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

Sponsors and Collaborators:	Top Institute Pharma University Medical Centre Groningen UMC Utrecht GlaxoSmithKline Nycomed
Information provided by:	Top Institute Pharma
ClinicalTrials.gov Identifier:	NCT00807469

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

MedlinePlus related topics: COPD (Chronic Obstructive Pulmonary Disease) Smoking

U.S. FDA Resources

Study Type:	Observational
Study Design:	Case Control, 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)

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

Biospecimen Description:

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

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
Groningen, Netherlands, 9713 GZ

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

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

Keywords provided by Top Institute Pharma:

COPD
smoking
susceptibility
inflammation
genetic

Study placed in the following topic categories:

Smoking
Lung Diseases, Obstructive
Respiratory Tract Diseases
Disease Susceptibility

Lung Diseases
Genetic Predisposition to Disease
Inflammation
Pulmonary Disease, Chronic Obstructive

Additional relevant MeSH terms:

Lung Diseases, Obstructive
Respiratory Tract Diseases
Lung Diseases
Pulmonary Disease, Chronic Obstructive

ClinicalTrials.gov processed this record on May 06, 2009