Exhaled Breath Metabolomic Biomarkers in the Acutely Breathless Patient

NCT ID: NCT03672994

Last Updated: 2020-01-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 650 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-02-02
• Study Completion Date: 2019-04-30

Brief Summary

An acute study carried out across three acute admissions units within Leicestershire. The study is aimed at discovery and validation of volatile organic compounds (VOCs) in exhaled breath. Participants will be recruited and tested within 24 hours of admission and once recovered, up to 6 months following discharge.

Detailed Description

A prospective real world observational study carried out across three acute admissions units. Participants with self-reported acute breathlessness, with a confirmed primary diagnosis of either acute heart failure, community acquired pneumonia and acute exacerbation of asthma or COPD will be recruited within 24 hours of admission. These will be matched to healthy volunteers from a similar environment. Additionally, school age children admitted with severe asthma will be evaluated and breath samples will be collected. All participants will undergo breath sampling on admission and upon recovery, up to six months following discharge. A range of online technologies including: proton-transfer-reaction mass spectrometry (PTR-MS), gas chromatography ion mobility spectrometry (GC-IMS), atmospheric pressure chemical ionisation- mass spectrometry (APCI-MS) and offline technologies including gas chromatography mass spectroscopy (GC-MS) and comprehensive two-dimensional gas chromatography-mass spectrometry (GCxGC-MS) will be utilised for VOC discovery and replication. For offline technologies a standardised CE marked breath sampling device (ReCIVA®) will be used. All recruited participants will be characterised using existing blood biomarkers including C - reactive protein (CRP), brain derived natriuretic peptide (BNP), Troponin-I and blood eosinophil levels and further evaluated using a range of standardised questionnaires, lung function testing including hand held forced oscillation technique (FOT) and fractional exhaled nitric oxide (FeNO), sputum cell counts and echocardiography for heart failure and COPD patients. Additional samples will be collected for bio-banking including urine, serum, plasma and sputum supernatants and plugs.

Conditions

Asthma; COPD; Heart Failure; Community-acquired Pneumonia; Healthy; Breathlessness

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Asthma

Patients with prior confirmed diagnosis of bronchial asthma

No interventions assigned to this group

Chronic Obstructive Pulmonary Disease

Patients with prior confirmed COPD

No interventions assigned to this group

Pneumonia

Patients with X-ray confirmed community acquired pneumonia

No interventions assigned to this group

Heart failure

Patients with confirmed heart failure

No interventions assigned to this group

Healthy volunteers

Healthy participants with no otherwise known cardiorespiratory condition

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

(i) Able to give informed consent for participation in the study. (ii) Male or Female, aged 16 years or above (adult cohort) and 5-15 years for paediatric patients attending the acute care paediatric pathway.

(iii) Capable (in the opinion of the EMBER clinical research investigator(s) of providing serial breath samples.

(iv) Diagnosed with acute breathlessness as one of the primary indicator reasons by the clinical acute care team. This is not a requirement for healthy subjects or matched controls.

(v) One of the indicator provisional diagnoses identified in section 7.1 following senior review by the clinical acute care team. This is not a requirement for healthy subjects or matched controls (vi) Able (in the Investigators opinion) and willing to comply with all study requirements.

(vii) Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.

(viii) Ability to understand English.

Exclusion Criteria

(i) Female participants who are known to be pregnant, lactating or planning pregnancy during the course of the study.

(ii) Current participation in a clinical trial of an investigative medicinal product or within 3 months or 5.5 half-lives of the IMP whichever is longer.

(iii) Active or clinically suspected pulmonary tuberculosis (iv) In the opinion of the treating physician, breath sampling during the acute admission would be clinically unsafe or inappropriate due to the patient's condition or poor prognosis. Examples include malignancy or autoimmune disease with anticipated survival of under 1 year, and chronic renal replacement therapy.

(v) Unable or unwilling to give informed consent by visit 1b. (vi) Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.

• Minimum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

Engineering and Physical Sciences Research Council, UK

OTHER

Sponsor Role: collaborator

Loughborough University

OTHER

Sponsor Role: collaborator

University Hospitals, Leicester

OTHER

Sponsor Role: collaborator

Owlstone Ltd

INDUSTRY

Sponsor Role: collaborator

B & S ANALYTIK GmbH

UNKNOWN

Sponsor Role: collaborator

Advion Biosciences Ltd

UNKNOWN

Sponsor Role: collaborator

University of Leicester

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Salman Siddiqui, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Leicester

Locations

NIHR Leicester Biomedical Research Centre - Respiratory, Glenfield Hospital

Leicester, Leicestershire, United Kingdom

Countries

United Kingdom

References

Ibrahim W, Wilde M, Cordell R, Salman D, Ruszkiewicz D, Bryant L, Richardson M, Free RC, Zhao B, Yousuf A, White C, Russell R, Jones S, Patel B, Awal A, Phillips R, Fowkes G, McNally T, Foxon C, Bhatt H, Peltrini R, Singapuri A, Hargadon B, Suzuki T, Ng LL, Gaillard E, Beardsmore C, Ryanna K, Pandya H, Coates T, Monks PS, Greening N, Brightling CE, Thomas P, Siddiqui S. Assessment of breath volatile organic compounds in acute cardiorespiratory breathlessness: a protocol describing a prospective real-world observational study. BMJ Open. 2019 Mar 8;9(3):e025486. doi: 10.1136/bmjopen-2018-025486.

Reference Type: DERIVED

PMID: 30852546 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

0569

Identifier Type: -

Identifier Source: org_study_id