Inhaled Steroid Reduces Systemic Inflammation in COPD

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
University of British Columbia
ClinicalTrials.gov Identifier:
NCT00175565
First received: September 11, 2005
Last updated: July 26, 2010
Last verified: July 2010
  Purpose

Systemic inflammation is present in chronic obstructive pulmonary disease (COPD), which has been linked to cardiovascular morbidity and mortality. We determined the effects of oral and inhaled corticosteroids on serum markers of inflammation in patients with stable COPD.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Emphysema
Chronic Bronchitis
Drug: inhaled fluticasone 500 mcg b.i.d.
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Effects of Fluticasone On Systemic Markers of Inflammation in Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • Change in serum C-reactive protein (CRP) levels

Secondary Outcome Measures:
  • Change in serum interleukin-6 and monocyte chemoattractant protein-1 levels

Estimated Enrollment: 50
Study Start Date: January 2002
Estimated Study Completion Date: July 2003
Detailed Description:

We recruited patients aged 45 to 80 years, who had stable symptoms of COPD in the previous 3 months before study entry. All patients had a forced expiratory volume in one second (FEV1) after bronchodilation with 400 mcg salbutamol that was 25 to 90% of predicted, a change of less than 20% of predicted FEV1, 30 minutes following bronchodilation, and a FEV1/forced vital capacity (FVC) of less than 75%. Patients also had a history of at least 10 pack-years of smoking or prolonged exposure (>10 years) to noxious gases (e.g. diesel fumes).

At the first visit, patients, who were taking inhaled corticosteroids, were asked to immediately discontinue the use of these medications. They were allowed to take other anti-COPD medications. None of the patients took theophyllines at the time of study entry and no new medications were commenced between the first and second visits. The patients returned 4 weeks later for a second visit, at which point, they were randomized into one of the three arms of the trial: placebo capsules and a placebo puffer, fluticasone (500 mcg twice daily) and placebo capsules, or prednisone (30 mg once daily) and a placebo puffer. The trial period lasted 2 weeks. Patients were then assigned to fluticasone (500 mcg twice daily) for 8 weeks in an un-blinded fashion, followed by an additional 8 weeks of fluticasone at 1000 mcg twice daily. At each visit, we measure the participants' serum C-reactive protein (CRP) level using nephelometry in accordance with recommendations from Center for Disease Control and the American Heart Association. We also measured serum concentrations of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). IL-6 was measured because it is a powerful signaling cytokine for CRP expression by the liver and is a known, independent risk factor for cardiovascular events.22,23 MCP-1 was measured because it may play a central role in the pathogenesis of COPD24 and by itself is a known risk factor for atherosclerosis, myocardial infarction and cardiac deaths. All samples were analyzed in duplicate.

For analytic purposes, continuous variables that were not normally distributed (including CRP values) were log-transformed to achieve normality. We used a paired t-test to compare the log-transformed CRP values between visit 2 (i.e. at the time of randomization) and visit 3 (at the end of the randomized trial phase) within each treatment group. Similarly, using visit 2 as the referent CRP value, we used paired t-tests to compare log-transformed CRP values across the visits. To assess whether there was a gradient in the log-transformed CRP values between placebo, fluticasone and prednisone groups, we also used a Mantel-Haenszel test for trend. We reasoned a priori that oral prednisone, a more potent systemic corticosteroid than inhaled fluticasone, would have the largest effect on CRP, followed by fluticasone. Linear regression was used to examine the association between changes in interleukin-6 and log-transformed CRP values between visit 1 and 2 and between visit 2 and 3. Continuous variables are expressed as meanSD, unless otherwise specified.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • stable symptoms of COPD in the previous 3 months before study entry; forced expiratory volume in one second (FEV1) after bronchodilation with 400 mcg salbutamol that was 25 to 90% of predicted, a change of less than 20% of predicted FEV1, 30 minutes following bronchodilation, and a FEV1/forced vital capacity (FVC) of less than 75%; history of at least 10 pack-years of smoking or prolonged exposure (>10 years) to noxious gases (e.g. diesel fumes).

Exclusion Criteria:

  • active malignancy; unable to follow instructions; patients taking any anti-inflammatory medications
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00175565

Locations
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2R7
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, V6Z 1Y7
Sponsors and Collaborators
University of British Columbia
GlaxoSmithKline
Investigators
Principal Investigator: Paul Man, MD University of British Columbia
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00175565     History of Changes
Other Study ID Numbers: 4027
Study First Received: September 11, 2005
Last Updated: July 26, 2010
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
inflammation
trial
fluticasone

Additional relevant MeSH terms:
Bronchitis
Bronchitis, Chronic
Emphysema
Pulmonary Emphysema
Inflammation
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Pathologic Processes
Fluticasone
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 17, 2014