Plain English Summary
Background and study aims
It is believed that lung diseases can change certain chemicals in people’s blood, saliva, urine and chest fluids. These chemicals or ‘biomarkers’ may be detectable even before a patient develops symptoms or changes are seen on hospital scans and chest X-rays. Non-invasive tests are much more preferred by patients so a great deal of focus is being applied to discovering early detection biomarkers in biofluids that are easy to access, such as saliva or urine. Quick, objective tests that are simple for patients would allow more rapid and earlier diagnosis at scale allowing for more timely interventions. A better understanding of the molecules in these diseases also opens up potential new
treatments. In this study, new gene and protein technologies currently only available in Universities will be used to measure combinations of the most promising molecules and microbes(biomarkers) from sputum (a mixture of saliva and mucus coughed up from the chest), blood, saliva, urine, pleural (lung) fluid and any biopsy samples from people attending hospital with lung diseases and compare them with samples from people with other lung diseases and healthy volunteers.
Who can participate?
Adults with COPD, adults suspected of having lung cancer and healthy volunteers and people with other lung diseases of the same age.
What does the study involve?
Participants attend an appointment at which they are asked some questions about their health. They are then asked to breathe deeply into a tube measuring the amount of carbon monoxide in your breath and spit into a collection container. Finally, a blood sample and sample of urine are collected. If the participant is having a sample taken of the lung or of fluid from the lung as part of their normal care, an extra one may be taken.
Over the next 10 years, when a participant goes into hospital, further sputum, urine and blood samples are taken.
What are the possible benefits and risks of participating?
The results will not affect direct care so there are no direct benefits of taking part but it should improve understanding of the diseases and help diagnose them earlier and more accurately in the future.
There are no direct risks of participating apart from the discomfort of a blood test and inconvenience of providing a spit and urine test.
Where is the study run from?
Participants are recruited from Prince Philip Hospital, Glangwili Hospital and Bronglais General Hospital and analysis of samples takes place in the Institute of Biological Environmental and Rural Sciences, Aberystwyth University (UK)
When is the study starting and how long is it expected to run for?
February 2016 to February 2026
Who is funding the study?
1. TENOVUS Wales (UK)
2. Knowledge Economy Skills Scholarships (KESS) ERDF via Aberystwyth University (UK)
3. Knowledge Without Borders Exchange Scholarships (Brazil)
Who is the main contact?
Professor Keir Lewis
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
IRAS number 187325
Study information
Scientific title
Application of metabolomics and microbiome sequencing in diagnosing and monitoring lung disease (COPD, Lung cancer, asthma, infections)
Acronym
Study hypothesis
There are non-invasive biomarkers which may be used as measurable indicators of the presence or severity of pulmonary diseases. These biomarkers may include changes in the metabolome, lipidome, proteome or in the microbiome of various human biofluids.
Literature review:
O’Shea K, Cameron SJS, Lewis K E, Liu C, Mur LAJ. Metabolomic-based biomarker discovery for lung cancer diagnosis: A case study. Biochimica et Biophysica Acta. 2016 Jul 14. pii: S0304-4165(16)30246-X. doi: 10.1016/j.bbagen.2016.07.007
Cameron SJ, Lewis KE, Beckmann M, Allison GG, Ghosal R, Lewis PD, Mur LA. The metabolomic detection of lung cancer biomarkers in sputum Lung Cancer. Lung Cancer; 2016; 94:88-95. doi: 10.1016/j.lungcan.2016.02.006.
Cameron SJ, Lewis KE, Huws SA, Lin W, Hegarty MJ, Lewis PD, Mur LA, Pachebat JA. Metagenomic Sequencing of the Chronic Obstructive Pulmonary Disease Upper Bronchial Tract Microbiome Reveals Functional Changes Associated with Disease Severity. PLoS One. 2016;11(2):e0149095. doi: 10.1371/journal.pone.0149095
Mironas A, Cameron S, O’Shea K, Lewis P, Mur L, Lewis KE. Exploiting metabolomic approaches to aid in the diagnosis of lung cancer. Proc European Resp Society. 2016
Cameron S, Lewis KE, Beckman M, Allsion G, Ghosal R, Lewis P, Mur I. Metabolomic profiling of clinical sputum samples reveals novel biomarkers for the early identification of lung cancer patients. Proc European Resp Society. 2014;43 (Suppl 58): 504
Ethics approval
Wales REC 7, 02/02/2016, ref: 16/WA/0036
Study design
Multi-centre observational longitudinal case-control study
Primary study design
Observational
Secondary study design
Case-control study
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
See additional files
Condition
Pulmonary diseases (COPD, lung cancer, asthma and others)
Intervention
Following provision of written, informed consent, participants attending hospital or their GP for their respiratory condition will be asked questions regarding their age, illness and treatments. They will be asked to provide a sputum / saliva sample, venous blood and urine sample. If they are having another procedure as part of routine care (e.g pleural aspiration, bronchoscopy etc) an additional sample of that tissue (pleural fluid or bronchial ashing / biopsy) will be taken for research purposes at the same time.
Participants will be requested to provide sputum, urine and blood samples whenever they attend hospital Including if they become unwell) i.e. opportunistic sampling for up to 10 years. We don't have specific time points.
Intervention type
Biological/Vaccine
Phase
Drug names
Primary outcome measure
1. Sensitivity and specificity of metabolomics screening (sputum, blood and urine) of diagnosing lung cancer (clinical-pathological diagnosis at 12 months) versus age matched controls area under the curve (AUC) analysis at baseline
2. Sensitivity and specificity of metabolomics screening (sputum, blood and urine) of diagnosing COPD (defined using clinical GOLD criteria) versus age matched controls i.e. area under the curve (AUC) analysis at baseline
Secondary outcome measures
No secondary outcome measures
Overall trial start date
21/02/2016
Overall trial end date
21/02/2026
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Subjects: patients with a diagnosis of respiratory disease and eventually healthy control volunteers. These will conform to the following categories.
COPD:
1. Patients suffering from COPD according to current standard criteria
2. Age over 40 years
3. Ex or current smokers of at least 10 pack-years
4. Post bronchodilator FEV1/FVC<0.70 and FEV1<80% predicted
Lung Cancer:
1. Patients referred by their GPs or other specialists with possible diagnosis of lung cancer
2. Have a smoking history, asbestos exposure or other suspicious symptoms including breathlessness, chest pain, cough, weight loss or exhibits an abnormal chest X-ray
Healthy Controls:
1. Spouses and family members of COPD patients
2. Smokers attending our secondary care smoking cessation service
3. No symptoms or known diagnoses of lung disease.
Patients with lung disease other than COPD or Lung Cancer: depending on resources the study will be expanded to include other controls with asthma, bronchiectasis, fibrosis or lung other diseases.
Participant type
Mixed
Age group
All
Gender
Both
Target number of participants
2000
Participant exclusion criteria
No exclusion criteria have been defined, except for the good condition of collected samples and reliability of the information provided to the reseachers by the particiapants.
Recruitment start date
12/05/2016
Recruitment end date
21/02/2026
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Prince Philip Hospital
Bryngwyn Mawr
Llanelli
SA14 8QF
United Kingdom
Trial participating centre
Glangwili Hospital
Dolgwili Road
Carmarthen
SA31 2AF
United Kingdom
Trial participating centre
Bronglais General Hospital
Caradog Road
Aberystwyth
SY23 1ER
United Kingdom
Trial participating centre
Aberystwyth University
Institute of Biological Environmental and Rural Sciences (IBERS)
Penglais Campus
Aberystwyth
SY23 3FL
United Kingdom
Sponsor information
Organisation
Hywel Dda University Health Board
Sponsor details
Corporate Offices
Ystwyth Building
St Davids Park
Jobs Well Road
Carmarthen
SA31 3BB
United Kingdom
+44 1437 773813
chris.tattersall@wales.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
TENOVUS Wales
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Knowledge Economy Skills Scholarships (KESS) ERDF via Aberystwyth University
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Knowledge Without Borders Exchange Scholarships (Brazil)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Peer reviewed papers and conference abstracts.
IPD Sharing plan:
Participant level data will be stored in a repository in password protected computer databases and source data will be kept in lever arch paper files within the secure Clinical Research Centre at Prince Philip Hospital for 5 years then stored for up to 25 years according to Health Board Standard Operating Procedures and UK Human Tissue Authority License approvals.
1. Persistent weblink: http://public-odp.nihr.ac.uk/QvAJAXZfc/opendoc.htm?document=CRNCC_Users%2FFind%20A%20Clinical%20Research%20Study.qvw&host=QVS%40win-qs1ilmcfh2h&anonymous=true&sheet=SH75&bookmark=Document\BM02&select=LB572,=StudyID=30816
2. Process for requesting access: written requests to Chief Investigator
3. Data is pseudo-anonymised
4. Any ethical or legal restrictions have all been approved through hospital R&D approvals and loco-regional Ethics approvals.
Intention to publish date
31/12/2016
Participant level data
Stored in repository
Basic results (scientific)
Publication list
Publication citations
Additional files
- ISRCTN16657101_PIS_07Feb16_V2.doc Uploaded 07/03/2017