Doxycycline and Airway Inflammation in Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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COPD is a progressive pulmonary disease that is characterized by an inflammatory process in the airways and the lungs which leads to progressive airway obstruction. The inflammation is associated with tissue loss and remodelling. The investigators hypothesized that doxycycline reduces neutrophilic airway inflammation in patients with COPD. Therefore the investigators will conduct a randomized trial of doxycycline in 30 patients.

Detailed Description
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Rationale: COPD is a disease characterized by chronic inflammation and irreversible airway obstruction. Chronic inflammation lead to degradation of extracellular matrix and hereby destruction of lung parenchyma. Tetracyclines are known for their anti-inflammatory properties in diseases such as rheumatoid arthritis. Objective: To assess the effect of doxycycline on markers of neutrophilic inflammation and proteolytic activity in induced sputum of stable GOLD II and III COPD patients. Study population: Thirty patients with stable GOLD II COPD. Intervention: Placebo versus doxycycline in randomised design.

Official Title
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Doxycycline and Airway Inflammation in COPD: A Randomised Placebo Controlled Trial Studying the Effects of Doxycycline on Airway Inflammation in Patients With Moderate and Severe Stable COPD.

Conditions
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Chronic Obstructive Pulmonary Disease, Inflammation, Pulmonary Emphysema

Intervention / Treatment
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* Drug: Doxycycline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: GOLD II or III COPD (GOLD II: FEV1/FVC < 70%; 50% < FEV1 < 80% predicted, GOLD III: FEV1/FVC < 70%; 30% < FEV1 < 50% predicted ). Stable disease (no exacerbations in the last 3 months). Age > 40 yrs. Written informed consent. Exclusion Criteria: Infections and/or use of antibiotics in the last month. Bacterial colonization of the airways, proven by sputum cultures or broncho-alveolar lavage (BAL). Allergy for tetracyclines or a history of substantial side-effects. Active respiratory diseases other than COPD (e.g. sarcoidosis, tuberculosis, lung cancer, bronchiectasis). Acute exacerbation of COPD as defined by Anthonisen et al. [10]. Signs and/or symptoms of a current respiratory or non-respiratory infection. Use of oral or intravenous corticosteroids or other immunosuppressive drugs within the last month.

Ages Eligible for Study
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Minimum Age: 41 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Doxycycline 100mg daily | Drug: Doxycycline<br>* Doxycycline tablets, 100mg daily<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Placebo tablets 100mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| myeloperoxidase in induced sputum |  | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMP-8, MMP-9, IL-6 levels and differential cell counts in induced sputum. |  | 3 weeks | 
| Lung function (FEV1) |  | 3 weeks | 
| Symptom scores |  | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Inflammation, Neutrophilic, Myeloperoxidase, Doxycycline