Systemic Inflammation in Chronic Obstructive Pulmonary Disease (COPD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2009 by Top Institute Pharma
Sponsor:
Collaborators:
Academisch Ziekenhuis Maastricht
University Medical Centre Groningen
UMC Utrecht
GlaxoSmithKline
Nycomed
Information provided by:
Top Institute Pharma
ClinicalTrials.gov Identifier:
NCT00850863
First received: February 24, 2009
Last updated: NA
Last verified: February 2009
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. 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

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 Therapy (Study 2).

Resource links provided by NLM:


Further study details as provided by Top Institute Pharma:

Primary Outcome Measures:
  • Systemic inflammation assessed by measurement of expression of established and newly developed markers on innate immune cells; genomic and proteomic analysis of innate immune cells and measurement of pro- and anti-inflammatory cytokines in plasma/serum [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Extensive clinical characterisation of: a) young healthy individuals with low number of pack years who have a high and low familial risk to develop COPD; b) older individuals with higher number of pack years with either a normal lung function or COPD. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Important clinical endpoints include symptoms, lung function, Bode-index, CT-scanning of the lung. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Distribution of candidate genes (SNPs) for COPD between the different groups and relations with systemic inflammation. [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 240
Study Start Date: February 2009
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
A
20 healthy individuals not susceptible for COPD (age 18-40 years, 0 < pack years > 10, FEV1/FVC >70% , FEV1 >85% predicted)
B
30 healthy individuals susceptible for COPD (age 40-75years, pack years >20, FEV1/FVC > 70%, FEV1 > 85% predicted)
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
D1
30 COPD patients with GOLD stage I (age 40-75 years, Pack years > 10, FEV1/FVC ≤ 70%, FEV1 > 80% predicted)
D2
30 COPD patients with GOLD stage II (age 40-75 years, Pack years > 10, FEV1/FVC ≤ 70%, FEV1 50-80 predicted)
D3
30 COPD patients with GOLD stage III (age 40-75 years, Pack years > 10, FEV1/FVC ≤ 70%, FEV1 30-50% predicted)
D4
30 COPD patients with GOLD stage IV (age 40-75 years,Pack years > 10, FEV1/FVC ≤ 70%, FEV1 30% predicted)
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
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)

  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 individuels and COPD patients. For detail description see Groups/Cohorts.

Criteria

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
  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: NCT00850863

Contacts
Contact: Leo Koenderman, Dr. Prof. +31 88 7557255 l.koenderman@umcutrecht.nl

Locations
Netherlands
University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3508GA
Contact: Leo Koenderman, Dr. Prof    +31 88 7557255    l.koenderman@umcutrecht.nl   
Principal Investigator: Jan-Willem Lammers, Dr. Prof. MD         
Sub-Investigator: Leo Koenderman, Dr. Prof.         
Sponsors and Collaborators
Top Institute Pharma
Academisch Ziekenhuis Maastricht
University Medical Centre Groningen
UMC Utrecht
GlaxoSmithKline
Nycomed
Investigators
Principal Investigator: Jan-Willem Lammers, Dr. Prof. MD UMC Utrecht
  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. J-W.J Lammers, University Medical Center Utrecht
ClinicalTrials.gov Identifier: NCT00850863     History of Changes
Other Study ID Numbers: 23437
Study First Received: February 24, 2009
Last Updated: February 24, 2009
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Top Institute Pharma:
COPD
Inflammation
Smoking
Susceptibility

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

ClinicalTrials.gov processed this record on July 31, 2014