Clinical trial NCT00116402: A Pilot Study of the Mechanism of Synergism Between FP and Salmeterol in Preventing COPD Exacerbations
Official title: A Pilot Study of the Mechanism of Synergism Between Fluticasone (FP) and Salmeterol in Preventing Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: COPD
Chronic Obstructive
Pulmonary Disease
Inhaled Corticosteroids
Airway Inflammation
Bronchoscopy
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2005-06-29
Enrollment: 15
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To evaluate blood and airway neutrophil population in COPD patients by examining adhesion and migration in patients with mild to moderate COPD
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Department of Medicine, Pulmonary & Critical Care Section, The University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Imre Noth, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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