Pathogenetic Mechanisms of Chronic Obstructive Pulmonary Diseases

Asthma Clinical Trial

— CAPTA  

Official title:

Evaluation of Pathogenetic Mechanisms of Chronic Obstructive Pulmonary Diseases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01378039
• Other study ID #: 48/2004
• Status: Completed
• Phase: N/A
• First received: May 31, 2011
• Last updated: April 11, 2012
• Start date: June 2004
• Est. completion date: June 2009

Study information

• Verified date: April 2012
• Source: Lithuanian University of Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Lithuania: Bioethics Committee
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: June 2009
• Est. primary completion date: December 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator)

Related Conditions & MeSH terms

• Asthma
• COPD
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• comparison of treatment effect on different markers
inhaled budesonide (400 µg BD) or placebo BD

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Lithuanian University of Health Sciences	Göteborg University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in inflammatory cell numbers and inflammatory markers at 3 months	inflammatory cell numbers and inflammatory markers (cytokines, chemokines, etc.) in different tissue compartments (induced sputum, BAL, bronchial biopsies, blood) will be measured at baseline and 3 months after treatment with budesonide and compared with those from healthy subjects	3 months	No
Secondary	network analysis of quantitative proteomics of bronchial biopsies	pathways analysis will be performed on proteins obtained from bronchial biopsies from asthmatics and COPD patients at baseline and 3 months after treatment	3 months	No
Secondary	change of lung function, exNO after 3 months of treatment	lung function measurements (spirometry, bronchial responsiveness measurement, capsaicin test) at baseline and 3 months after treatment with budesonide	3 months	No