Exhaled Breath Metabolomic Biomarkers in the Acutely Breathless Patient

Healthy Clinical Trial

— EMBER  

Official title:

Exhaled Breath Metabolomic Biomarkers in the Acutely Breathless Patient

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03672994
• Other study ID #: 0569
• Status: Completed
• Start date: February 2, 2017
• Est. completion date: April 30, 2019

Study information

• Verified date: August 2018
• Source: University of Leicester
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 650
• Est. completion date: April 30, 2019
• Est. primary completion date: December 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Breathlessness
• Community-acquired Pneumonia
• COPD
• Dyspnea
• Healthy
• Heart Failure
• Pneumonia

Locations

Country	Name	City	State
United Kingdom	NIHR Leicester Biomedical Research Centre - Respiratory, Glenfield Hospital	Leicester	Leicestershire

Sponsors (8)

Lead Sponsor	Collaborator
University of Leicester	Advion Biosciences Ltd, B & S ANALYTIK GmbH, Engineering and Physical Sciences Research Council, UK, Loughborough University, Medical Research Council, Owlstone Ltd, University Hospitals, Leicester

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Discovery of exhaled breath biomarkers	To evaluate the sensitivity, specificity, positive and negative predictive value of metabolomic biomarkers in exhaled breath samples to identify acute breathlessness, defined as one or more of (i) patient defined acute breathlessness and/or a (ii) 1 unit increase in Extended Medical Research Council breathlessness score (eMRC)	0-6 months
Secondary	Patient defined breathlessness	Participants are asked to provide information on their state of breathlessness	visit 1a (first visit), visit 2 (0-6 months)
Secondary	COPD Assessment Test (CAT) (Questionnaire)	Evaluation and rehabilitation education guidance on the respiratory and motor functions of patients with chronic obstructive pulmonary disease. The CAT has a scoring range of 0-40, with Since COPD is a progressive disease, a fi xed target score for all patients cannot be set. In Practice, a target for improvement in individual patient CAT scores may be set, based on an holistic assessment of the patient. A change of 2 units suggests a meaningful difference. This test should be used in conjunction with the eMRC and forced expiratory volume in one second (FEV1) to determine COPD health assessment of participants.	visit 1a (first visit), visit 2 (0-6 months)
Secondary	NASA task load index	Evaluation breath testing work load using mental, physical, temporal, performance, effort and frustration. Participants are asked to mark a scale based on how demanding the task was for each of the domains above.	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Asthma quality of life questionaire (AQLQ)	Evaluation quality of life in asthmatic patients based on their level of activity, symptoms, environment and emotion.	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Asthma control questionnaire (ACQ)	Measure of asthma control	visit 1a (first visit), visit 2 (0-6 months)
Secondary	extended Medical Research Council (eMRC) Dyspnea Scale	Assessing respiratory breathlessness symptoms (Grade 0-5b, with Grade 0 being breathlessness with strenuous exercise to Grade 5b being breathlessness for daily activities like dressing).	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Visual analogue score (VAS) total and individual dyspnoea, cough and wheeze (100mm) scores	The participant is asked to place a mark (X) on the scale at the point that best describes their health currently. Minimum score 0mm (better outcome), maximum score 100mm (worse outcome) for each section of the scale (dyspnoea, cough, wheeze).	visit 1a (first visit), visit 2 (0-6 months)
Secondary	NewYork Heart Association Dyspnoea score (NYHA)	Assessing grades of breathlessness specifically designed for heart failure patients	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Sputum collection for assessment of purulence, cytology and metagenomics	Participants are asked to provide a spontaneous sputum sample assessing purulence, cytology and metagenomics	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Pre and post bronchodilator (BD) spirometry to assess lung function	To assess lung function	visit 1a (first visit), visit 2 (0-6 months)
Secondary	fraction exhaled nitric oxide (FeNO) assessing airway inflammation	To assess airway inflammation in asthmatics. Patients are asked to blow into a mouthpiece for few seconds which detects the amount of exhaled nitric oxide.	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Hand held oscillometry assessing small airway lung function	To assess small airway lung function	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Quadriceps ultrasound measuring quadriceps size as a degree of frailty	To assess degree of frailty and muscle breakdown during hospital admission. Participants have their quadriceps muscle size measured using an ultrasound machine.	visit 1a (first visit)
Secondary	Four meter gait	physical performance - measure of frailty	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Exacerbation history	participants are asked to provide information on recent exacerbations of airway disease	visit 1a (first visit), visit 2 (0-6 months)
Secondary	DECAF score assessing in hospital mortality in COPD patients	DECAF score has a minimum score of 1 (better outcome) and a maximum score of 6(worse outcome) used for assessment of severity of COPD exacerbation measures eMRC score, Eosinopenia, consolidation, acidemia and atrial fibrillation	visit 1a (first visit)
Secondary	CURB65 score assessing mortality in Pneumonia patients	CURB65 is used in assessment of 30 day mortality of Pneumonia based on confusion, urea, respiratory rate, blood pressure and age.Scores range from 1 (better outcome) to 5 (worse outcome)	visit 1a (first visit)
Secondary	BTS asthma severity score	BTS asthma severity score is used in assessment of asthma severity based on peak flow, respiratory rate, oxygen levels, altered level of consciousness, arrythmia, hypotension, cyanosis, silent chest and respiratory effort. Patients are then classified into mild (better outcome), moderate, severe and life threatening (worse outcome).	visit 1a (first visit)
Secondary	Meta analysis global group in chronic heart failure (MAGGIC - risk calculator)	Assessment of heart failure severity based on age, gender, diabetes, COPD, heart failure diagnosed in the last 18 months, current smoker, NYHA class, b blockers, ACEI or ARB, BMI, systolic BP, creatinine and ejection fraction	visit 1a (first visit)
Secondary	Sputum differential Cell Count	Differential Cell Count to assess inflammation at exacerbation events.	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Breath volatile organic compound (VOC) profiling	Participants are asked to provide a breath sample to measure VOC using Compact Mass Spectrometer (CMS), Gas chromatography ion mobility spectrometer (GC-IMS), gas chromatography mass spectrometer (GC-MS), Proton transfer reaction time of flight mass spectrometer (PTR-Tof-MS), gas chromatography gas chromatography mass spectrometer (GCxGC-MS).	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Serum/Plasma Inflammatory Biomarkers	To assess systemic inflammation. Plasma/ serum biomarkers are exploratory and we do not have a specific list of biomarkers yet.	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Full blood count (FBC)	Blood Biochemistry	visit 1a (first visit), visit 2 (0-6 months)
Secondary	C-reactive protein (CRP)	Blood Biochemistry	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Troponin-I	Blood Biochemistry	visit 1a (first visit), visit 2 (0-6 months)
Secondary	B-type naturitic peptide (BNP)	Blood biochemistry	visit 1a (first visit), visit 2 (0-6 months)
Secondary	RNA (PAXgene)	Blood Biochemistry	visit 1a (first visit), visit 2 (0-6 months)
Secondary	DNA (PAXgene)	Blood Biochemistry	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Age	Demographics	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Smoking status, calculated using pack years (no. of cigarettes smoked per day X no. of years smoked divided by 20	Demographics	visit 1a (first visit), visit 2 (0-6 months)
Secondary	BMI in kg/m^2	Demographics	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Gender	Demographics	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Heart rate	Vital signs	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Blood pressure	Vital signs	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Oxygen saturations	Vital signs	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Temperature	Vital signs	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Medical history	medical history	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Current medications	Medical history	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Physical examination	Physical examination	visit 1a (first visit), visit 2 (0-6 months)
Secondary	12 lead Electrocardiogram (ECG)	cardiac function	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Echocardiogram (ECHO)	cardiac function	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Chest Xray	Respiratory function	visit 1a
Secondary	Height	Demographics	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Weight	Demographics	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Ethnicity	Demographics	visit 1a (first visit), visit 2 (0-6 months)
Secondary	Review of adverse events and serious adverse events	Review of untoward medical occurrences	visit 1a (first visit), visit 2 (0-6 months)