Pathogenetic Mechanisms of Chronic Obstructive Pulmonary Diseases

NCT ID: NCT01378039

Last Updated: 2012-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-30
• Study Completion Date: 2009-06-30

Brief Summary

Asthma and chronic obstructive pulmonary disease(COPD) are common diseases, which tend to even increase in many countries. Both from a clinical and a pathophysiological point of view, this is an important issue. However, an understanding of the relationship between the complex array of cells and mediators involved in asthma and COPD is not yet fully dissected which makes difficult to find a specific and sensitive panel of biomarkers that can reflect intensity of these pathological processes and can help to predict the individual outcome.

Detailed Description

Objectives:

To evaluate the patterns of pathophysiology and genetic predisposition of COPD and asthma

Tasks:

To evaluate patients that respond to corticosteroids and those who do not

Compare the inflammatory markers:

• of COPD and asthma patients before and after treatment with inhaled glucocorticoids
• of COPD and asthma patients that respond to inhaled glucocorticoids and those who do not
• of nonsmokers and smokers asthma patients

To identify a small set of markers that can be used to predict corticosteroid-treatment response in patients with COPD.

To evaluate epigenetic factors

To compare gene mutation and polymorphism between study groups

To evaluate the relationship between genetic predisposition and pathophysiology, clinical symptoms

To evaluate the relationship between patterns of pathophysiology and clinical symptoms, lung function, quality of life in patients with chronic obstructive pulmonary diseases.

Visit 1 Written informed consent will be obtained

• A full medical, surgical, smoking, labour history. A physical examination will be performed
• Resting SaO2 will be measured, exhaled nitric oxide (FENO)
• Chest X-ray
• Patient will fulfil questionnaires
• Spirometry and bronchodilatation test
• Sputum induction and samples will be performed

Visit 2 • Blood samples for blood clotting test and immunological markers will be taken• Cough inhalation challenge

Visit 3

• Patient will be hospitalized to the Department of Pulmonology and Immunology
• Blood samples for genetic analysis will be taken
• Urinary samples will be taken• Methacholine challenge test Polysomnography
• Bronchoscopy (biopsy and BAL)
• Study drug administration

Visit 4 and 5

• Adverse events, COPD or asthma exacerbation, concomitant medications will be recorded, exhaled nitric oxide (FENO)
• Spirometry
• Patient will fulfil questionnaires
• Cough inhalation challenge

Visit 6

• Patient will fulfil questionnaires
• Spirometry and bronchodilatation test.
• Sputum induction and samples will be performed

Visit 7

• Blood samples for blood clotting test, immunological and genetic analysis will be taken• Cough inhalation challenge

Visit 8

• Patient will be hospitalized to the Department of Pulmonology and Immunology
• Urinary samples will be taken• Methacholine challenge test Polysomnography
• Bronchoscopy (biopsy and BAL)
• Further treatment administration

Conditions

COPD; Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: SINGLE

Study Groups

Budesonide

patients who gave their agreement were randomised to 3 months treatment with either inhaled budesonide (400 µg BD) or placebo

Group Type: OTHER

comparison of treatment effect on different markers

Intervention Type: DRUG

inhaled budesonide (400 µg BD) or placebo BD

Interventions

comparison of treatment effect on different markers

inhaled budesonide (400 µg BD) or placebo BD

Intervention Type: DRUG

Other Intervention Names

Budesonide

Eligibility Criteria

Inclusion Criteria

• Male or female outpatients aged 40-80 years inclusive.
• An established clinical history of COPD as defined by the GOLD guidelines.
• COPD patients with a baseline (pre-bronchodilator) FEV1 40-80% of predicted normal value; post-bronchodilator FEV1/FVC ratio ≤ 70% predicted.
• COPD patients with a smoking history (current or ex-smoker) of ≥10 pack years or those who have exposure to occupational dust and chemicals
• An established clinical history of asthma defined by the GINA recommendations.
• Subjects with out hypoxemia (all subjects must have an O2 saturation ≥88% on room air).

Control (healthy) subjects with baseline FEV1 >80% of predicted normal value

• A female is eligible to participate this study if she is of non-childbearing potential, or childbearing potential has a negative pregnancy test.
• Patients who did not use inhaled and oral corticosteroids 6 weeks and/or long acting bronchodilators 4 weeks before study.

Exclusion Criteria

• There is a current respiratory disorder other than COPD and asthma (e.g. lung cancer, sarcoidosis, active tuberculosis etc.)
• Subjects who have had a COPD and asthma exacerbation or respiratory infection in the 4 weeks before Visit 1.
• Subjects with a chest X-ray indicating diagnosis other than COPD or asthma that might interfere with the study.
• Subjects who are unable to stop treatment with inhaled, and oral corticosteroids 6 weeks and/or long acting bronchodilators 4 weeks before study.
• Subjects receiving treatment with cromolyn sodium or nedocromil, oral beta2 - agonists, long acting anticholinergic, leucotriene modifiers
• Subjects who have had lung surgery.
• Subjects with bleeding diathesis.
• Subjects receiving treatment with long-term oxygen therapy.
• Subjects with serious, uncontrolled diseases those are uncontrolled on permitted therapy.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Göteborg University

OTHER

Sponsor Role: collaborator

Lithuanian University of Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Raimundas Sakalauskas

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Raimundas Sakalauskas, Prof.

Role: PRINCIPAL_INVESTIGATOR

Kaunas University of Medicine

References

O'Neil SE, Sitkauskiene B, Babusyte A, Krisiukeniene A, Stravinskaite-Bieksiene K, Sakalauskas R, Sihlbom C, Ekerljung L, Carlsohn E, Lotvall J. Network analysis of quantitative proteomics on asthmatic bronchi: effects of inhaled glucocorticoid treatment. Respir Res. 2011 Sep 22;12(1):124. doi: 10.1186/1465-9921-12-124.

Reference Type: DERIVED

PMID: 21939520 (View on PubMed)

Other Identifiers

48/2004

Identifier Type: -

Identifier Source: org_study_id