* To define the characteristics of children with severe asthma and severe pre school wheeze in terms of clinical features, physiology and biomarker profiles and to compare these with patients with mild-moderate asthma and wheeze* To repeat the…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The study will assess and integrate multiple parameters in terms of clinical,
functional, cellular, molecular and patient reported outcomes for developing
phenotype *handprints* of severe asthma and pre school wheeze. For each
parameter a number of endpoints have been selected which will be used for the
following goals:
i. The characterization into phenotypic handprints of patients with severe
asthma and pre school wheeze and the comparison of these characteristics with
those with mild to moderate asthma and mild to moderate pre school wheeze.
ii. To enable the linking of molecular targets for drug intervention with the
pathophysiology of severe asthma and pre school wheeze
iii. Based upon the integration of data collected from severe asthma and pre
school wheeze patients, classifiers and predictors will be developed. This will
form the basis of the initial phenotype handprint.
Secondary outcome
Nvt
Background summary
Children with severe asthma and severe pre school wheeze (from herein referred
to collectively as *severe asthma*) are a heterogeneous patient group with
frequent exacerbations and/or progressive airways obstruction despite high
levels of therapy. Development of new treatments for such patients is hampered
by heterogeneous pathogenesis, lack of consensus on diagnostic criteria,
difficulty in translating pre-clinical human and animal models to drug efficacy
and absence of biomarkers that predict therapeutic efficacy.
U-BIOPRED aims to overcome the bottlenecks in drug development for severe
asthma by a focused and stepwise strategy based on an unbiased analysis of
multi-dimensional invasive and non-invasive biomarkers (phenotype handprints).
The use of biomarker profiles comprised of various types of high-dimensional
data from severe asthma and severe pre school wheeze cohorts and controls,
integrated by an innovative systems biology approach into distinct phenotype
handprints, will enable significantly better prediction of the clinical course
and therapeutic efficacy than single or even clustered biomarkers of one data
type, and will identify novel targets.
Study objective
* To define the characteristics of children with severe asthma and severe pre
school wheeze in terms of clinical features, physiology and biomarker profiles
and to compare these with patients with mild-moderate asthma and wheeze
* To repeat the measurement of clinical variables and biomarker profiles during
longitudinal follow up of the severe asthma and severe pre school wheeze
cohorts, including during severe exacerbations, and to compare these to
baseline measures
* To use the baseline and longitudinal characteristics to determine phenotype
handprints by combining high dimensional datasets using a systems biology
approach
* To develop phenotype handprints which will enable improved clinical
understanding and which will be used to determine clinical progression and
efficacy of interventions
Study design
Multi-centre prospective observational study
Study burden and risks
There is a major unmet need for improved treatments for patients with severe
asthma. The overall objective of this study, to develop phenotype handprints
which will enable improved clinical understanding which will be used to
determine clinical progression and efficacy of interventions, is considered to
be ethically justified. The procedures which will be used in the study have all
been carried out safely in patients with severe asthma and in most cases are
part of routine clinical practice. Most procedures are non-invasive. The most
invasive procedure, bronchoscopy, has been used extensively in patients,
including children, with severe asthma to assess airway inflammation.
Bronchoscopy will not be carried out in children as part of the study protocol
but if a bronchoscopy is being carried out for clinical reasons consent will be
sought to obtain additional samples.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Severe school aged asthma cohort: 6-17yrs old, persistent asthma symptoms or frequent severe exacerbations or persistent airflow limitation despite the prescription of high dose ICS or prescription of maintenance OCS
Mild-moderate school aged asthma cohort: 6-17yrs old, controlled asthma symptoms (according to GINA guidelines) with the prescription of low to moderate dose ICS
Severe pre school wheeze cohort: 1-5yrs old, persistent symptoms or frequent severe exacerbations despite the prescription of high dose ICS (or failed trial) or prescription of maintenance OCS
Mild-moderate pre school wheeze cohort: 1-5yrs old, controlled symptoms (according to GINA guidelines) with the prescription of low to moderate dose ICS (or failed trial).
See protocol page 35 to 40 for protocol specific inclusion criteria.
Exclusion criteria
1. As a result of medical interview, physical examination or screening investigation the responsible physician considers the child unfit for the study.
2. The subject has a history of drug or other allergy, which, in the opinion of the responsible 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 *37 weeks gestation
7. The child had changed medication within 4 weeks of the screening assessment (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).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL34765.018.11 |