Clinical trial NCT00857038: Doxycycline and Airway Inflammation in Chronic Obstructive Pulmonary Disease (COPD)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Inflammation
Pulmonary Emphysema
Keywords: COPD
Inflammation
Neutrophilic
Myeloperoxidase
Doxycycline
Lead sponsor: Medical Center Alkmaar
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
name: University of Amsterdam
First posted: 2009-03-06
Enrollment: 30
Sex: ALL
Minimum age (years): 41
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: myeloperoxidase in induced sputum
timeFrame: 3 weeks
Secondary outcomes:
measure: MMP-8, MMP-9, IL-6 levels and differential cell counts in induced sputum.
timeFrame: 3 weeks
measure: Lung function (FEV1)
timeFrame: 3 weeks
measure: Symptom scores
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Medical Center Alkmaar
state: Noord-Holland
Study officials:
References:
citation: Prins HJ, Daniels JM, Lindeman JH, Lutter R, Boersma WG. Effects of doxycycline on local and systemic inflammation in stable COPD patients, a randomized clinical trial. Respir Med. 2016 Jan;110:46-52. doi: 10.1016/j.rmed.2015.10.009. Epub 2015 Oct 30.