Systemic Inflammation in Chronic Obstructive Pulmonary Disease (COPD)

NCT ID: NCT00850863

Last Updated: 2009-02-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

240 participants

Study Classification

OBSERVATIONAL

Study Start Date

2009-02-28

Study Completion Date

2015-01-31

Brief Summary

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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. Recently it has become clear that cigarette smoke-induced inflammation is not only present in the lungs but also in the blood, and that this systemic inflammation has important consequences for the clinical expression of COPD. The investigators hypothesize that healthy individuals who are susceptible to cigarette smoking demonstrate a higher and aberrant systemic 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 study systemic inflammation in individuals who are or are not susceptible to develop COPD.
* To characterize the switch to chronicity of the systemic inflmmatory response in COPD
* To determine whether the type and severity of the systemic inflammation contributes to the clinical outcome of COPD
* To compare between subjects who are or are not susceptible to develop COPD in peripheral blood, the corticosteroid responsiveness in vitro, and to unravel underlying mechanisms.
* 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
* To develop new biological and clinical markers for the early diagnosis and monitoring of COPD
* To define possible mediators involved in the early induction of COPD in susceptible smokers, and to define new drug targets

Detailed Description

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Conditions

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Chronic Obstructive Pulmonary Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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A

20 healthy individuals not susceptible for COPD (age 18-40 years, 0 \< pack years \> 10, FEV1/FVC \>70% , FEV1 \>85% predicted)

No interventions assigned to this group

B

30 healthy individuals susceptible for COPD (age 40-75years, pack years \>20, FEV1/FVC \> 70%, FEV1 \> 85% predicted)

No interventions assigned to this group

C

20 healthy individuals very susceptible for COPD (age 18-40 year, 0 \< pack years \> 10, FEV1/FVC \> 70%, FEV1 \> 85% predicted)and high prevalance of COPD in smoking family members older than 45 years

No interventions assigned to this group

D1

30 COPD patients with GOLD stage I (age 40-75 years, Pack years \> 10, FEV1/FVC ≤ 70%, FEV1 \> 80% predicted)

No interventions assigned to this group

D2

30 COPD patients with GOLD stage II (age 40-75 years, Pack years \> 10, FEV1/FVC ≤ 70%, FEV1 50-80 predicted)

No interventions assigned to this group

D3

30 COPD patients with GOLD stage III (age 40-75 years, Pack years \> 10, FEV1/FVC ≤ 70%, FEV1 30-50% predicted)

No interventions assigned to this group

D4

30 COPD patients with GOLD stage IV (age 40-75 years,Pack years \> 10, FEV1/FVC ≤ 70%, FEV1 30% predicted)

No interventions assigned to this group

E

20 healthy individuels very susceptible for COPD ( Age 18-40 years,0 \< Pack years \> 10, FEV1/FVC \>70%, FEV1 \> 85% predicted, and one of the smoking family members has severe early onset COPD or mild COPD with very low smoke exposure

No interventions assigned to this group

F

30 COPD patients who are highly susceptible (age \> 53 years with Pack years \> 10 , FEV1/FVC ≤ 70% and FEV1 \< 40% predicted) or (age \>18 years with 0 \< pack years \> 5, FEV1/FVC ≤ 70% and FEV1 \< 80% predicted)

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

Age ≥18 and ≤75 years

* Age, pack years, FEV1/FVC and FEV1% predicted must fit in one of the 9 groups of the study population
* Physically and mentally able to undergo the total study protocol
* Written informed consent

Exclusion Criteria

* 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, pulmonary fibrosis, silicosis, hypersensitivity pneumonitis, asthma
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Academisch Ziekenhuis Maastricht

OTHER

Sponsor Role collaborator

University Medical Center Groningen

OTHER

Sponsor Role collaborator

UMC Utrecht

OTHER

Sponsor Role collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Nycomed

INDUSTRY

Sponsor Role collaborator

Top Institute Pharma

OTHER

Sponsor Role lead

Responsible Party

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University Medical Center Utrecht

Principal Investigators

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Jan-Willem Lammers, Dr. Prof. MD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Locations

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University Medical Center Utrecht

Utrecht, Utrecht, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Leo Koenderman, Dr. Prof.

Role: CONTACT

+31 88 7557255

Facility Contacts

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Leo Koenderman, Dr. Prof

Role: primary

+31 88 7557255

References

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Hoonhorst 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.

Reference Type DERIVED
PMID: 27117828 (View on PubMed)

Hoonhorst 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.

Reference Type DERIVED
PMID: 24622644 (View on PubMed)

Lo 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.

Reference Type DERIVED
PMID: 23377993 (View on PubMed)

Other Identifiers

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23437

Identifier Type: -

Identifier Source: org_study_id

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