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
  Purpose

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.

Condition
Chronic Obstructive Pulmonary Disease

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
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)

Resource links provided by NLM:


Further study details as provided by Top Institute Pharma:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Biospecimen Retention:   Samples With DNA

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


Estimated Enrollment: 120
Study Start Date: January 2009
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
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)

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00807469

Contacts
Contact: Nick Ten Hacken, MD +3150-3614574 N.H.T.ten.Hacken@int.umcg.nl

Locations
Netherlands
Universitair Medisch Centrum Groningen Not yet recruiting
Groningen, Netherlands, 9713 GZ
Contact: Nick ten Hacken, MD    050-3614574    N.H.T.ten.Hacken@int.umcg.nl   
Sub-Investigator: Nick Ten Hacken, MD         
Sponsors and Collaborators
Top Institute Pharma
University Medical Centre Groningen
UMC Utrecht
GlaxoSmithKline
Nycomed
Investigators
Principal Investigator: Dirkje Postma, Dr. Prof. MD UMCG
  More Information

No publications provided by Top Institute Pharma

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Professor Dr DS Postma, Pulmonary Department UMCG Groningen, Postbus 9700 RB Groningen
ClinicalTrials.gov Identifier: NCT00807469     History of Changes
Other Study ID Numbers: 23440
Study First Received: December 11, 2008
Last Updated: December 11, 2008
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Top Institute Pharma:
COPD
smoking
susceptibility
inflammation
genetic

Additional relevant MeSH terms:
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 16, 2014