
Key inclusion criteria (8 listed)
- Post- bronchodilator forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio less than 0.7
- Stable phase of COPD
- History of exposure to respirable silica dust, nonsmokers with absence of passive exposure to tobacco smoke or history of exposure to polycyclic aromatic hydrocarbons exhaust, nonsmokers with absence of passive exposure to tobacco smoke or current tobacco smokers without history of occupational exposure
- COPD risk factor exposure (occupational or tobacco smoke) duration not less than 12 months
- Male
Key exclusion criteria (11 listed)
- history of biomass smoke exposure
- age less than 40 and above 75 years old
- current COPD exacerbation
- concomitant asthma
- tuberculosis and other pulmonary diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| exposure to respirable silica dustHistory of exposure to respirable silica dust due to job | Other | occupational COPD |
| exposure to polycyclic aromatic hydrocarbons exhausthistory of exposure to polycyclic aromatic hydrocarbons exhaust due to job | Other | occupational COPD |
Primary outcome
Association of SNPs rs1800470 TGF β1 gene, rs1828591 HHIP gene, rs4129267 IL-6R gene, rs1051730 CHRNA3 gene with COPD in subjects exposed to dust and in those exposed to chemicals.
Time frame: 1 day (a single measurement)
Odds ratio and 95% confidence interval will be calculated for each occupational group. Controls - healthy people.
Difference in cytological analysis of bronchoalveolar lavage fluid results between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in serum interleukin 1 beta (IL-1β) level between COPD patients exposed to dust, chemicals and tobacco smoke.
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in serum TNFα level between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in spontaneous thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in collagen induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in epinephrine induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in adenosine diphosphate induced thrombocyte aggregation between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in fibrinogen level between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in fibrinogen degradation products level between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in D-dimer level between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in serum endothelin1 level between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
Difference in serum nitric oxide level between COPD patients exposed to dust, chemicals and tobacco smoke
Time frame: 1 day (a single measurement)
Comparison of groups.
1 secondary outcome
Relationship between genotype and phenotype characteristics, such as an inflammation activity, assessed by hsCRP and TNF α serum concentration, in different occupational COPD groups.
Time frame: 1 day (a single measurement)
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 6 Oct 2015.
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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.
Liubov Shpagina, PhD principal investigator
Novosibirsk Citi Hospital #2, Novosibirsk State Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Obstructive Pulmonary Disease, run by Novosibirsk City Hospital #2 at 1 site in Russia.
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 8 inclusion and 11 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 6 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. 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?
Association of SNPs rs1800470 TGF β1 gene, rs1828591 HHIP gene, rs4129267 IL-6R gene, rs1051730 CHRNA3 gene with COPD in subjects exposed to dust and in those exposed to chemicals. (time frame: 1 day (a single measurement)). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Oct 2015.