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

Phase 1

Completed

• Conditions: Pulmonary Disease, Chronic Obstructive
• Interventions: Drug: fluticasone and salmeterol

• Registration Number: NCT00116402
• Lead Sponsor: University of Chicago

Brief Summary

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

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.

Study Timeline

• Study Start: 2005-01
• Study First Submitted: 2005-06-28
• Study First Submitted QC: 2005-06-28
• Study First Posted: 2005-06-29
• Primary Completion: 2009-09
• Study Completion: 2009-10
• Status Verified: 2014-08
• Last Update Submitted: 2014-08-04
• Last Update Posted: 2014-08-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	fluticasone and salmeterol	will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID
2	fluticasone and salmeterol	salmeterol 50 mcg BID then crossover to combination therapy with fluticasone 220 mcg BID

Primary Outcome Measures

Name	Time	Method
To evaluate blood and airway neutrophil population in COPD patients by examining adhesion and migration in patients with mild to moderate COPD	12 weeks

Trial Locations

Locations (1)

Department of Medicine, Pulmonary & Critical Care Section, The University of Chicago; 🇺🇸 Chicago, Illinois, United States