- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03672994
Exhaled Breath Metabolomic Biomarkers in the Acutely Breathless Patient (EMBER)
Study Overview
Status
Detailed Description
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Leicestershire
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Leicester, Leicestershire, United Kingdom, LE3 9QP
- NIHR Leicester Biomedical Research Centre - Respiratory, Glenfield Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Prospective participants with self reported acute breathlessness, either requiring admission or a change in baseline treatment, presenting within University Hospitals of Leicester (UHL).
Patients with confirmed acute airway exacerbation or heart failure decompensation as part of other research studies at the NIHR Leicester BRC may also be included.
Age- and/or home environment matched adult/spousal/parent and sibling healthy volunteers will be recruited where possible on the admissions unit or in the research units across both sites at a separate visit.
A stable state control population will also be recruited to compare with the unstable state. This will consist of participants with a confirmed diagnosis matched with the acute care population but not in the exacerbation state.
Description
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.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Asthma
Patients with prior confirmed diagnosis of bronchial asthma
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Chronic Obstructive Pulmonary Disease
Patients with prior confirmed COPD
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Pneumonia
Patients with X-ray confirmed community acquired pneumonia
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Heart failure
Patients with confirmed heart failure
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Healthy volunteers
Healthy participants with no otherwise known cardiorespiratory condition
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Discovery of exhaled breath biomarkers
Time Frame: 0-6 months
|
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)
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0-6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient defined breathlessness
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
|
Participants are asked to provide information on their state of breathlessness
|
visit 1a (first visit), visit 2 (0-6 months)
|
COPD Assessment Test (CAT) (Questionnaire)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
|
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.
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visit 1a (first visit), visit 2 (0-6 months)
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NASA task load index
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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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)
|
Asthma quality of life questionaire (AQLQ)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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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)
|
Asthma control questionnaire (ACQ)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Measure of asthma control
|
visit 1a (first visit), visit 2 (0-6 months)
|
extended Medical Research Council (eMRC) Dyspnea Scale
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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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).
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visit 1a (first visit), visit 2 (0-6 months)
|
Visual analogue score (VAS) total and individual dyspnoea, cough and wheeze (100mm) scores
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
|
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).
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visit 1a (first visit), visit 2 (0-6 months)
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NewYork Heart Association Dyspnoea score (NYHA)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Assessing grades of breathlessness specifically designed for heart failure patients
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visit 1a (first visit), visit 2 (0-6 months)
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Sputum collection for assessment of purulence, cytology and metagenomics
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Participants are asked to provide a spontaneous sputum sample assessing purulence, cytology and metagenomics
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visit 1a (first visit), visit 2 (0-6 months)
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Pre and post bronchodilator (BD) spirometry to assess lung function
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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To assess lung function
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visit 1a (first visit), visit 2 (0-6 months)
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fraction exhaled nitric oxide (FeNO) assessing airway inflammation
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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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.
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visit 1a (first visit), visit 2 (0-6 months)
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Hand held oscillometry assessing small airway lung function
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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To assess small airway lung function
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visit 1a (first visit), visit 2 (0-6 months)
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Quadriceps ultrasound measuring quadriceps size as a degree of frailty
Time Frame: visit 1a (first visit)
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To assess degree of frailty and muscle breakdown during hospital admission.
Participants have their quadriceps muscle size measured using an ultrasound machine.
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visit 1a (first visit)
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Four meter gait
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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physical performance - measure of frailty
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visit 1a (first visit), visit 2 (0-6 months)
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Exacerbation history
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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participants are asked to provide information on recent exacerbations of airway disease
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visit 1a (first visit), visit 2 (0-6 months)
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DECAF score assessing in hospital mortality in COPD patients
Time Frame: visit 1a (first visit)
|
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
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visit 1a (first visit)
|
CURB65 score assessing mortality in Pneumonia patients
Time Frame: visit 1a (first visit)
|
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)
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visit 1a (first visit)
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BTS asthma severity score
Time Frame: visit 1a (first visit)
|
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).
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visit 1a (first visit)
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Meta analysis global group in chronic heart failure (MAGGIC - risk calculator)
Time Frame: visit 1a (first visit)
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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
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visit 1a (first visit)
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Sputum differential Cell Count
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Differential Cell Count to assess inflammation at exacerbation events.
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visit 1a (first visit), visit 2 (0-6 months)
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Breath volatile organic compound (VOC) profiling
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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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).
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visit 1a (first visit), visit 2 (0-6 months)
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Serum/Plasma Inflammatory Biomarkers
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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To assess systemic inflammation.
Plasma/ serum biomarkers are exploratory and we do not have a specific list of biomarkers yet.
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visit 1a (first visit), visit 2 (0-6 months)
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Full blood count (FBC)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Blood Biochemistry
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visit 1a (first visit), visit 2 (0-6 months)
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C-reactive protein (CRP)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Blood Biochemistry
|
visit 1a (first visit), visit 2 (0-6 months)
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Troponin-I
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Blood Biochemistry
|
visit 1a (first visit), visit 2 (0-6 months)
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B-type naturitic peptide (BNP)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Blood biochemistry
|
visit 1a (first visit), visit 2 (0-6 months)
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RNA (PAXgene)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Blood Biochemistry
|
visit 1a (first visit), visit 2 (0-6 months)
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DNA (PAXgene)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Blood Biochemistry
|
visit 1a (first visit), visit 2 (0-6 months)
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Age
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Demographics
|
visit 1a (first visit), visit 2 (0-6 months)
|
Smoking status, calculated using pack years (no. of cigarettes smoked per day X no. of years smoked divided by 20
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
|
Demographics
|
visit 1a (first visit), visit 2 (0-6 months)
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BMI in kg/m^2
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Demographics
|
visit 1a (first visit), visit 2 (0-6 months)
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Gender
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Demographics
|
visit 1a (first visit), visit 2 (0-6 months)
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Heart rate
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Vital signs
|
visit 1a (first visit), visit 2 (0-6 months)
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Blood pressure
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Vital signs
|
visit 1a (first visit), visit 2 (0-6 months)
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Oxygen saturations
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Vital signs
|
visit 1a (first visit), visit 2 (0-6 months)
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Temperature
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Vital signs
|
visit 1a (first visit), visit 2 (0-6 months)
|
Medical history
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
|
medical history
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visit 1a (first visit), visit 2 (0-6 months)
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Current medications
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
|
Medical history
|
visit 1a (first visit), visit 2 (0-6 months)
|
Physical examination
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Physical examination
|
visit 1a (first visit), visit 2 (0-6 months)
|
12 lead Electrocardiogram (ECG)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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cardiac function
|
visit 1a (first visit), visit 2 (0-6 months)
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Echocardiogram (ECHO)
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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cardiac function
|
visit 1a (first visit), visit 2 (0-6 months)
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Chest Xray
Time Frame: visit 1a
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Respiratory function
|
visit 1a
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Height
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
|
Demographics
|
visit 1a (first visit), visit 2 (0-6 months)
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Weight
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
|
Demographics
|
visit 1a (first visit), visit 2 (0-6 months)
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Ethnicity
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Demographics
|
visit 1a (first visit), visit 2 (0-6 months)
|
Review of adverse events and serious adverse events
Time Frame: visit 1a (first visit), visit 2 (0-6 months)
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Review of untoward medical occurrences
|
visit 1a (first visit), visit 2 (0-6 months)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Salman Siddiqui, Professor, University of Leicester
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0569
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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