Chronic Obstructive Pulmonary Disease (COPD) Biomarker Identification Study

NCT01780298 | Completed Results

• 1 other identifier: QASMC 202
• Study Type: observational
• Target: 252
• Locations: 1 country
• Sites: 1

Brief Summary

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. This case control study will be conducted at The Heart Lung Centre, London, UK. The study aims to determine biomarkers for the differentiation of subjects with COPD (GOLD Stage 1-2 and who are current smokers with a ≥ 10 pack year smoking history) and three matched control groups: one of non-smoking subjects (never smoked), one of ex-smokers and one of current smokers. COPD subjects will be matched to the non-COPD subjects by gender, age and ethnicity. The study will include a range of physiological measurements including lung function, computerized tomography scans (CT scans), cardio pulmonary exercise test and computerized multichannel lung sounds analysis (Stethographics). In addition, lung inflammation will be assessed by cellular and molecular biomarkers using e.g. transcriptomics and proteomics technologies.

Conditions

COPD

Keywords

COPD; Biomarkers; Cigarette Smoke; Lung Inflammation; FEV; Sputum

Outcome Measures

Primary Outcomes (9)

• Spirometry Measurement: Percentage of Predicted Forced Expiratory Volume in 1 Second (FEV1 %Pred)

  Up to 59 days

• Gas Transfer: Percentage of Predicted Total Diffusing Capacity of the Lungs for Carbon Monoxide (TLCO %Pred)

  Up to 59 days

• Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Central Airway Resistance at 5Hz (R5 %Pred)

  Up to 59 days

• Impulse Oscillometry (IOS) Measurements: Percentage of Predicted Reactance at 5 Hz (X5 % Pred)

  Up to 59 days

• Impulse Oscillometry (IOS) Measurements: Resonant Frequency (Fres)

  Up to 59 days

• Stethographics Measurements: Non-Weighted Acoustic Chronic Obstructive Pulmonary Disease Scores (ACOPDS)

  Stethographics analysis was performed using the 16-channel lung sound analyzer system STG1602 (Stethographics, Boston, MA, USA) following the supplier's recommendations. Lung sound data are obtained from an intermediate deeper-than-normal breath (pattern 2; P2). Each breath pattern is recorded for a minimum of 30 seconds allowing 3 to 6 breaths to be taken, with measurements completed over 3 to 4 minutes. Each of the 16 parameters derived from one measurement are evaluated and a score from 0 to 10 is assigned based on the value of the individual parameter. The total standard Acoustic COPD Score (ACOPDS) is calculated as the sum of the individual score for each parameter, which permits a maximum score of 160. Although this stethographics analysis system was considered experimental, a higher score was associated with poor health outcomes and a lower score with a better health state.

  Up to 59 days

• Dyspnoea Assessment: Modified Medical Research Council (MMRC) Dyspnoea Scale

  The MMRC scale uses a simple grading system to assess a subject's level of dyspnea (shortness of breath). Subjects were asked to grade the degree of breathlessness related to activities by choosing 1 of the following answers: * 0: Not troubles by breathlessness except on strenuous exercise * 1: Short of breath when hurrying or walking up a slight hill * 2: Walks slower than contemporaries on the level because of breathlessness, or has to stop for breath when walking at own pace * 3: Stops for breath after about 100 meters or after a few minutes on the level * 4: Too breathless to leave the house, or breathless when dressing or undressing.

  Up to 59 days

• Prediction of Mortality and Hospitalizations: Modified BODE Index (mBODE)

  The BODE Index is a 10-point scale to assess prognostic factors in COPD patients. Body mass index ("B"), airway obstruction ("O"), dyspnea ("D"), and exercise tolerance ("E") are each graded on a 4 point scale (0 to 3), except body mass index (0 or 1) . The final BODE Index value is the sum of the scores for each prognostic factor, where a higher BODE score indicates a higher risk of death. The modified BODE (mBODE) index as defined by Lopez-Campos (2010) was used in this study, and is composed of the following factors: * Body mass index: (0 or 1) * Degree of airflow obstruction (FEV1% Pred): (0 to 3) * Functional dyspnea (MMRC Dyspnoea Scale): (0 to 3) * Exercise capacity (VO2max): (0 to 3) Lopez-Campos, José Luis, et al. "Modified BODE indexes: Agreement between multidimensional prognostic systems based on oxygen uptake." International Journal of Chronic Obstructive Pulmonary Disease (2010): 133-140.

  Up to 59 days

• High-Resolution Computerised Tomography (HRCT) of the Chest

  CT scans were assessed by two radiologists. A scoring system from 0 to 4 was applied, depending upon the component: 1. Extent of disease (emphysema): 0=absent, 1=mild, 2=moderate, 3=severe, 4=very severe 2. Severity of bronchial dilatation: 0=none; 1=mild (1.5x to 2.5x diameter of pulmonary artery); 2=severe (\>2.5x diameter of pulmonary artery) 3. Traction bronchiectasis: 0=none; 1=mild (1.5x to 2.5x diameter); 2=severe (\>2.5x diameter). 4. Total bronchiectasis score derived by adding the bronchial dilatation and traction bronchiectasis scores 5. Bronchial wall thickening: 0=none; 1=0.5x; 2=0.5-1x; 3= \>1x the diameter of the adjacent pulmonary artery 6. Small airways disease: 0=absent, 1=mild, 2=moderate, 3=severe and 4=very severe The total score (higher score indicated a poor outcome) was derived from the mean of all scores. This is described in Chaudhary, Nveed, et al. "Physiological and biological characterization of smokers with and without COPD." F1000Research 6 (2017).

  Up to 59 days

Other Outcomes (6)

• Total Leukocytes and Differential Leukocytes Count in Sputum

  Up to 59 days

• Protein Markers as Determined by Proteomics Analysis of Induced Sputum

  Up to 59 days

• Lipid Markers as Determined by Lipidomic Analysis of Blood Samples

  Up to 59 days

Study Arms (4)

Group 1: COPD GOLD Stage 1-2

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

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

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

Subjects who have never smoked (non-smokers), and matched to the COPD cases by ethnicity, gender and age (within 5 years).

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

In this study, male and female subjects aged between 40-70 years will be included. All subjects must be matched by ethnicity, gender and age (within 5 years) of the subjects with COPD recruited in the study.

You may qualify if:

• Provision of signed written informed consent which includes genetic consent.
• Ability to comply with study procedures.
• Males and females aged 40-70 years inclusive.
• Have a body mass index (BMI) between 18 and 35 kg/m2 inclusive and minimum body weights of 50 kg.
• Have a normal physical examination, and have normal laboratory values, 12-lead ECG and vital signs (blood pressure, heart rate and respiratory rate), unless the Investigator considers an abnormality as not clinically significant.
• Ability to perform reproducible spirometry according to the American Thoracic Society and the European Respiratory Society (ATS/ERS) guidelines (American Thoracic Society, 2005).
• Ability to produce a minimum 0.1 gram sputum sample after induction with inhaled hypertonic saline.
• A clinical diagnosis of COPD according to the GOLD guidelines (stage 1-2).
• Current smokers with ≥10 pack-year smoking history.
• Demonstrate a post-bronchodilator ratio between forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) of \<70 % and FEV1 ≥50 % of predicted normal.
• Have never smoked tobacco products.
• Demonstrate normal lung function by post bronchodilator FEV1 ≥80 % of predicted normal, with no evidence of airway obstruction FEV1/FVC ratio ≥70 %.
• Have a sputum eosinophilia \<2 % and a sputum neutrophilia \<80 % from the sample collected at visit 1 (Belda et al., 2000).
• Be current smokers with defined smoking history of ≥10 pack years.
• Have normal lung function by post bronchodilator FEV1 ≥80 % of predicted normal, with no evidence of airway obstruction FEV1/FVC ratio ≥70 %.

You may not qualify if:

• Current evidence or recent history of any clinically significant disease or abnormality (other than COPD in the subjects with COPD group), which in the opinion of the Investigator, would put the subject at risk, or which would compromise the quality of the study data, including but not limited, to cardiovascular disease, myocardial infarction, cardiac failure, uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes, neurologic or neuromuscular disease, liver disease, gastrointestinal disease or electrolyte abnormalities.
• Females with a positive pregnancy test at visit 1 or 3.
• Females currently breastfeeding.
• Involvement in the planning and conduct of the study.
• Surgery or significant trauma within 3 months of visit 1.
• History of tuberculosis or other non-specific pulmonary diseases such as asthma.
• Symptoms, signs or laboratory findings suggestive of an ongoing infective illness as judged by the Investigator at visit 1 or 2.
• Participation in any clinical study with an investigational drug in the 4 months prior to visit 1, or participation in a study with a new formulation of a marketed drug in the 3 months prior to visit 1, or participation in a methodology study in the month prior to visit 1.
• Symptoms of any clinically significant illness within 2 weeks prior to visit 1.
• A significant history of alcohol abuse or consumption of more than the recommended units of alcohol per week (28 units for males and 21 units for females).
• A significant history of drug abuse (including benzodiazepines) or a positive test of drug abuse test at visit 1.
• Subjects, who in the opinion of the Investigator should not, for safety or compliance reasons, participate in the study.
• Use of prohibited medications.
• Subjects who have a first degree relative (parents, sibling or child) already enrolled in the study.
• Recent history of hospitalization due to an exacerbation of airway disease within 3 months of the screening visit or subjects with need for increased treatments for COPD within 6 weeks prior to the screening visit.

Sponsors & Collaborators

• Philip Morris Products S.A.: lead

Study Sites (1)

Heart Lung Centre, Queen Anne Street Medical Centre

London, United Kingdom

Location

Related Publications (4)

• Titz B, Sewer A, Schneider T, Elamin A, Martin F, Dijon S, Luettich K, Guedj E, Vuillaume G, Ivanov NV, Peck MJ, Chaudhary NI, Hoeng J, Peitsch MC. Alterations in the sputum proteome and transcriptome in smokers and early-stage COPD subjects. J Proteomics. 2015 Oct 14;128:306-20. doi: 10.1016/j.jprot.2015.08.009. Epub 2015 Aug 22.

  PMID: 26306861 RESULT

• Martin F, Talikka M, Hoeng J, Peitsch MC. Identification of gene expression signature for cigarette smoke exposure response--from man to mouse. Hum Exp Toxicol. 2015 Dec;34(12):1200-11. doi: 10.1177/0960327115600364.

  PMID: 26614807 RESULT

• Chaudhary N, Luettich K, Peck MJ, Pierri E, Felber-Medlin L, Vuillaume G, Leroy P, Hoeng J, Peitsch MC. Physiological and biological characterization of smokers with and without COPD. F1000Res. 2017 Jun 13;6:877. doi: 10.12688/f1000research.11698.2. eCollection 2017.

  PMID: 29862011 RESULT

• Titz B, Luettich K, Leroy P, Boue S, Vuillaume G, Vihervaara T, Ekroos K, Martin F, Peitsch MC, Hoeng J. Alterations in Serum Polyunsaturated Fatty Acids and Eicosanoids in Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD). Int J Mol Sci. 2016 Sep 20;17(9):1583. doi: 10.3390/ijms17091583.

  PMID: 27657052 DERIVED

Related Links

• Sputum transcriptomics
• Sputum proteomics
• Nasal scrapes transcriptomics

Biospecimen

Retention: SAMPLES WITH DNA

Proteomic investigations: Induced Sputum Transcriptomics investigations (mRNA and micro RNA): Whole Blood, Nasal Scrapes, Induced sputum cell pellet Genomic DNA sequencing: Whole blood Lipidomics: Whole blood

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Cigarette Smoking; Pneumonia

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Tobacco Smoking; Smoking; Behavior; Tobacco Use; Respiratory Tract Infections; Infections

Results Point of Contact

• Title: Julia HOENG, PhD
• Organization: Philip Morris Products S.A.

clinicaltrials.pmi@pmi.com

+41 (58) 242 2214

Study Officials

• Brian Leaker, MD

  Heart Lung Centre, Queen Anne Street Medical Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2013
• First Posted: January 31, 2013
• Study Start: July 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: January 14, 2025
• Results First Posted: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Anyone who wishes to access the data.

Locations

GB (1)