A Pilot Study of the Mechanism of Synergism Between FP and Salmeterol in Preventing COPD Exacerbations

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the blood and airway of subjects with mild to moderate COPD while undergoing standard treatment.

Detailed Description
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Our objective is to examine the mechanism of the additive/synergistic properties of b2-adrenoceptor stimulation and corticosteroid receptor activation in: Preventing neutrophil adhesion to specific endothelial ligands, e.g. ICAM-1 and Undergoing activation as a consequence of this adhesion. We hypothesize that combination therapy with salmeterol + fluticasone (FP) will: Augment the inhibition of adhesion of neutrophils obtained from the peripheral blood of study subjects in vitro, by blocking gIV-PLA2 translocation to the nuclear membrane as for eosinophils; Augment the inhibition of transendothelial migration of neutrophils into airways of subjects with chronic obstructive pulmonary disease; Augment the numbers and concentrations of pro-inflammatory products in the bronchoalveolar lavage fluid; and Decrease the number of neutrophils in the bronchial tissue of endobronchial biopsies of treated patients.

Official Title
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A Pilot Study of the Mechanism of Synergism Between Fluticasone (FP) and Salmeterol in Preventing Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: fluticasone and salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females > 50 years of age Physiologic evidence of COPD defined per ATS guidelines as: cigarette smoking history >20 pack years, FEV1/FVC <70% Patients must have a post-bronchodilator FEV1 >50% of predicted value at enrollment Patient must have an O2 saturation measure by pulse oximetry >90% on RA Must be able to participate in the study, willing to give informed consent, and comply with the study restrictions Exclusion Criteria: Women of child-bearing potential defined as females who are less than 5 years post menopausal unless they have had a hysterectomy or bilateral oophorectomy Observation of any solitary nodule in the lung requiring further medical intervention Patients on maintenance therapy with oral steroids Patients with giant bullous disease Significant other medical conditions, which in the opinion of the investigator, will interfere with the patient's ability to perform the study tests Presence of a coagulopathy as defined by a platelet count <100,000/mm3, and PT and PTT >1.2 x the upper limit of normal Concurrent enrollment or participation in any other clinical trials within the past 30 days Primary diagnosis of asthma History of alpha 1 antitrypsin deficiency Any clinically significant and active pulmonary disease that could contribute to dyspnea Current systemic and inhaled steroids and theophylline

Ages Eligible for Study
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Minimum Age: 50 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID | Drug: fluticasone and salmeterol<br>* will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID will start with salmeterol 50 mcg BID first and then crossover to combination therapy with fluticasone 220 mcg BID.<br>|
| Active Comparator: 2<br>salmeterol 50 mcg BID then crossover to combination therapy with fluticasone 220 mcg BID | Drug: fluticasone and salmeterol<br>* will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID will start with salmeterol 50 mcg BID first and then crossover to combination therapy with fluticasone 220 mcg BID.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate blood and airway neutrophil population in COPD patients by examining adhesion and migration in patients with mild to moderate COPD |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Chronic Obstructive, Pulmonary Disease, Inhaled Corticosteroids, Airway Inflammation, Bronchoscopy