- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00147095
Regulation of Inflammatory Mediators in Chronic Obstructive Pulmonary Disease
Study Overview
Detailed Description
This study involves a comparison of the inflammatory responses of leukocytes derived from 3 separate subject groups. The aim of the study is to compare the responses of leukocytes from patients with COPD with subjects that smoke and healthy non-smokers. One part of the study will involve isolation of different leukocyte populations from blood from each of the subject groups. In a second part of the study, we will examine the expression of inflammatory mediators in leukocytes derived from bronchoalveolar lavage samples from patients with COPD, smokers without COPD and healthy non-smokers. In subjects that are willing to participate, we will compare blood derived leukocytes and cells derived from those undergoing BAL, although not every subject will provide both blood and BAL samples. The isolated leukocytes (both from blood and BAL) will be used for in vitro experiments to determine the differences in gene expression in inflammatory cells from patients with COPD.
Details of interventions to subjects
- Medical History and Physical Examination A full medical history and physical examination (including height and weight) will be performed on the initial screening visit, in addition to that recorded in the clinical case notes.
- Respiratory Assessments Forced Expiratory Volume per second (FEVI) will be measured using a dry wedge spirometer (Vitalograph, Buckingham, UK) and expressed as a percent of predicted value. Subjects will be trained in the use of the apparatus before beginning the study. The baseline value at each visit will be measured after at least fifteen minutes of quiet rest, and will be taken as the highest of three readings made at one-minute intervals. Single readings only will be taken at other times.
- Endoscopic Bronchoscopy An operator approved by the Royal Brompton Ethics Committee will perform all bronchoscopies. The bronchoscopist that will perform these procedures is Dr Borja Cosio. Subjects will attend the bronchoscopy suite at 8.30 am after having fasted from midnight. Subjects will have pre-treatment with atropine (0.6 mg iv) and midazolam (5-10 mg iv). Oxygen (3 l/min) will be administered via nasal prongs throughout the procedure and oxygen saturation monitored with a digital oximeter. Using local anaesthesia with lidocaine (4%) to the upper airways and larynx, a fibreoptic bronchoscope (Olympus BF10 Key-Med) will be passed through the nasal passages into the trachea. Bronchoalveolar lavage (BAL) will be performed from the right middle lobe using warmed 0.9% NaCl with 4 successive aliquots of 60 ml. This is well-tolerated in subjects with COPD. Patients may experience pharyngeal irritation following the procedure; there is a 5% chance of fever following the procedure. Subjects undergoing bronchoscopy for clinical reasons will also be included in this study.
- Venous Blood Sampling 60 ml of blood will be taken by venopuncture.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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London, United Kingdom, SW3 6LY
- Royal Brompton Hospital/NHLI Imperial College London
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Healthy non-smoking subjects
All normal volunteers will meet the following criteria:
- Age 21-70 years.
- No history of respiratory or allergic disease.
- Normal baseline spirometry as predicted for age, sex and height.
- Non-smokers.
- No history of upper respiratory tract infection in the preceding six weeks.
- Not taking regular medication
COPD subjects COPD is diagnosed according to American Thoracic Society, European Respiratory Society and British Thoracic Society guidelines by the doctors in Professor Barnes' COPD clinic.
All COPD volunteers will meet the following criteria:
- Age between 40-75 years.
- A smoking history of at least 20 pack years. ( 1 pack year = 20 cigarettes per day for 1 year)
- FEV1:FVC ratio of <0.7, post-bronchodilator FEV1 of <85% predicted, reversibility with inhaled beta2-agonist of <15% of predicted FEV1: all three criteria are required.
- Current smokers or smokers who had ceased smoking for at least 6 months.
- No history of exacerbation, oral steroid or antibiotic use within the preceding 6 weeks.
- Normal serum alpha-1 antitrypsin level.
- No history of other respiratory or allergic disease.
- No evidence of atopy on skin prick testing to common aeroallergens (grass pollen, cat hair, house dust mite or Aspergillus fumigatus These tests will have already been performed as part of routine assessment in Professor Barnes' COPD clinic and we will not need to repeat them for this study.
Healthy Smokers
All healthy smoking volunteers in trials will meet the following criteria:
- Age 21-70 years.
- Smoking history of at least 10 pack years. (1 pack year = 20 cigarettes per day for 1 year).
- No history of respiratory or allergic disease.
- Normal baseline spirometry as predicted for age, sex and height.
- No history of upper respiratory tract infection in the preceding six weeks.
- Not taking regular medication.
Exclusion Criteria:
- Subjects will not included in this study if they meet any of the following exclusion criteria:
- Clinically significant findings in the medical history or on physical examination other than those of COPD in the COPD group.
- Pregnant women or mothers who are breastfeeding.
- Subjects who are unable to give informed consent.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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HEALTHY NON-SMOKER
Healthy non-smoker participants
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HEALTHY SMOKER
Healthy smoker participants
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COPD and smoking
Smoking participants with COPD
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Louise E Donnelly, PhD, Imperial College London
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 02-207
- DHTAB PN1259
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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