Cigarette Smoke Nasal and Whole Blood Challenge in Patients With Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by:
Imperial College London
ClinicalTrials.gov Identifier:
NCT00159341
First received: September 8, 2005
Last updated: August 12, 2008
Last verified: August 2008
  Purpose

This is a clinical research study to assess whether after exhaling a single cigarette smoke through the nose there are changes in the inflammatory cells and proteins of nasal secretions.

A single blood sample from each subject will be stimulated with cigarette smoke in the laboratory to see the effects on inflammatory blood cells.

Comparison of findings between smokers with COPD and "Healthy" smokers will be carried out.

We hypothesize that some subjects have amplified inflammatory response to a single cigarette, and these will be those subjects who develop chronic obstructive pulmonary disease (COPD) after decades of smoking. We hope to develop an acute challenge model that relates to the causation of COPD. When studying the effects of new drugs, these may be detected in small numbers of patients in a challenge situation, when we would need to study many more unchallenged patients to demonstrate drug effects. In clinical research on asthma and allergy, the nasal allergen challenge has been a very successful model, and we hope to validate a comparable model for COPD.


Condition Intervention Phase
Lung Diseases, Obstructive
Procedure: Nasal lavage
Procedure: Nasal filter paper
Procedure: Blood sampling
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Cigarette Smoke Nasal and Whole Blood Challenge in Patients With COPD

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Changes in the cytology and inflammatory mediator content of nasal exudates [ Time Frame: Single timepoint ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of nasal inflammatory response to smoke in patients with COPD with relevant controls [ Time Frame: Single timepoint ] [ Designated as safety issue: No ]
  • Comparison of inflammatory response in blood following cigarette smoking in patients with COPD and relevant controls [ Time Frame: Single timepoint ] [ Designated as safety issue: No ]
  • Comparison of nasal challenge with blood challenge [ Time Frame: Single timepoint ] [ Designated as safety issue: No ]
  • Develop a nasal challenge model to test novel anti-inflammatoy therapies for COPD [ Time Frame: Single timepoint ] [ Designated as safety issue: No ]
  • Identification of potential biomarkers for therapeutic trials in COPD [ Time Frame: Single timepoint ] [ Designated as safety issue: No ]
  • Definition of novel drug targets for potential new anti-inflammatory therapies [ Time Frame: Single timepoint ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: September 2005
Study Completion Date: December 2006
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Nasal lavage
    Nasal lavage was carried out at specified timepoints
    Procedure: Nasal filter paper
    Nasal filter paper was placed at specified timepoints
    Procedure: Blood sampling
    Blood sampling was performed as a routine safety check
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria (COPD Smokers):

  • Smokers currently on at least 5 cigarettes per day, with a history of >10 pack years
  • Post-bronchodilator FEV1 >30% of predicted and < 80% of predicted
  • Pre-bronchodilator FEV1/FVC of <70%
  • With or without chronic simple bronchitis

Exclusion criteria (COPD Smokers):

  • History of asthma, allergy (including rhinitis/eczema)
  • Reversibility : an increase in FEV1 that is >400ml from the baseline pre- bronchodilator value (bronchodilate with salbutamol 400g delivered from a metered dose inhaler (MDI) into a spacer).

Inclusion criteria (for "Healthy" Smokers):

  • Smokers currently on at least 5 cigarettes per day, with a history of >10 pack years
  • FEV1 >90% of predicted, FEV1/FVC of >70%
  • Cannot have chronic simple bronchitis
  • Age, sex, smoking history matched to COPD Smokers

Exclusion criteria (for "Healthy" Smokers):

  • History of asthma, allergy (including rhinitis/eczema
  • Reversibility: an increase in FEV1 that is both >400ml from the baseline pre-bronchodilator value (bronchodilate with salbutamol 400mcg delivered from a metered dose inhaler (MDI) into a spacer)P
  • Pregnancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00159341

Locations
United Kingdom
National Heart & Lung Institue Clinical Studies Unit, Imperial College London
London, United Kingdom, SW3 6HP
Sponsors and Collaborators
Imperial College London
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Trevor T Hansel, BSc MSc PhD National Heart & Lung Institute, Imperial College London
  More Information

Additional Information:
Publications:
- Vachier I et al.Inflammatory features of nasal mucosa in smokers with and without COPD. Thorax 2004; 59:303-307. - Naclerio RM et al. Mediator release after nasal airway challenge with allergen. Am Rev Respir Dis 1983; 128:597-602. - Greiff L et al. The 'nasal pool' device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions. Clin Exp Allergy 1990; 20:253-259. - Alam R et al. Development of a new technique for recovery of cytokines from inflammatory sites in situ. J Immunol Methods 1992; 155:25-29. - Weido AJ et al. Intranasal fluticasone propionate inhibits recovery of chemokines and other cytokines in nasal secretions in allergen-induced rhinitis. Ann Allergy Asthma Immunol 1996; 77:407-415. - Meltzer EO, Jalowayski AA. Nasal cytology in clinical practice. Am J Rhinol 1988; 2:47-54. - Fishwick D et al. Immunologic response to inhaled endotoxin: changes in peripheral cell surface markers in normal individuals. J Occup Environ Med 2004; 46:467-472. - Mudway IS, Kelly FJ. An investigation of inhaled ozone dose and the magnitude of airway inflammation in healthy adults. Am J Respir Crit Care Med 2004; 169:1089-1095. - Rahman I et al. Glutathione, stress responses, and redox signalling in lung inflammation. Antioxidants & Redox Signalling 2005; 7:42-59. - Koechlin C et al. Does systemic inflammation trigger local exercise-induced oxidative stress in COPD? Eur Respir J 2004; 23:538-544.

Responsible Party: Dr Trevor Hansel, NHLI Clinical Studies Unit
ClinicalTrials.gov Identifier: NCT00159341     History of Changes
Other Study ID Numbers: 05/Q0404/84
Study First Received: September 8, 2005
Last Updated: August 12, 2008
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
cigarette smoke
nasal
whole blood
cytokines
chemokines
nasal fluid
filter paper

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 16, 2014