Systems Pharmacology Approach to Uncontrolled Pediatric Asthma

NCT04865575 | Completed

• 1 other identifier: NL55788.041.15
• Study Type: observational
• Target: 145
• Locations: 5 countries
• Sites: 6

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.

Conditions

Pediatric Asthma; Uncontrolled Asthma

Keywords

Systems Pharmacology; Omics

Outcome Measures

Primary Outcomes (2)

• Saliva and stool microbiome

  Differences in 16S rRNA microbial α- and ß- diversities between cases and controls

  Baseline

• Exhaled breath metabolome

  Differences in presence and levels of volatile organic compounds between cases and controls

  Baseline

Other Outcomes (10)

• Age

  Baseline (+ follow-up at 6 and 12 months after baseline inclusion)

• Sex

  Baseline (+ follow-up at 6 and 12 months after baseline inclusion)

• BMI

  Baseline (+ follow-up at 6 and 12 months after baseline inclusion)

Study Arms (2)

controlled asthmatics

moderate-to-severe asthmatic children with good asthma control

uncontrolled asthmatics

moderate-to-severe asthmatic children with poor asthma control / recurrent exacerbations

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• University of Maribor, Maribor, Slovenia.: collaborator
• University Children's Hospital, University of Regensburg, Regensburg, Germany: collaborator
• Universidad de La Laguna, San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.: collaborator
• University of the Basque Country (UPV/EHU): collaborator
• Hospital Universitario Donostia, San Sebastián, Spain.: collaborator
• Instituto de Salud Carlos III: collaborator
• Utrecht University, Utrecht, the Netherlands.: collaborator
• Karolinska Institutet: collaborator

Study Sites (6)

University Regensburg

Regensburg, Germany

Location

Utrecht University

Utrecht, Netherlands

Location

University of Maribor

Maribor, Slovenia

Location

University of the Basque Country

San Sebastián, Spain

Location

Universidad de La Laguna

Santa Cruz de Tenerife, Spain

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood, feces, saliva, nasal swabs and exhaled breath.

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 21, 2021
• First Posted: April 29, 2021
• Study Start: January 12, 2018
• Primary Completion: October 31, 2019
• Study Completion: October 31, 2020
• Last Updated: April 29, 2021

Record last verified: 2021-04

Locations

SL (1); SE (1); NL (1); DE (1); ES (2)