Ignite Creation Date:
2024-05-05 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00147095
Status:
COMPLETED
Last Update Posted:
2019-11-14
First Post:
2005-09-06
Brief Title:
Regulation of Inflammatory Mediators in Chronic Obstructive Pulmonary Disease
Sponsor:
Imperial College London
Organization:
Imperial College London
Study Overview
Official Title:
Regulation of Inflammatory Mediators in Chronic Obstructive Pulmonary Disease
Status:
COMPLETED
Status Verified Date:
2019-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 andor 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
1 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
2 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
3 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 830 am after having fasted from midnight Subjects will have pre-treatment with atropine 06 mg iv and midazolam 5-10 mg iv Oxygen 3 lmin 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 09 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
4 Venous Blood Sampling 60 ml of blood will be taken by venopuncture
Details of interventions to subjects
1 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
2 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
3 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 830 am after having fasted from midnight Subjects will have pre-treatment with atropine 06 mg iv and midazolam 5-10 mg iv Oxygen 3 lmin 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 09 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
4 Venous Blood Sampling 60 ml of blood will be taken by venopuncture
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| DHTAB PN1259 | None | None | None |