search
Back to results

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

Primary Purpose

Pulmonary Disease, Chronic Obstructive

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
fluticasone and salmeterol
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive focused on measuring COPD, Chronic Obstructive, Pulmonary Disease, Inhaled Corticosteroids, Airway Inflammation, Bronchoscopy

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Medicine, Pulmonary & Critical Care Section, The University of Chicago

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1

2

Arm Description

will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID

salmeterol 50 mcg BID then crossover to combination therapy with fluticasone 220 mcg BID

Outcomes

Primary Outcome Measures

To evaluate blood and airway neutrophil population in COPD patients by examining adhesion and migration in patients with mild to moderate COPD

Secondary Outcome Measures

Full Information

First Posted
June 28, 2005
Last Updated
August 4, 2014
Sponsor
University of Chicago
Collaborators
GlaxoSmithKline
search

1. Study Identification

Unique Protocol Identification Number
NCT00116402
Brief Title
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

2. Study Status

Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
Collaborators
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
Keywords
COPD, Chronic Obstructive, Pulmonary Disease, Inhaled Corticosteroids, Airway Inflammation, Bronchoscopy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID
Arm Title
2
Arm Type
Active Comparator
Arm Description
salmeterol 50 mcg BID then crossover to combination therapy with fluticasone 220 mcg BID
Intervention Type
Drug
Intervention Name(s)
fluticasone and salmeterol
Intervention Description
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.
Primary Outcome Measure Information:
Title
To evaluate blood and airway neutrophil population in COPD patients by examining adhesion and migration in patients with mild to moderate COPD
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Imre Noth, M.D.
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Medicine, Pulmonary & Critical Care Section, The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
14720023
Citation
Soriano JB, Kiri VA, Pride NB, Vestbo J. Inhaled corticosteroids with/without long-acting beta-agonists reduce the risk of rehospitalization and death in COPD patients. Am J Respir Med. 2003;2(1):67-74. doi: 10.1007/BF03256640.
Results Reference
background
PubMed Identifier
12970006
Citation
Hanania NA, Darken P, Horstman D, Reisner C, Lee B, Davis S, Shah T. The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD. Chest. 2003 Sep;124(3):834-43. doi: 10.1378/chest.124.3.834.
Results Reference
background
PubMed Identifier
12070058
Citation
Hattotuwa KL, Gizycki MJ, Ansari TW, Jeffery PK, Barnes NC. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. Am J Respir Crit Care Med. 2002 Jun 15;165(12):1592-6. doi: 10.1164/rccm.2105025.
Results Reference
background
PubMed Identifier
11118430
Citation
Kim KP, Rafter JD, Bittova L, Han SK, Snitko Y, Munoz NM, Leff AR, Cho W. Mechanism of human group V phospholipase A2 (PLA2)-induced leukotriene biosynthesis in human neutrophils. A potential role of heparan sulfate binding in PLA2 internalization and degradation. J Biol Chem. 2001 Apr 6;276(14):11126-34. doi: 10.1074/jbc.M004604200. Epub 2000 Dec 15.
Results Reference
background
PubMed Identifier
12124392
Citation
Kim YJ, Kim KP, Han SK, Munoz NM, Zhu X, Sano H, Leff AR, Cho W. Group V phospholipase A2 induces leukotriene biosynthesis in human neutrophils through the activation of group IVA phospholipase A2. J Biol Chem. 2002 Sep 27;277(39):36479-88. doi: 10.1074/jbc.M205399200. Epub 2002 Jul 17.
Results Reference
background
PubMed Identifier
14751252
Citation
Chang PS, Absood A, Linderman JJ, Omann GM. Magnetic bead isolation of neutrophil plasma membranes and quantification of membrane-associated guanine nucleotide binding proteins. Anal Biochem. 2004 Feb 15;325(2):175-84. doi: 10.1016/j.ab.2003.10.039.
Results Reference
background
PubMed Identifier
12193740
Citation
Myou S, Zhu X, Boetticher E, Myo S, Meliton A, Lambertino A, Munoz NM, Leff AR. Blockade of focal clustering and active conformation in beta 2-integrin-mediated adhesion of eosinophils to intercellular adhesion molecule-1 caused by transduction of HIV TAT-dominant negative Ras. J Immunol. 2002 Sep 1;169(5):2670-6. doi: 10.4049/jimmunol.169.5.2670.
Results Reference
background
PubMed Identifier
12773517
Citation
Reumaux D, de Boer M, Meijer AB, Duthilleul P, Roos D. Expression of myeloperoxidase (MPO) by neutrophils is necessary for their activation by anti-neutrophil cytoplasm autoantibodies (ANCA) against MPO. J Leukoc Biol. 2003 Jun;73(6):841-9. doi: 10.1189/jlb.1102567.
Results Reference
background
PubMed Identifier
10477614
Citation
Zhu X, Munoz NM, Kim KP, Sano H, Cho W, Leff AR. Cytosolic phospholipase A2 activation is essential for beta 1 and beta 2 integrin-dependent adhesion of human eosinophils. J Immunol. 1999 Sep 15;163(6):3423-9.
Results Reference
background
PubMed Identifier
12897749
Citation
Meliton AY, Munoz NM, Liu J, Lambertino AT, Boetticher E, Myo S, Myou S, Zhu X, Johnson M, Leff AR. Blockade of LTC4 synthesis caused by additive inhibition of gIV-PLA2 phosphorylation: Effect of salmeterol and PDE4 inhibition in human eosinophils. J Allergy Clin Immunol. 2003 Aug;112(2):404-10. doi: 10.1067/mai.2003.1637.
Results Reference
background
PubMed Identifier
12797494
Citation
Reid DW, Ward C, Wang N, Zheng L, Bish R, Orsida B, Walters EH. Possible anti-inflammatory effect of salmeterol against interleukin-8 and neutrophil activation in asthma in vivo. Eur Respir J. 2003 Jun;21(6):994-9. doi: 10.1183/09031936.03.00109702.
Results Reference
background
PubMed Identifier
12857718
Citation
Qiu Y, Zhu J, Bandi V, Atmar RL, Hattotuwa K, Guntupalli KK, Jeffery PK. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003 Oct 15;168(8):968-75. doi: 10.1164/rccm.200208-794OC. Epub 2003 Jul 11.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs