Effects of Low-Dose Theophylline During Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

Study Overview
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Brief Summary
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Molecular mechanisms of COPD exacerbations and the modulating effect of low dose theophylline on that inflammation are elucidated in this project. NF-kappa B-dependent pathway and acetylation status of nuclear histones are to be studied.Design: controlled, prospective and randomized study with or without theophylline, a potent HDAC activator.Objectives: 1) To determine NF-kB activation, histone deacetylase (HDAC) and histone acetyl-transferase (HAT) activity in sputum macrophages and blood monocytes during an episode of exacerbation and 3 months later, once stability is achieved. To correlate these measurements with inflammatory and oxidative stress markers and with pulmonary function and clinical variables. 2) To assess the effect of theophylline on previous molecular, functional and clinical data. Method: 25 patients with COPD will be recruited during an episode of exacerbation requiring hospitalization. NF-kB activation, HDAC and HAT activity, markers of inflammation and oxidative stress will be determined with specific assays. These determinations will be repeated once the patient is stable and compared with smokers and non smoker controls with normal lung function

Official Title
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Molecular Mechanisms of COPD Exacerbations. Effect of Low-Dose Theophylline

Conditions
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COPD

Intervention / Treatment
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* Drug: Theophylline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe COPD according to GOLD guidelines Age between 40 and 75 Admission to hospital due to COPD exacerbation Exclusion Criteria: History of asthma Pulmonary embolism Pneumonia Other chronic inflammatory disease Patient on theophylline at the time of admission Patient on oral steroids at the time of admission

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Low-dose theophylline on top of standard therapy for COPD exacerbation | Drug: Theophylline<br>* Theophylline 100 mg bid for 3 months<br>|
| No Intervention: 2<br>Standard therapy for COPD exacerbation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HDAC activity in alveolar macrophages |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung function |  | 3 months | 
| Inflammatory cytokine release in sputum and serum |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD exacerbation, histone, steroid resistance, inflammation, theophylline