Chronic Obstructive Pulmonary Disease (COPD) Biomarker Identification Study
Chronic obstructive pulmonary disease (COPD) is a common inflammatory disease of the airway affecting approximately 10% of individuals aged 40 years or more with a smoking history. The disease is characterized by an increase in numbers of airway white blood cells (neutrophils, lymphocytes and monocytes). Stimulation of white blood cells results in the release of different agents of inflammation. Some of these agents give an indication of the presence or severity of a disease when measured. These are called biomarkers.
This study will be conducted in the UK and will (a) identify existing and new biomarkers and (b) compare these amongst the 4 groups of subjects recruited for the study. The groups will consist of 60 COPD subjects, 60 non-smokers (never smoked), 60 ex-smokers and 60 current smokers, all aged 40-70 years. COPD subjects will be matched to the non-COPD subjects by gender, age and ethnicity.
Severe COPD is associated with elevated sputum neutrophil counts therefore sputum samples will be obtained. In order to identify other biomarkers, nasal samples collected by 3 different methods (scraping the inside of the nose with a plastic probe, washing the nostril with salty water and placing strips of filter paper in the nostril for 2 minutes), and blood samples will be also obtained. Other tests to determine the quantity and quality of proteins, a substance called ribonucleic acid (RNA and to extract deoxyribonucleic acid (DNA) will be performed on some of the collected samples. Other tests such as a chest CT scan, full lung function assessment and cardio-pulmonary exercise tolerance test will be also performed.
The study consists of 4 visits in total, plus the follow-up call, and can take a minimum of 14 days to a maximum of 66 days for each subject to fully complete the study.
|Study Design:||Observational Model: Case Control
Time Perspective: Cross-Sectional
|Official Title:||A Biomarker Study to Compare Gene and Protein Expression Profiles in Four Separate Groups of Subjects Including COPD Cases (GOLD Stage 1-2 and Current Smokers With a ≥ 10 Pack Year Smoking History) and Three Control Groups of Matched Non-smoking Subjects (Never Smoked), ex Smokers and Current Smokers, to Identify Novel Biomarkers, to Assess Standard Biomarkers of Inflammation and to Compare Inflammatory Cell Responses and Selected Markers of Inflammation in Blood, Induced Sputum and Nasal Samples.|
- Composite description of lung inflammation as assessed by cellular and molecular biomarkers [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]
- The total leucocyte and differential leucocyte count in sputum.
- Selected biomarkers of inflammation in blood, sputum and nasal fluid. Biomarkers of inflammation include, but are not limited to, the following: neutrophil elastase, IL1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-9, IL-12, IL-13, IL-17, TNFalpha, TGFbeta, GM-CSF, MCP-1alpha, TIMP-1, MMP8, MMP9, MMP12, IFN gamma and IP-10.
- Protein markers as determined by proteomics assays from blood, nasal lavage and induced sputum.
- mRNA and miRNA (transcriptomics) derived from nasal epithelial cells obtained by nasal scrapes .
- mRNA and miRNA (transcriptomics) derived from leucocytes obtained from blood samples.
- mRNA and miRNA (transcriptomics) derived from induced sputum.
- Genomic DNA sequencing from leukocytes obtained from blood samples.
- Lipid markers as determined by lipidomic assays from blood samples
- Composite descriptions of inflammation as assessed by Physiological and Clinical parameters. [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]
- Full lung function including lung volumes and transfer factor measurements.
- IOS measurements.
- Multichannel lung sound analysis measurements.
- Differential fractional exhaled nitric oxide (differential FENO).
- Differential exhaled breath temperature measurements.
- The stage of COPD with high resolution CT scan measurements and to compare quantitative CT measurements.
- Exercise capacity (VO2 max and SpO2 desaturation) measurements
- Demographic details.
- Validated QOL measurement (SF36).
- Modified Medical Council Dyspnea Scale (MMRC)
- General Questionnaire
Biospecimen Retention: Samples With DNA
Proteomic investigations: Blood serum, Induced Sputum and Nasal Lavage
Transcriptomics investigations (mRNA and micro RNA): Whole Blood, Nasal Scrapes, Induced sputum cell pellet
Genomic DNA sequencing: Whole blood
Lipidomics: Whole blood
|Study Start Date:||July 2011|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Group 1: COPD GOLD Stage 1-2
Sixty subjects with a clinical diagnosis of COPD, according to the GOLD guidelines (Stages 1-2), who are current smokers with at least a 10 pack-year smoking history.
Group 2: Current Cigarette Smokers
Sixty subjects who are current smokers with at least a 10 pack-year smoking history and matched to the COPD cases by ethnicity, gender and age (within 5 years).
Group 3: Ex-Smokers
Sixty subjects who are ex-smokers with at least a 10 pack-year smoking history who have not smoked for at least one year and matched to the COPD cases by ethnicity, gender and age (within 5 years).
Group 4: Never Smokers
Sixty subjects who have never smoked (non smokers) and matched to the COPD cases by ethnicity, gender and age (within 5 years).
A case control study with three matched control groups. At the screening visit, subject consent will be obtained prior to conducting any study related procedures. Informed consent may be obtained on registration/review visit at the Centre which is conducted prior to visit 1.
The screening visit will involve obtaining demographic data and medical history information as well as performing safety assessments such as vital signs measurements, electrocardiogram (ECG), and clinical laboratory tests. An induced sputum sample will be obtained to ensure that subjects can produce an adequate sputum sample. Smokers will receive information on smoking cessation at the screening visit and follow-up telephone call.
Subjects will attend the center on up to four further occasions if they meet the inclusion/exclusion criteria at screening. An additional visit (Visit 1a) may be scheduled for subjects who are unable to produce an adequate sputum sample at Visit 1. This will be at the discretion of the Investigator (or suitably qualified designee).
The subject will return for visit 2 (4 to 21 days after screening) once it is determined that the subject is eligible for the study. Visit 3 will be conducted within 3-14 days of the completion of visit 2. Visit 4 will be scheduled 3-14 days post visit 3. A follow up telephone call will be conducted 3-10 days post visit 4.
Subjects will undergo measurements of full lung function including lung volumes and transfer factors, differential exhaled nitric oxide (Differential FENO), impulse oscillatory (IOS), multichannel lung sound analysis, cardio-pulmonary exercise test with measurement of ventilator oxygen capacity (VO2 max) and oxygen saturation levels (SpO2), exhaled breath temperature, nasal sampling and sputum induction. All subjects will complete quality of life questionnaires (SF36 and QOL) and the Modified Medical Council (MMRC) Dyspnea Scale.
All subjects will undergo high resolution CT scan at visit 3 for the quantitative assessment of airway thickness and radiological evidence of emphysema. The staging of COPD will also be determined in subjects with COPD.
Blood samples will be obtained for clinical biochemistry and hematology. The measurement of biomarkers of inflammation will be performed on blood, sputum and nasal fluid samples. Additional biological material (blood and nasal respiratory epithelia obtained from nasal scrapes) will be collected for transcriptomics (mRNA and miRNA gene expression analyses). Proteomic evaluation will be conducted on blood, sputum and nasal fluid samples. Blood samples will be collected for future genome sequencing (genomics) and lipidomics sampling.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01780298
|London, United Kingdom|