Clinical trial NCT04865575: Systems Pharmacology Approach to Uncontrolled Pediatric Asthma
Official title: Systems Pharmacology Approach to Uncontrolled Pediatric Asthma (SysPharmPediA)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pediatric Asthma
Uncontrolled Asthma
Keywords: Systems Pharmacology
Omics
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: University of Maribor, Maribor, Slovenia.
name: University Children's Hospital, University of Regensburg, Regensburg, Germany
name: Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.
name: University of the Basque Country (UPV/EHU)
name: Hospital Universitario Donostia, San Sebastián, Spain.
name: Instituto de Salud Carlos III
name: Utrecht University, Utrecht, the Netherlands.
name: Karolinska Institutet
First posted: 2021-04-29
Enrollment: 145
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Four tertiary care centers from four European countries (the Netherlands, Germany, Spain, and Slovenia) recruited 145 asthmatic children and adolescents (6-17 years old). All centers obtained approval from their local medical ethics committee (ethics committee of University Regensburg, Germany (18-1034-101); Clinical Research Ethics Committee of the Basque Country, Spain (PI2015075 (SO)); Medical Ethics Committee of the University Medical Center Utrecht (UMC Utrecht), Utrecht, the Netherlands (NL55788.041.15); National Medical Ethics Committee, Slovenia (0120-569/2017/4)) and written informed consents were collected from the parents/caregivers and/or the recruited children when appropriate.

Brief summary: Background:

Asthma is a heterogeneous respiratory disease and the most common chronic disease in children. A small subset of children has continuous poor asthma control despite appropriate adherence to asthma medication. There is a clinical need to identify these children as early as possible to optimize treatment and/or to find therapeutic alternatives. Therefore, the "Systems Pharmacology approach to uncontrolled Pediatric Asthma" (SysPharmPediA) study was set up.

Objective:

To establish a cohort of pediatric moderate-to-severe uncontrolled and controlled patients with asthma in order to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach.

Methods:

In this multicenter observational case-control study, moderate-to-severe asthmatic children (n=145, age 6-17 years), were included in specialized hospitals in four European countries (Netherlands, Germany, Spain and Slovenia). Recruited subjects were selected based on good asthma control (controlled asthmatics, n=54) or poor asthma control / recurrent exacerbations (uncontrolled asthmatics, n=91). Comprehensive details concerning demographics, current and past patient/family history and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics and metabolomics will be evaluated from multiple collected, relatively non-invasive, samples of from the recruited individuals, such as: blood, feces, saliva, nasal swabs and exhaled breath. Follow-up visits were performed 6 and 12 months after inclusion.


Eligibility criteria: Inclusion Criteria:

General:

* Between 6-17 years of age
* Doctor diagnosis of asthma

In addition to the general criteria, a case with uncontrolled asthma (case group A) should meet:

* Asthma treatment Global INitiative of Asthma (GINA) step 3 or higher

  ≥ 1of the following criteria (based on the guideline 'Childhood Asthma' of the section paediatric pulmonology of the Dutch Society of Paediatricians, 2007):
* Frequent exacerbations requiring OCS use (≥1 in the past year) and/or
* Severe exacerbations requiring hospitalization or ER visits in the past year and/or
* ACQ/ACT scores indicating uncontrolled asthma

In addition to the general criteria, a case with an acute exacerbation (case group B) should meet:

* Asthma treatment Global INitiative of Asthma (GINA) step 2 or higher
* Current severe asthma exacerbation requiring hospitalization

In addition to the general inclusion criteria, a control (controlled asthma) should meet the following criteria:

* Asthma treatment Global INitiative of Asthma (GINA) step 3 or higher
* Lack of severe exacerbations requiring OCS use or hospitalizations or ER visits in the past year
* ACQ/ACT scores indicating well controlled asthma or few reported asthma symptoms during asthma checks in the past year.

Exclusion Criteria:

* Recent use of a course of antibiotics (\< 1 month). This will affect the microbiome analyses.

A patient can be re-screened 1 month after the use of the antibiotic treatment has finished.

Primary outcomes:
measure: Saliva and stool microbiome
timeFrame: Baseline
measure: Exhaled breath metabolome
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
measure: Age
timeFrame: Baseline (+ follow-up at 6 and 12 months after baseline inclusion)
measure: Sex
timeFrame: Baseline (+ follow-up at 6 and 12 months after baseline inclusion)
measure: BMI
timeFrame: Baseline (+ follow-up at 6 and 12 months after baseline inclusion)
measure: Uncontrolled asthma
timeFrame: Baseline (+ follow-up at 6 and 12 months after baseline inclusion)
measure: Exacerbations
timeFrame: Baseline (+ follow-up at 6 and 12 months after baseline inclusion)
measure: Spirometry
timeFrame: Baseline
measure: Pediatric Asthma Quality of Life Questionnaire (PAQLQ)
timeFrame: Baseline (+ follow-up at 6 and 12 months after baseline inclusion)
measure: Atopy
timeFrame: Baseline (+ follow-up at 6 and 12 months after baseline inclusion)
measure: Current asthma medication intake
timeFrame: Baseline (+ follow-up at 6 and 12 months after baseline inclusion)
measure: Asthma severity
timeFrame: Baseline (+ follow-up at 6 and 12 months after baseline inclusion)
Locations:
city: Regensburg
country: Germany
facility: University Regensburg
city: Utrecht
country: Netherlands
facility: Utrecht University
city: Maribor
country: Slovenia
facility: University of Maribor
city: San Sebastián
country: Spain
facility: University of the Basque Country
city: Santa Cruz De Tenerife
country: Spain
facility: Universidad de La Laguna
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
References: