Responses Induced by Smoking in Individuals Being Susceptible and Non-Susceptible for Development of COPD
This study is not yet open for participant recruitment.
Verified December 2008 by Top Institute Pharma
Sponsor:
Top Institute Pharma
Collaborators:
University Medical Centre Groningen
UMC Utrecht
GlaxoSmithKline
Nycomed: A Takeda Company
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
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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
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: A Takeda Company
Investigators
| Principal Investigator: | Dirkje Postma, Dr. Prof. MD | UMCG |
More Information
No publications provided
| 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 Respiration Disorders Pulmonary Disease, Chronic Obstructive Smoking |
Lung Diseases, Obstructive Respiratory Tract Diseases Habits |
ClinicalTrials.gov processed this record on June 18, 2013