Pharmacogenetics Use For Further Treatment Improvement in childreN

Summary

There is large heterogeneity in treatment response to asthma medication and a one-size fits all approach based on current guidelines might not fit all children with asthma. It is expected that children with one or more variant alleles (Arg16Arg and Arg16Gly) within the beta2 adrenergic receptor (ADRB2) gene coding for the beta2-receptor have a higher risk to poorly respond to long-acting beta2-agonists (LABA) comparing to the Gly16Gly wildtype.

Aims To study whether ADRB2 genotype-guided treatment will lead to improvement in asthma control in children with uncontrolled asthma on inhaled corticosteroids compared with usual care.

Design A multicentre, double-blind, precision medicine, randomized trial will be carried out within 20 Dutch hospitals. 310 asthmatic children (6-17 years of age) not well controlled on a low dose of inhaled corticosteroids (ICS) will be included and randomized over a genotype-guided and a non-genotype-guided(control) arm. In the genotype-guided arm children with Arg16Arg and Arg16Gly will be treated with double dosages of ICS and with the Gly16Gly wildtype with add on LABA. In the control arm children will be randomized over both treatment options. Lung function measurements, questionnaires focussing on asthma control (ACT/c-ACT) and quality of life, will be obtained in three visits within 6 months. The primary outcome will be improvement in asthma control based on repeated measurement analysis of c-ACT or ACT scores in the first three months of the trial. Additional cost effectiveness studies will be performed.

Conclusion Currently, pharmacogenetics is not used in paediatric asthmas. This trial may pave the way to implement promising results for genotype-guided treatment in paediatric asthma in clinical practice.

Conditions

• Asthma in Children

Interventions

GENETIC

ADRB2-genotype guided treatment

This intervention assesses whether ADRB2 genotype-guided treatment leads to better asthma control after 3 months compared to usual care in children who are uncontrolled despite adherent and adequate use of ICS.

OTHER

Randomisation

In the control arm, children will be randomised over double dose ICS or ICS+LABA instead of treatment according to their genotype.

Sponsors & Collaborators

• Dutch Lung Foundation

  collaborator UNKNOWN

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  lead OTHER

Principal Investigators

• Anke-Hilse Maitland-van der Zee, Prof. Dr. · Academic Medical Center, Department of Respiratory Medicine

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

6 Years

Max Age

17 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-06-12

Primary Completion

2023-10-18

Completion

2023-10-18

Countries

• Belgium
• Netherlands
• Switzerland

Study Locations