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BROnchoalveolar Investigations of Never-smokers With Chronic Obstruction From the Swedish CardioPulmonary bioImage Study (BRONCOSCAPIS)

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by Asa Wheelock, Karolinska Institutet
Sponsor:
Collaborators:
Swedish Heart Lung Foundation
Lund University
Göteborg University
Linkoeping University
Uppsala University
Umeå University
Karolinska University Hospital
Lund University Hospital
Sahlgrenska University Hospital, Sweden
University Hospital, Linkoeping
Uppsala University Hospital
University Hospital, Umeå
Stockholm County Council, Sweden
Information provided by (Responsible Party):
Asa Wheelock, Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT03049202
First received: January 31, 2017
Last updated: February 7, 2017
Last verified: February 2017
  Purpose

Obstructive lung disease is an increasing global health problem of pandemic proportions, with COPD alone affecting >10% of the population. Smoking is the main and most well studies risk factor for developing COPD. However, chronic airway obstruction also in never-smoking populations has recently been recognized as an increasing health problem.

In the clinical segment (PI: Prof. C. Magnus Skold), 1000 subjects from the Swedish national SCAPIS study will be clinically well characterized in one of the six Swedish University Hospital Respiratory clinics (clinical site PIs: Anders Andersson, Leif Bjermer, Anders Blomberg, Christer Janson, Lennart Persson, Magnus Skold). This first screening includes all never-smokers with COPD identified in the SCAPIS study. A subset of 300 subjects from the groups of Healthy never-smokers, current-smokers with normal lung function, current-smokers with COPD, ex-smokers with COPD, and never-smokers with COPD will be selected for the Bronchoscopy segment, were sampling will be performed from a number of anatomical locations, including bronchial biopsies, airway epithelial brushings, and bronchoalveolar lavage. Serum, plasma, and urine samples will also be collected.

In the systems medicine segment (PI: Assoc. prof Asa M. Wheelock), alterations at the epigenetic, mRNA, microRNA, proteome, metabolome and microbiome level will be performed from multiple lung compartments (airway epithelium, alveolar macrophages, exosomes, and bronchoalveolar exudates). By means of biostatistics and bioinformatics approaches, specific mediators and molecular pathways critical in the pathological mechanisms of obstructive lung disease related to never-smoker disease phenotypes will be identified.

In the immunohistochemistry segment (PI: Prof. Jonas Erjefalt), a number of molecules of relevance for disease pathology will be investigated in bronchial biopsies collected from the 300 subjects in the Bronchoscopy segment.


Condition
Chronic Obstructive Pulmonary Disease Emphysema Chronic Bronchitis Airway Obstruction Smoking, Tobacco Gender

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: BROnchoalveolar Investigations of Never-smokers With CHronic Obstructive Lung Disease From the Swedish CardioPulmonary bioImage Study

Further study details as provided by Asa Wheelock, Karolinska Institutet:

Primary Outcome Measures:
  • Forced expiratory volume in 1 second (FEV1) [ Time Frame: Measured at baseline ]
    Calculated as percent predicted based on the European Coal and Steel Community reference values

  • Emphysema, as shown on chest CT scan [ Time Frame: Measured at baseline ]
    Based on lung densities < (-950) Hounsfield units (HU)

  • Airway wall thickness on chest CT scan [ Time Frame: Measured at baseline ]
    Based on lung densities in the range of (-750) - (-900) HU

  • COPD status (COPD participants versus control group participants) based on GOLD criteria [ Time Frame: Measured at baseline ]
    Calculated using, post-bronchodilator values defined as meeting the criteria based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) of a fixed FEV1/forced vital capacity (FVC) ratio < 0.7

  • COPD status (COPD participants versus control group participants) based on GLI criteria [ Time Frame: Measured at baseline ]
    Calculated using, post-bronchodilator values defined as meeting the Global Lung Initiative (GLI) ratio of FEV1/FVC below of lowest limit of normal z-score < (-1.64)


Secondary Outcome Measures:
  • Molecular phenotypes of never-smoker COPD group(s) as compared to control groups [ Time Frame: Measured at baseline ]
    mRNA, miRNA, proteomes, lipidomes and metabolomes will be quantified from airway exudates (BAL fluid), BAL cells, and airway epithelium (bronchial brushings)


Biospecimen Retention:   Samples With DNA
Mouth wash, bronchoalveolar lavage (BAL) cells, BAL fluid, bronchial wash (BW) cells, BW fluid, bronchial biopsies, airway epithelial brushings, serum, plasma, blood cells, and urine are collected and stored.

Estimated Enrollment: 1000
Actual Study Start Date: February 1, 2017
Estimated Study Completion Date: December 31, 2025
Estimated Primary Completion Date: June 1, 2020 (Final data collection date for primary outcome measure)
Groups/Cohorts
Never-smoker COPD participants
COPD patients with mild-to-moderate COPD (GOLD I-II) that have never smoked. Definition of never-smoker: Lifetime consumption of <100 cigarettes. No cigarettes the past 2 years.
Ex-smoker COPD participants
COPD patients with mild-to-moderate COPD (GOLD I-II) that stopped smoking. Definition of smoking: > 10 pack years. Definition of ex-smoker: > 2 years since smoke cessation.
Current-smoker COPD participants
COPD patients with mild-to-moderate COPD (GOLD I-II) that are currently smoking. Definition of smoking: > 10 pack years. Definition of current-smoker: > 10/cigarettes/dat the past 6 months.
Current-smoker healthy controls
Current-smokers that are otherwise healthy, with normal lung function. Definition of smoking: > 10 pack years. Definition of current-smoker: > 10/cigarettes/dat the past 6 months.
Never-smoker healthy controls
Healthy participants that have never smoked. Definition of never-smoker: Lifetime consumption of <100 cigarettes. No cigarettes the past 2 years.

Detailed Description:
Chronic Obstructive Pulmonary Disease (COPD) is an umbrella diagnosis defined by obstructive lung function impairments, and is likely to be caused by a multitude of etiologies including environmental exposures, genetic predispositions and developmental factors. Due to the heterogeneity of the disease, molecular and mechanistic sub-phenotyping of COPD represents an essential step to facilitate the development of relevant diagnostic and treatment options for this constantly growing patient group. In the BRONCHO-SCAPIS study, molecular sub-phenotypes of smoking-induced COPD are investigated. A particular focus relates to recent epidemiological indications of an increasing proportion of never-smokers developing the disease. The study encompasses profiling of mRNA, miRNA, proteomes, metabolomes and lipid mediators of from multiple lung compartments (airway epithelium, alveolar macrophages, exosomes, and bronchoalveolar exudates) using a range of 'omics platforms, in combination with extensive clinical phenotyping of early stage COPD patients, never-smokers, and smokers with normal lung function from both genders. The primary objective of the study is to identify molecular sub-phenotypes of never-smokers with COPD, specifically by correlating clinical phenotypes multi-molecular 'omics profiling from multiple lung compartments of early stage COPD patients compared to healthy and at-risk control populations. Secondary goals involve identification of subsets of prognostic/diagnostic biomarkers for classification of the defined subgroups, as well as relevant pharmaceutical targets.
  Eligibility

Ages Eligible for Study:   50 Years to 68 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The 1000 participants are recruited from the Swedish SCAPIS study, a cross sectional study screening 30,000 subjects across the six University Hospitals in Sweden, based on lung function criteria and questionnaire criteria collected during SCAPIS.
Criteria

Inclusion Criteria:

  • Spirometry of postbronchodilator forced expiratory volume in 1 second (FEV1) >50% of predicted level for all groups.
  • Spirometry of postbronchodilator FEV1 >80% of predicted level and FEV1/FVC ratio >0.70 for Healthy control groups
  • Spirometry of postbronchodilator FEV1/FVC ratio <0.70 for COPD groups.

Exclusion Criteria:

  • Smoking (for never-smoker groups)
  • Other lung diseases
  • Received antibiotics in the 3 months prior to study entry
  • Treatment with oral or inhaled glucocorticoids within past 3 months prior to study entry
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03049202

Contacts
Contact: Magnus Skold, MD, PhD +46 8 517 748 43 magnus.skold@ki.se
Contact: Asa M Wheelock, PhD +46 8 517 70664 asa.wheelock@ki.se

Locations
Sweden
Karolinska Institutet/Karolinska University Hospital Solna Recruiting
Stockholm, Sverige, Sweden, 17176
Contact: Magnus Skold, MD, PhD       magnus.skold@ki.se   
Contact: Asa M Wheelock, PhD       asa.wheelock@ki.se   
Principal Investigator: C. Magnus Skold, MD, PhD         
Principal Investigator: Asa M Wheelock, PhD         
Göteborg University / Sahlgrenska University Hospital Recruiting
Gothenburg, Sweden
Contact: Anders Andersson, MD         
Contact: Sara Tengvall, MD, PhD         
Linköping Unversity /Linköping University Hospital Recruiting
Linköping, Sweden
Contact: Lennart Persson, MD         
Lund University / Lund University Hospital Recruiting
Lund, Sweden
Contact: Leif Bjermer, MD         
Contact: Ellen Tufvesson, PhD         
Umeå University / Umeå University Hospital Recruiting
Umeå, Sweden
Contact: Anders Blomberg, MD         
Uppsala University / Uppsala University Hospital Recruiting
Uppsala, Sweden
Contact: Christer Janson, MD         
Contact: Helena Igelström, MD         
Sponsors and Collaborators
Karolinska Institutet
Swedish Heart Lung Foundation
Lund University
Göteborg University
Linkoeping University
Uppsala University
Umeå University
Karolinska University Hospital
Lund University Hospital
Sahlgrenska University Hospital, Sweden
University Hospital, Linkoeping
Uppsala University Hospital
University Hospital, Umeå
Stockholm County Council, Sweden
Investigators
Principal Investigator: Magnus Skold, MD, PhD Karolinska Institutet /Karolinska University Hospital
  More Information

Responsible Party: Asa Wheelock, Associate professor, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT03049202     History of Changes
Other Study ID Numbers: 2016/841-31/2
Study First Received: January 31, 2017
Last Updated: February 7, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Emphysema
Bronchitis
Bronchitis, Chronic
Airway Obstruction
Respiratory Tract Diseases
Pathologic Processes
Bronchial Diseases
Respiratory Tract Infections
Respiratory Insufficiency
Respiration Disorders

ClinicalTrials.gov processed this record on August 18, 2017