Pathogenetic Mechanisms of Chronic Obstructive Pulmonary Diseases (CAPTA)

Evaluation of Pathogenetic Mechanisms of Chronic Obstructive Pulmonary Diseases

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.

Study Overview

• Status: Completed
• Conditions: Asthma; COPD
• Intervention / Treatment: Drug: comparison of treatment effect on different markers

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

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Budesonide; patients who gave their agreement were randomised to 3 months treatment with either inhaled budesonide (400 µg BD) or placebo	Drug: comparison of treatment effect on different markers; inhaled budesonide (400 µg BD) or placebo BD; Other Names: Budesonide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Lithuanian University of Health Sciences
• Collaborators: Göteborg University
• Investigators: Principal Investigator: Raimundas Sakalauskas, Prof., Kaunas University of Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: May 31, 2011
• First Submitted That Met QC Criteria: June 20, 2011
• First Posted (Estimate): June 22, 2011

Study Record Updates

• Last Update Posted (Estimate): April 12, 2012
• Last Update Submitted That Met QC Criteria: April 11, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Genetics; Asthma; COPD; Pathophysiology; Treatment response; Phenotype
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: 48/2004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No