Chronic Obstructive Pulmonary DiseaseNCT00807469
Responses Induced by Smoking in Individuals Being Susceptible and Non-Susceptible for Development of COPD
An observational study of Chronic Obstructive Pulmonary Disease, run by Top Institute Pharma at 1 site in Netherlands.
Trial summary
COPD is ranked number 3 by the WHO list of important diseases worldwide and is the only disease with increasing mortality. The pathogenesis of cigarette smoke-induced COPD is obscure, therefore more insight is needed to design effective anti-inflammatory agents. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- How many people
- 120 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2009to Jan 2015
- 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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: healthy individuals and COPD patients with GOLD stage II. For detailed describtion see studie cohorts.
Who may be able to join
- Age 18-75 years
- Age, pack years, FEV1/FVC and FEV1% predicted must fit in one of the 5 groups described above.
- Able to stop smoking for 10 days and start smoking 3-4 cigarettes within 1 hour
- Physically and mentally able to undergo the total study protocol
- Written informed consent
Who cannot join
- Participation in another study
- Alpha-1-antitrypsin deficiency
- Selected grade 1-3 co-morbidity listed in the ACE-27
- Active pulmonary infection like tuberculosis, pneumonia, flue, tracheobronchitis
- Active extra-pulmonary infection like hepatitis A-C, cystitis, gastro-enteritis etc
- Pulmonary diseases like sarcoidosis, IPF, silicosis, hypersensitivity pneumonitis
- Life threatening diseases like carcinoma, AIDS (including HIV+), acute leukaemia etc
- Medication that may affect the results of the study: NSAID's, immunosuppressive agents like prednisolon, metotrexate, azathioprine,Acenocoumarol
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Universitair Medisch Centrum Groningen
Groningen, Provincie Groningen, 9713 GZ
Nick ten Hacken, MD, 050-3614574, N.H.T.ten.Hacken@int.umcg.nl
Nick Ten Hacken, MD
About this study
Official title: Acute and Chronic Inflammatory Responses Induced by Smoking in Individuals Being Susceptible and Non-Susceptible for Development of COPD: From Specific Disease Phenotyping Towards Novel Made Therapy (Study 1)
COPD is ranked number 3 by the WHO list of important diseases worldwide and is the only disease with increasing mortality. The pathogenesis of cigarette smoke-induced COPD is obscure, therefore more insight is needed to design effective anti-inflammatory agents. We hypothesize that healthy individuals who are susceptible to smoking demonstrate a higher and aberrant inflammatory response to cigarette smoke. This susceptibility is caused by heterogeneous factors and is associated with various polymorphic genes that interact with each other and with the environment.
Objective:
- To define mediators involved in the early induction of COPD in susceptible smokers (and so to define new drug targets)
- To develop new biological and clinical markers for the early diagnosis and monitoring of COPD
- To compare between susceptible and non-susceptible individuals the corticosteroid responsiveness of bronchial epithelial cells in vitro, and to study the mechanisms of smoking-induced corticosteroid unresponsiveness.
- To study the role of candidate genes that may play a role in the development of fixed airway obstruction, and to identify clues for patient's responsiveness to specific drugs.
Read the detailed description
Primary study parameters/outcome of the study:
- Local inflammation before and after cigarette smoking assessed by exhaled breath condensate, microprobe sampling and bronchial biopsies.
- Systemic inflammation before and after cigarette smoking assessed by the expression of established and newly developed markers on innate immune cells associated with pre-activation.
- Extensive clinical characterisation including life style factors, lung function, CT scanning of the lung.
- Corticosteroid responsiveness of epithelial cells in vitro.
- Distribution of candidate genes (SNPs) for COPD between the 5 different groups ( see description below) and associations with the inflammatory responses on acute smoking.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- COPD, smoking, susceptibility, inflammation, genetic
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Smoking, Disease Susceptibility, Inflammation
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 |
|---|---|---|
| 1 | 20 healthy individuals not susceptible for COPD (age 18-40 years, >0>10 packyears, FEV1/VC >70%, FEV1 >85% predicted) | |
| 2 | 20 healthy individuals susceptible for COPD (age 18-40 years >20 packyears, FEV1/VC >70%, FEV1 >85% predicted) and high prevalence of COPD in smoking family members older than 45 years | |
| 3 | 20 healthy individuals very susceptible for COPD (age 18-40 years, > 0 > 10 packyears, FEV1/VC >70%, FEV1 >85% predicted), and one of the smoking family members has severe early onset COPD or mild COPD with very low smoke exposure | |
| 4 | 30 healthy individuals not susceptible for COPD (age 40-75 years, >20 packyears, FEV1/VC >70%, FEV1 >85% predicted) | |
| 5 | 30 COPD patients with GOLD stage II (age 40-75 years, >10 packyears, FEV1/VC <_70%, FEV1 50-80% predicted) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local inflammation before and after cigarette smoking assessed by exhaled breath condensate, microprobe sampling and bronchial biopsies.
Secondary outcomes (3)
Systemic inflammation before and after cigarette smoking assessed by the expression of established and newly developed markers on innate immune cells associated with pre-activation.
Extensive clinical characterisation including life style factors, lung function, CT scanning of the lung.
Distribution of candidate genes (SNPs) for COPD within the study population and associations with the inflammatory responses on acute smoking
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2008 (estimated)
- Study startJan 2009
- Primary completionJan 2013 (estimated)
- Study completionJan 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- 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
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Top Institute Pharma
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen, UMC Utrecht, GlaxoSmithKline, Nycomed
- Investigators
- Dirkje Postma, Dr. Prof. MD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00807469
- Sponsor's protocol ID
- 23440
- Status last verified
- Dec 2008
- First submitted
- 11 Dec 2008
- Last updated
- 12 Dec 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Boudewijn IM, Faiz A, Steiling K, van der Wiel E, Telenga ED, Hoonhorst SJM, Ten Hacken NHT, Brandsma CA, Kerstjens HAM, Timens W, Heijink IH, Jonker MR, de Bruin HG, Sebastiaan Vroegop J, Pasma HR, Boersma WG, Wielders P, van den Elshout F, Mansour K, Spira A, Lenburg ME, Guryev V, Postma DS, van den Berge M. Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression. Respir Res. 2017 Dec 21;18(1):213. doi: 10.1186/s12931-017-0696-5.
PubMed 29268739Loi ALT, Hoonhorst S, van Aalst C, Langereis J, Kamp V, Sluis-Eising S, Ten Hacken N, Lammers JW, Koenderman L. Proteomic profiling of peripheral blood neutrophils identifies two inflammatory phenotypes in stable COPD patients. Respir Res. 2017 May 22;18(1):100. doi: 10.1186/s12931-017-0586-x.
PubMed 28532454Hoonhorst SJ, Lo Tam Loi AT, Pouwels SD, Faiz A, Telenga ED, van den Berge M, Koenderman L, Lammers JW, Boezen HM, van Oosterhout AJ, Lodewijk ME, Timens W, Postma DS, Ten Hacken NH. Advanced glycation endproducts and their receptor in different body compartments in COPD. Respir Res. 2016 Apr 26;17:46. doi: 10.1186/s12931-016-0363-2.
PubMed 27117828Hoonhorst SJ, Timens W, Koenderman L, Lo Tam Loi AT, Lammers JW, Boezen HM, van Oosterhout AJ, Postma DS, Ten Hacken NH. Increased activation of blood neutrophils after cigarette smoking in young individuals susceptible to COPD. Respir Res. 2014 Oct 10;15(1):121. doi: 10.1186/s12931-014-0121-2.
PubMed 25301367Hoonhorst SJ, ten Hacken NH, Lo Tam Loi AT, Koenderman L, Lammers JW, Telenga ED, Boezen HM, van den Berge M, Postma DS. Lower corticosteroid skin blanching response is associated with severe COPD. PLoS One. 2014 Mar 12;9(3):e91788. doi: 10.1371/journal.pone.0091788. eCollection 2014.
PubMed 24622644Lo Tam Loi AT, Hoonhorst SJ, Franciosi L, Bischoff R, Hoffmann RF, Heijink I, van Oosterhout AJ, Boezen HM, Timens W, Postma DS, Lammers JW, Koenderman L, Ten Hacken NH. Acute and chronic inflammatory responses induced by smoking in individuals susceptible and non-susceptible to development of COPD: from specific disease phenotyping towards novel therapy. Protocol of a cross-sectional study. BMJ Open. 2013 Feb 1;3(2):e002178. doi: 10.1136/bmjopen-2012-002178. Print 2013.
PubMed 23377993
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute and Chronic Inflammatory Responses Induced by Smoking in Individuals Being Susceptible and Non-Susceptible for Development of COPD: From Specific Disease Phenotyping Towards Novel Made Therapy (Study 1)
- ClinicalTrials.gov ID
- NCT00807469
- Acronym / sponsor ID
- 23440
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- COPD, smoking, susceptibility, inflammation, genetic
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Top Institute PharmaUniversity, hospital or other
- Collaborators
- University Medical Center Groningen, UMC Utrecht, GlaxoSmithKline, Nycomed
- Study start
- Jan 2009
- Primary completion
- Jan 2013 (estimated)
- Study completion
- Jan 2015 (estimated)
- First posted
- 12 Dec 2008 (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 ranked number 3 by the WHO list of important diseases worldwide and is the only disease with increasing mortality. The pathogenesis of cigarette smoke-induced COPD is obscure, therefore more insight is needed to design effective anti-inflammatory agents. We hypothesize that healthy individuals who are susceptible to smoking demonstrate a higher and aberrant inflammatory response to cigarette smoke. This susceptibility is caused by heterogeneous factors and is associated with various polymorphic genes that interact with each other and with the environment.
Objective:
- To define mediators involved in the early induction of COPD in susceptible smokers (and so to define new drug targets)
- To develop new biological and clinical markers for the early diagnosis and monitoring of COPD
- To compare between susceptible and non-susceptible individuals the corticosteroid responsiveness of bronchial epithelial cells in vitro, and to study the mechanisms of smoking-induced corticosteroid unresponsiveness.
- To study the role of candidate genes that may play a role in the development of fixed airway obstruction, and to identify clues for patient's responsiveness to specific drugs.
Detailed description
Primary study parameters/outcome of the study:
- Local inflammation before and after cigarette smoking assessed by exhaled breath condensate, microprobe sampling and bronchial biopsies.
- Systemic inflammation before and after cigarette smoking assessed by the expression of established and newly developed markers on innate immune cells associated with pre-activation.
- Extensive clinical characterisation including life style factors, lung function, CT scanning of the lung.
- Corticosteroid responsiveness of epithelial cells in vitro.
- Distribution of candidate genes (SNPs) for COPD between the 5 different groups ( see description below) and associations with the inflammatory responses on acute smoking.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –20 healthy individuals not susceptible for COPD (age 18-40 years, >0>10 packyears, FEV1/VC >70%, FEV1 >85% predicted) |
| 2 | – | –20 healthy individuals susceptible for COPD (age 18-40 years >20 packyears, FEV1/VC >70%, FEV1 >85% predicted) and high prevalence of COPD in smoking family members older than 45 years |
| 3 | – | –20 healthy individuals very susceptible for COPD (age 18-40 years, > 0 > 10 packyears, FEV1/VC >70%, FEV1 >85% predicted), and one of the smoking family members has severe early onset COPD or mild COPD with very low smoke exposure |
| 4 | – | –30 healthy individuals not susceptible for COPD (age 40-75 years, >20 packyears, FEV1/VC >70%, FEV1 >85% predicted) |
| 5 | – | –30 COPD patients with GOLD stage II (age 40-75 years, >10 packyears, FEV1/VC <_70%, FEV1 50-80% predicted) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- healthy individuals and COPD patients with GOLD stage II. For detailed describtion see studie cohorts.
Key inclusion criteria (5 listed)
- Age 18-75 years
- Age, pack years, FEV1/FVC and FEV1% predicted must fit in one of the 5 groups described above.
- Able to stop smoking for 10 days and start smoking 3-4 cigarettes within 1 hour
- Physically and mentally able to undergo the total study protocol
- Written informed consent
Key exclusion criteria (8 listed)
- Participation in another study
- Alpha-1-antitrypsin deficiency
- Selected grade 1-3 co-morbidity listed in the ACE-27
- Active pulmonary infection like tuberculosis, pneumonia, flue, tracheobronchitis
- Active extra-pulmonary infection like hepatitis A-C, cystitis, gastro-enteritis etc
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
Local inflammation before and after cigarette smoking assessed by exhaled breath condensate, microprobe sampling and bronchial biopsies.
3 secondary outcomes
Systemic inflammation before and after cigarette smoking assessed by the expression of established and newly developed markers on innate immune cells associated with pre-activation.
Extensive clinical characterisation including life style factors, lung function, CT scanning of the lung.
Distribution of candidate genes (SNPs) for COPD within the study population and associations with the inflammatory responses on acute smoking
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2008.
- Derived from this study: PubMed 29268739Boudewijn IM, Faiz A, Steiling K, van der Wiel E, Telenga ED, Hoonhorst SJM, Ten Hacken NHT, Brandsma CA, Kerstjens HAM, Timens W, Heijink IH, Jonker MR, de Bruin HG, Sebastiaan Vroegop J, Pasma HR, Boersma WG, Wielders P, van den Elshout F, Mansour K, Spira A, Lenburg ME, Guryev V, Postma DS, van den Berge M. Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression. Respir Res. 2017 Dec 21;18(1):213. doi: 10.1186/s12931-017-0696-5.
- Derived from this study: PubMed 28532454Loi ALT, Hoonhorst S, van Aalst C, Langereis J, Kamp V, Sluis-Eising S, Ten Hacken N, Lammers JW, Koenderman L. Proteomic profiling of peripheral blood neutrophils identifies two inflammatory phenotypes in stable COPD patients. Respir Res. 2017 May 22;18(1):100. doi: 10.1186/s12931-017-0586-x.
- Derived from this study: PubMed 27117828Hoonhorst SJ, Lo Tam Loi AT, Pouwels SD, Faiz A, Telenga ED, van den Berge M, Koenderman L, Lammers JW, Boezen HM, van Oosterhout AJ, Lodewijk ME, Timens W, Postma DS, Ten Hacken NH. Advanced glycation endproducts and their receptor in different body compartments in COPD. Respir Res. 2016 Apr 26;17:46. doi: 10.1186/s12931-016-0363-2.
- Derived from this study: PubMed 25301367Hoonhorst SJ, Timens W, Koenderman L, Lo Tam Loi AT, Lammers JW, Boezen HM, van Oosterhout AJ, Postma DS, Ten Hacken NH. Increased activation of blood neutrophils after cigarette smoking in young individuals susceptible to COPD. Respir Res. 2014 Oct 10;15(1):121. doi: 10.1186/s12931-014-0121-2.
- Derived from this study: PubMed 24622644Hoonhorst SJ, ten Hacken NH, Lo Tam Loi AT, Koenderman L, Lammers JW, Telenga ED, Boezen HM, van den Berge M, Postma DS. Lower corticosteroid skin blanching response is associated with severe COPD. PLoS One. 2014 Mar 12;9(3):e91788. doi: 10.1371/journal.pone.0091788. eCollection 2014.
- Derived from this study: PubMed 23377993Lo Tam Loi AT, Hoonhorst SJ, Franciosi L, Bischoff R, Hoffmann RF, Heijink I, van Oosterhout AJ, Boezen HM, Timens W, Postma DS, Lammers JW, Koenderman L, Ten Hacken NH. Acute and chronic inflammatory responses induced by smoking in individuals susceptible and non-susceptible to development of COPD: from specific disease phenotyping towards novel therapy. Protocol of a cross-sectional study. BMJ Open. 2013 Feb 1;3(2):e002178. doi: 10.1136/bmjopen-2012-002178. Print 2013.
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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.
Dirkje Postma, Dr. Prof. MD principal investigator
University Medical Center Groningen
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 Top Institute Pharma at 1 site in Netherlands.
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 5 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 12 Dec 2008. 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 Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nick Ten Hacken, MD (+3150-3614574, N.H.T.ten.Hacken@int.umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local inflammation before and after cigarette smoking assessed by exhaled breath condensate, microprobe sampling and bronchial biopsies.. 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 NCT00807469, which also lists 6 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 12 Dec 2008.