COPDNCT00147095
Regulation of Inflammatory Mediators in Chronic Obstructive Pulmonary Disease
An observational study of COPD and Emphysema, run by Imperial College London at 1 site in United Kingdom.
Trial summary
The aim of this study is to investigate the mechanisms whereby lung function is decreased in COPD. The hypothesis is that in diseases such as COPD, inflammatory cells including neutrophils, macrophages and lymphocytes migrate to the lung and release either more or different types of inflammatory mediators and/or… Read more about this study
- Who is it for?
- Ages 21 to 70 yearsHealthy volunteers can take part
- How many people
- 80 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2003to Feb 2005
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy non-smoking and smoking subjects, smoking participants with COPD
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Brompton Hospital/NHLI Imperial College London
London, SW3 6LY
About this study
The aim of this study is to investigate the mechanisms whereby lung function is decreased in COPD. The hypothesis is that in diseases such as COPD, inflammatory cells including neutrophils, macrophages and lymphocytes migrate to the lung and release either more or different types of inflammatory mediators and/or destructive enzymes compared to subjects without COPD. We aim to investigate these separate cell types in the blood of subjects with COPD and identify which genes are more highly expressed when compared to cells obtained from patients without COPD. We will also investigate the lung macrophages from these subjects to identify whether the same or different genes are expressed in these cells. We will isolate different leukocyte populations from the blood and extract ribonucleic acid (RNA) from these samples. The type and quantity of RNA in these samples is a reflection of the specific genes expressed in these cells. This RNA will be sent to Gene Logic and this company will test these samples to identify which genes have been expressed. Similar experiments will be performed using macrophages obtained following bronchoalveolar lavage of these subjects. We would aim to examine the responses of leukocytes from three groups of subjects, namely (i) non-smoking controls (ii) smokers without clinical or histological signs of COPD and (iii) smokers with COPD. The isolated leukocytes will either be immediately solubilized in solutions to purify RNA or we will then use these isolated cells in vitro and following stimulation investigate whether different genes are expressed or at a differential rate in the disease state. The objective is to identify which genes are specifically expressed in patients with COPD with a view to identify novel targets for drug therapy. We will examine both leukocytes derived from peripheral blood and macrophages obtained from bronchoalveolar lavage with the aim to determine whether differences attributable to disease can be identified in both circulating cells and those at the site of disease. This is a preliminary study to determine the profile of inflammatory mediator expression from leukocytes and as such power calculations to determine the number of subjects is not appropriate.
Read the 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.
- Keywords
- macrophages, neutrophils, lymphocytes
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Emphysema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| HEALTHY NON-SMOKER | Healthy non-smoker participants | |
| HEALTHY SMOKER | Healthy smoker participants | |
| COPD and smoking | Smoking participants with COPD |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2005 (estimated)
- Study startFeb 2003
- Primary completionFeb 2005
- Study completionFeb 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPDStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Gene Logic
- Responsible party
- Sponsor
- Investigators
- Louise E Donnelly, PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00147095
- Sponsor's protocol ID
- 02-207
- Other IDs
- DHTAB PN1259
- Status last verified
- Nov 2019
- First submitted
- 6 Sep 2005
- Last updated
- 14 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regulation of Inflammatory Mediators in Chronic Obstructive Pulmonary Disease
- ClinicalTrials.gov ID
- NCT00147095
- Acronym / sponsor ID
- 02-207
- Keywords
- macrophages, neutrophils, lymphocytes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Gene Logic
- Study start
- Feb 2003 (actual)
- Primary completion
- Feb 2005 (actual)
- Study completion
- Feb 2005 (actual)
- First posted
- 7 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to investigate the mechanisms whereby lung function is decreased in COPD. The hypothesis is that in diseases such as COPD, inflammatory cells including neutrophils, macrophages and lymphocytes migrate to the lung and release either more or different types of inflammatory mediators and/or destructive enzymes compared to subjects without COPD. We aim to investigate these separate cell types in the blood of subjects with COPD and identify which genes are more highly expressed when compared to cells obtained from patients without COPD. We will also investigate the lung macrophages from these subjects to identify whether the same or different genes are expressed in these cells. We will isolate different leukocyte populations from the blood and extract ribonucleic acid (RNA) from these samples. The type and quantity of RNA in these samples is a reflection of the specific genes expressed in these cells. This RNA will be sent to Gene Logic and this company will test these samples to identify which genes have been expressed. Similar experiments will be performed using macrophages obtained following bronchoalveolar lavage of these subjects. We would aim to examine the responses of leukocytes from three groups of subjects, namely (i) non-smoking controls (ii) smokers without clinical or histological signs of COPD and (iii) smokers with COPD. The isolated leukocytes will either be immediately solubilized in solutions to purify RNA or we will then use these isolated cells in vitro and following stimulation investigate whether different genes are expressed or at a differential rate in the disease state. The objective is to identify which genes are specifically expressed in patients with COPD with a view to identify novel targets for drug therapy. We will examine both leukocytes derived from peripheral blood and macrophages obtained from bronchoalveolar lavage with the aim to determine whether differences attributable to disease can be identified in both circulating cells and those at the site of disease. This is a preliminary study to determine the profile of inflammatory mediator expression from leukocytes and as such power calculations to determine the number of subjects is not appropriate.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HEALTHY NON-SMOKER | – | –Healthy non-smoker participants |
| HEALTHY SMOKER | – | –Healthy smoker participants |
| COPD and smoking | – | –Smoking participants with COPD |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy non-smoking and smoking subjects, smoking participants with COPD
Key inclusion criteria (26 listed)
- Healthy non-smoking subjects
- Age 21-70 years.
- No history of respiratory or allergic disease.
- Normal baseline spirometry as predicted for age, sex and height.
- Non-smokers.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Louise E Donnelly, PhD principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COPD and Emphysema, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2019.