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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT00116402
First received: June 28, 2005
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: fluticasone and salmeterol
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of the Mechanism of Synergism Between Fluticasone (FP) and Salmeterol in Preventing Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

Resource links provided by NLM:


Further study details as provided by University of Chicago:

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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: January 2005
Study Completion Date: October 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID
Drug: fluticasone and salmeterol
  1. will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID
  2. will start with salmeterol 50 mcg BID first and then crossover to combination therapy with fluticasone 220 mcg BID.
Active Comparator: 2
salmeterol 50 mcg BID then crossover to combination therapy with fluticasone 220 mcg BID
Drug: fluticasone and salmeterol
  1. will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID
  2. will start with salmeterol 50 mcg BID first and then crossover to combination therapy with fluticasone 220 mcg BID.

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

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00116402

Locations
United States, Illinois
Department of Medicine, Pulmonary & Critical Care Section, The University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
GlaxoSmithKline
Investigators
Principal Investigator: Imre Noth, M.D. University of Chicago
  More Information

Publications:

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT00116402     History of Changes
Other Study ID Numbers: 13426B
Study First Received: June 28, 2005
Last Updated: December 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Chicago:
COPD
Chronic Obstructive
Pulmonary Disease
Inhaled Corticosteroids
Airway Inflammation
Bronchoscopy

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Salmeterol
Fluticasone
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 26, 2014