Clinical trial NCT01982162: Longitudinal Assessment of Children With Severe Asthma and Severe Pre-school Wheeze
Official title: Protocol for the European Multi-Centre Study Understanding Severe Asthma Longitudinal Assessment of Children With Severe Asthma and Severe Pre-school Wheeze
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Keywords: Sputum
Clinical cohorts
Smokers
Asthma
Biopsies
Severe asthma
Collaborative research
Phenotyping
Lipidomics
Transcriptomics
Proteomics
Paediatric cohort
Systems Biology
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2013-11-13
Enrollment: 300
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * Severe school aged asthma cohort: persistent symptoms or frequent severe exacerbations or persistent airflow limitation
* Mild-moderate school aged asthma cohort: controlled or partially controlled asthma symtomps
* Severe pre school wheeze cohort: persistent symptoms or frequent severe exacerbations
* Mild-moderate pre school wheeze cohort: controlled symptoms or partially controlled

Brief summary: Cross-sectional study to characterize cohorts of children with asthma and healthy controls in terms of clinical features, physiological measurements and non-invasive measurement of biomarkers and develop phenotype handprints for children with severe asthma


Eligibility criteria: Inclusion Criteria:

1. Parent / guardian must be able to give written informed consent prior to participation in the study, which includes ability to comply with the requirements and restrictions listed in the consent form. Informed consent must be obtained prior to undertaking any study procedures.
2. Assent should be obtained from all children in the study where appropriate.
3. Male or female subject aged between 1 - 17 years inclusive at screening.
4. The parent / guardian, or where appropriate the child must be able to read, comprehend, and write at a sufficient level to complete study related materials.
5. Subjects will be allowed to enrol in other studies while taking part on this study. However, Permission from the Scientific Board must be obtained to enrol or allow the continued participation of a subject enrolled in another study.

Exclusion Criteria:

1. As a result of medical interview, physical examination or screening investigation the physician responsible considers the child unfit for the study.
2. The subject has a history of drug or other allergy, which, in the opinion of the responsable physician, contra-indicates their participation.
3. Subject is female who is pregnant or lactating or up to 6 weeks post partum or 6 weeks cessation of breast feeding. If a woman is subsequently found to have been pregnant at the time of an assessment data from that assessment will not be included in the analyses
4. The child has participated within 3 months of the first dose in a study using a new molecular entity, or the first dose in any other study investigating drugs or having participated within three months in a study with invasive procedures. Any U-BIOPRED assessments should be deferred until 3 months after the first dose or invasive procedure. Permission from the Scientific Board must be obtained to enroll or allow the continued participation of a child enrolled in another study.
5. Those who, in the opinion of the investigator, have a risk of non-compliance with study procedures.
6. Prematurity ≤35 weeks gestation
7. The child had changed asthma medication within 4 weeks of the screening assessment(except those using the Symbicort maintenance and reliever therapy (SMART) regime)(assessment should be deferred)
8. History or current evidence of an upper or lower respiratory infection or symptoms (including common cold) within 2 weeks of baseline assessment (assessment should be deferred).
9. The child has had a severe exacerbation (requiring ER attendance or hospital admission and/or a course of high dose OCS for at least 3 days duration) within 4 weeks of the baseline assessment (assessment should be deferred).

Primary outcomes:
measure: Asthma exacerbations
timeFrame: 3 years
measure: Lung function decline over the course of the study
timeFrame: 3 years
measure: Changes in asthma medication
timeFrame: 3 years
measure: Daily symptoms and short acting beta agonist (SABA) usage
timeFrame: 3 years
measure: Asthma control questionnaire (ACQ) at baseline and changes over the course of the study
timeFrame: 3 years
measure: Upper airway symptoms as assessed by the sino-nasal outcomes test (SNOT) at baseline and changes over the course of the study
timeFrame: 3 years
measure: Sleep and daytime drowsiness as assessed by the Epworth sleepiness scale at baseline and changes over the course of the study
timeFrame: 3 years
measure: Measurement of pulmonary function including spirometry, plethysmography, bronchodilator reversibility and respiratory impedance by forced oscillation technique
timeFrame: 3 years
measure: Radiological parameters such as computerized tomography (CT) scan, including assessment of lung structure
timeFrame: 3 years
measure: Measurement of inflammatory cell counts in blood, sputum and bronchoalveolar lavage (BAL)
timeFrame: 3 years
measure: Histopathology of bronchial biopsies in a sub group of subjects
timeFrame: 3 years
measure: Transcriptomics, proteomics and metabolomics will be used on samples such as blood, urine and endobronchial biopsies
timeFrame: 3 years
measure: Quality of life as assessed by the asthma quality of life questionnaire (AQLQ)
timeFrame: 3 years
measure: Anxiety and depression as assessed by the hospital anxiety and depression scale (HADS)
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Copenhaguen Unversity Hospital, Copenhaguen, Denmark
name: Hans Bisgaard, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Astrid Lindgren Children's Hospital, Stockholm, Sweeden
name: Gunila Hedlin, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department Respiratory medicine Pediatrics Insespital University of Bern, Bern, Switzerland
name: Philip Latzin, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Academic Medical Centre University of Amsterdam, Amsterdam, The Netherlands
name: Peter Sterk, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College of London, London, UK
name: Andrew Bush, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Southampton General Hospital, Southampton, UK
name: Graham Roberts, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Wythenshawe Hospital, Manchester, UK
name: Claire Murray, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Loza MJ, Djukanovic R, Chung KF, Horowitz D, Ma K, Branigan P, Barnathan ES, Susulic VS, Silkoff PE, Sterk PJ, Baribaud F; ADEPT (Airways Disease Endotyping for Personalized Therapeutics) and U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome Consortium) investigators. Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study. Respir Res. 2016 Dec 15;17(1):165. doi: 10.1186/s12931-016-0482-9.
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citation: Fleming L, Murray C, Bansal AT, Hashimoto S, Bisgaard H, Bush A, Frey U, Hedlin G, Singer F, van Aalderen WM, Vissing NH, Zolkipli Z, Selby A, Fowler S, Shaw D, Chung KF, Sousa AR, Wagers S, Corfield J, Pandis I, Rowe A, Formaggio E, Sterk PJ, Roberts G; U-BIOPRED Study Group. The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts. Eur Respir J. 2015 Nov;46(5):1322-33. doi: 10.1183/13993003.00780-2015. Epub 2015 Sep 24.
citation: Shaw DE, Sousa AR, Fowler SJ, Fleming LJ, Roberts G, Corfield J, Pandis I, Bansal AT, Bel EH, Auffray C, Compton CH, Bisgaard H, Bucchioni E, Caruso M, Chanez P, Dahlen B, Dahlen SE, Dyson K, Frey U, Geiser T, Gerhardsson de Verdier M, Gibeon D, Guo YK, Hashimoto S, Hedlin G, Jeyasingham E, Hekking PP, Higenbottam T, Horvath I, Knox AJ, Krug N, Erpenbeck VJ, Larsson LX, Lazarinis N, Matthews JG, Middelveld R, Montuschi P, Musial J, Myles D, Pahus L, Sandstrom T, Seibold W, Singer F, Strandberg K, Vestbo J, Vissing N, von Garnier C, Adcock IM, Wagers S, Rowe A, Howarth P, Wagener AH, Djukanovic R, Sterk PJ, Chung KF; U-BIOPRED Study Group. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J. 2015 Nov;46(5):1308-21. doi: 10.1183/13993003.00779-2015. Epub 2015 Sep 10.