Responses Induced by Smoking in Individuals Being Susceptible and Non-Susceptible for Development of COPD

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2008 by Top Institute Pharma
Sponsor:
Collaborators:
University Medical Centre Groningen
UMC Utrecht
GlaxoSmithKline
Nycomed
Information provided by:
Top Institute Pharma
ClinicalTrials.gov Identifier:
NCT00807469
First received: December 11, 2008
Last updated: NA
Last verified: December 2008
History: No changes posted

December 11, 2008
December 11, 2008
January 2009
January 2013   (final data collection date for primary outcome measure)
Local inflammation before and after cigarette smoking assessed by exhaled breath condensate, microprobe sampling and bronchial biopsies. [ Time Frame: n.a. ] [ Designated as safety issue: No ]
Same as current
No Changes Posted
  • 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. [ Time Frame: n.a. ] [ Designated as safety issue: No ]
  • Extensive clinical characterisation including life style factors, lung function, CT scanning of the lung. [ Time Frame: n.a. ] [ Designated as safety issue: No ]
  • Distribution of candidate genes (SNPs) for COPD within the study population and associations with the inflammatory responses on acute smoking [ Time Frame: n.a. ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Responses Induced by Smoking in Individuals Being Susceptible and Non-Susceptible for Development of COPD
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.

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.
Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Blood will be retained to investigate diffences in candidate genes (SNPs) for COPD between the 5 different groups.

Non-Probability Sample

healthy individuals and COPD patients with GOLD stage II. For detailed describtion see studie cohorts.

Chronic Obstructive Pulmonary Disease
Not Provided
  • 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)
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
120
January 2015
January 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

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, 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
Both
18 Years to 75 Years
Yes
Contact: Nick Ten Hacken, MD +3150-3614574 N.H.T.ten.Hacken@int.umcg.nl
Netherlands
 
NCT00807469
23440
Yes
Professor Dr DS Postma, Pulmonary Department UMCG Groningen, Postbus 9700 RB Groningen
Top Institute Pharma
  • University Medical Centre Groningen
  • UMC Utrecht
  • GlaxoSmithKline
  • Nycomed
Principal Investigator: Dirkje Postma, Dr. Prof. MD UMCG
Top Institute Pharma
December 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP