To assess whether ADRB2 genotype-guided asthma treatment in children with persistend athma symptoms despite ICS treatment leads to better asthma control compared to non-genotype-guided asthma treatment.
ID
Source
Brief title
Condition
- Allergic conditions
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Improvement of asthma control based on repeated measurement analysis of
(childhood)-Asthma Control Test scores after 3 months.
Secondary outcome
Change in asthma control score at t=6 months, time to ACT >= 20 (continuous
variable), change in asthma related quality of life scores, change in fatigue
score, school absences, exacerbations (oral corticosteroids use, ER visits,
hospital admissions), time to first exacerbation, amount of changes in therapy
at t=3 months, change in lung function (FEV1 pre-and postbronchodilator) at t=3
and t=6, change in FeNO at t=3 and t=6.
Background summary
Asthma is the most chronic disease in children. There is a large variability in
treatment response to asthma medication and a one-size fits all approach might
not be optimal for all paediatric patients. In children who are not well
controlled on inhaled corticosteroïds (ICS), guidelines suggest to double the
dose of ICS or add a long acting beta-agonist (LABA). Variation in the gene
encoding the beta2 adrenergic receptor (ADRB2), has been associated in multiple
paediatric asthma populations with poor response to long-acting beta2 agonists
(LABA). Paediatric asthma patients carrying the risk variant might therefore
benefint more from doubling ICS dosages than from receiving LABAs.
Study objective
To assess whether ADRB2 genotype-guided asthma treatment in children with
persistend athma symptoms despite ICS treatment leads to better asthma control
compared to non-genotype-guided asthma treatment.
Study design
Dutch national, multi-centre randomized controlled double blind trial
Intervention
Participants will be randomized to 1) a genotype-guided treatment arm or 2) a
usual care (non-genotype guided) control arm. In the genotype-guided arm,
children will be treated based on their genotype of ADRB2 (single nucleotide
polymorphism rs1042713). Children homozygous for the risk variant (Arg16Arg)
and heterozygotes (Arg16Gly) will receive LABA. In the usual care arm, children
will be randomized between doubling ICS dosage or LABA treatment, the two most
common chosen options among respiratory paediatricians in the Netherlands when
children are uncontrolled despite low dosages of ICS.
Study burden and risks
Risks: nasal swabbing (soft tip swabs, Copan) provides a minimal burden to the
children, as is the donation of saliva and feces. Repeated lung function
measurements can be experienced as uncomfortable in case of spirometer induced
bronchoconstriction, which happens <3% in asthmatic children. We will monitor
this with repeated lung function measurements, and administer salbutamol 400
mcg if needed (pMDI with spacer). Furthermore, there are no risks for the
participation in the study. The risks associated with participation can be
considered negligible and the burden minimal.
This study includes minors, since the effect of the ADRB2 genotype on response
to asthma medication seems to be restricted to the paediatric population. This
patient group is expected to have the most benefit from prospective ADRB2
genotyping before starting treatment.
Benefits: chirldren may be more fastly controlled when genotyping results to
the best medication for the individual child.
We will set up a patient panel to assure that the intrests of the patients will
be served.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- Between 6-18 years of age
- Doctor's diagnosis of asthma based on patient history, FEV1 reversibility >=
12% ever and/or bronchial hyperresponsiveness ever.
- Current asthma symptoms (based on ACT (>= 12 years) or c-ACT (< 12 years)
score <= 19
- ICS use >= 3 months before inclusion (start dosage ICS, treatment step 2
according to childhood asthma guideline NVK)
- Adequate inhalation technique
- self-assessed good adherence to maintenance asthma treatment
- understanding of Dutch language
- Internet access at home, willing to fill in internet questionnaires
Exclusion criteria
- active smoking
- congenital heart disease
- serious lung disease other than asthma
- LABA use in the past 6 months
- omalizumab use
- ICU admission in the previous year
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| Other | 6727 |
| EudraCT | EUCTR2017-004424-29-NL |
| CCMO | NL63849.018.17 |