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

NCT00807469 | Unknown DMC

• 1 other identifier: 23440
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; smoking; susceptibility; inflammation; genetic

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (5)

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)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Top Institute Pharma: lead
• University Medical Center Groningen: collaborator
• UMC Utrecht: collaborator
• GlaxoSmithKline: collaborator
• Nycomed: collaborator

Study Sites (1)

Universitair Medisch Centrum Groningen

Groningen, Provincie Groningen, 9713 GZ, Netherlands

Location

Related Publications (6)

• 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.

  PMID: 29268739 DERIVED

• Loi 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.

  PMID: 28532454 DERIVED

• 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.

  PMID: 27117828 DERIVED

• Hoonhorst 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.

  PMID: 25301367 DERIVED

• 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.

  PMID: 24622644 DERIVED

• 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.

  PMID: 23377993 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

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

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Smoking; Disease Susceptibility; Inflammation

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Study Officials

• Dirkje Postma, Dr. Prof. MD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nick Ten Hacken, MD

CONTACT

+3150-3614574; N.H.T.ten.Hacken@int.umcg.nl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 11, 2008
• First Posted: December 12, 2008
• Study Start: January 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2015
• Last Updated: December 12, 2008

Record last verified: 2008-12

Locations

NL (1)