Pediatric Arm of DZL All Age Asthma Cohort

NCT ID: NCT02496468

Last Updated: 2024-08-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-01-31

Study Completion Date

2027-12-31

Brief Summary

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Despite its common occurrence, still little is known about pathomechanisms determining different wheeze and asthma trajectories and phenotypes in children, and those beginning in adulthood. Therefore, deciphering underlying determinants for different childhood and adult asthma phenotypes is urgently needed to develop personalized treatment approaches targeting distinct underlying mechanisms. Thereby, secondary prevention early in the disease process can also be achieved. The decoding of such mechanisms and their translation to the individual patient is the aim of the Disease Area Asthma Allergy of the 'German Centre for Lung Research' (DZL).

Detailed Description

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About 25-30% of children have at least one episode of wheeze before their 3rd birthday, but considerable clinical heterogeneity exists. Many of these children become symptom-free between 3 and 8 years of age, but some go on to persistent asthma in later childhood and adulthood. Despite its high prevalence, still little is known about pathomechanisms determining the different wheeze trajectories and phenotypes in children, and those beginning in adulthood. Frequency and severity of exacerbations may play an important role in the chronification process but underlying mechanisms are equally not well understood. Therefore, deciphering the role of airway mechanics, genetic, environmental and molecular determinants for different childhood and adult asthma phenotypes for exacerbations and chronification processes is urgently needed to develop personalized treatment approaches targeting distinct underlying mechanisms. Thereby, secondary prevention early in the disease process can also be achieved.

In order to do so, a clinical cohort for childhood asthma has been set up with identical, standardized instruments (quality assurance plan: standard operating procedures (SOPs) for clinical and lab modules, shipment, biobanking and analysis as well as quality control measures via audits and site visits have been developed) across the participating 'German Center for Lung Research' (DZL) sites. Here, new-onset steroid/leukotriene receptor antagonist (LTRA) naïve wheeze/asthma patients and wheeze/asthma patients under controller therapy are being recruited in addition to healthy controls. Following recruitment, regularly follow-ups and exacerbation visits of included patients are being performed with identical study instruments and meticulous quality control checks as at baseline.

PROJECT HYPOTHESES:

1. Specific molecular phenotypes are associated with distinct wheeze/asthma phenotypes and trajectories. Thereby, underlying mechanisms as well as predictors and biomarkers for persistent asthma will be identified.
2. Individuals at risk for exacerbations can be identified by clinical and molecular biomarkers, which will become novel targets for therapy and secondary prevention.

WORK PROGRAM:

Identification of molecular phenotypes, predictors and biomarkers for distinct wheeze/asthma phenotypes and trajectories.

The investigators aim to recruit over 1000 cases and controls to ensure sufficient statistical power for multivariate statistical analyses. Recruitment of study participants will be continued and cases will undergo 'deep phenotyping' as described below. In addition, healthy age and sex matched controls will be recruited. Cases and controls undergo a comprehensive clinical assessment including questionnaires (browser-based online data entry into extensive database with audit trail, plausibility and quality control checks implemented, data dictionary accessible), physical examination and lung function tests (spirometry and bodyplethysmography including bronchodilator response, multiple breath washout, exhaled nitric oxide). Biomaterials will be collected for analyses: i) blood samples; ii) nasal secretions; iii) pharyngeal swabs; iv) induced sputum; v) stool samples. Furthermore, epithelial cells will be collected by nasal brushings. Breath samples will be collected for analyses of volatile organic compounds. The cases will be followed up regularly using the same clinical tools and collecting the same biomaterials as at the initial visit to assess trajectories over time. Two closely interacting working groups have been established for all aims described: one lab and one data management/analysis group, each headed by expert members of the participating sites. The lab group will initiate and supervise all measurements of biomaterials; the data management/analysis group will expand the combined and shared data base and coordinate statistical analyses across sites. A common publication policy has already been developed. Using advanced bioinformatics, systems biology and machine learning approaches, the investigators will develop predictive (diagnostic) algorithms including clinical and molecular biomarkers for transient and persistent wheeze/asthma phenotypes and their trajectories. These analyses will also identify underlying mechanisms and thereby potential targets for future personalized therapy comparing childhood and adult findings. During data collection. The investigators attempt to minimize missing data. In all cases where missing data will reduce power for subsequent analyses, imputation will be used in order to omit power loss.

Conditions

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Asthma Wheeze Hypersensitivity Endophenotype

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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new-onset wheeze/asthma

children with inhaled or systemic corticosteroid-/leukotriene receptor antagonist-naïve wheeze/asthma, will undergo follow-up after initial recruitment

No interventions assigned to this group

wheeze/asthma under controller therapy

children with wheeze/asthma, already under controller (inhaled or systemic corticosteroids or leukotriene receptor antagonist) therapy, will undergo follow-up after initial recruitment

No interventions assigned to this group

healthy controls

healthy age- and sex-matched controls, will not undergo follow-up after initial recruitment

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* informed consent by parents (and by children if age \> 8 years)
* age 6 months to 18 years
* term delivery (≥ 37 weeks)
* active/passive understanding of German
* age 6 months - \< 6 years: preschool wheeze (more than two episodes of wheeze during 12 months prior to inclusion)
* age at least 6 years: doctor diagnosed asthma (according to current guidelines)

Exclusion Criteria

* known inborn or perinatal pulmonary disease
* airway malformation
* oxygen therapy after birth with a duration of more than 24 hours
* ventilator support or mechanical ventilation after birth
* diagnoses of cystic fibrosis; primary ciliary dyskinesia
* heart failure diagnosed after birth affecting pulmonary circulation
* major respiratory diseases such as e.g. interstitial lung disease
* any current non-atopic comorbidity
* fever of at least 38.5°C during the last two weeks prior to the planned first visit
Minimum Eligible Age

6 Months

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role collaborator

German Center for Lung Research

OTHER

Sponsor Role collaborator

Comprehensive Pulmonary Center Munich

UNKNOWN

Sponsor Role collaborator

Airway Research Center North

UNKNOWN

Sponsor Role collaborator

Biomedical Research in Endstage and Obstructive Lung Disease Hannover

UNKNOWN

Sponsor Role collaborator

Translational Lung Research Center Heidelberg

UNKNOWN

Sponsor Role collaborator

Universities of Giessen and Marburg Lung Center

UNKNOWN

Sponsor Role collaborator

LMU Klinikum

OTHER

Sponsor Role lead

Responsible Party

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Erika von Mutius

Prof. Dr. Bianca Schaub

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Bianca Schaub, MD

Role: PRINCIPAL_INVESTIGATOR

Klinikum der Universitaet Muenchen, Comprehensive Pulmonary Center Munich

Gesine Hansen, MD

Role: PRINCIPAL_INVESTIGATOR

Biomedical Research in Endstage and Obstructive Lung Disease Hannover

Folke Brinkmann, MD

Role: PRINCIPAL_INVESTIGATOR

Airway Research Center North

Locations

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University Children's Hospital Cologne, Department of Paediatric Allergology and Pneumology

Cologne, , Germany

Site Status RECRUITING

Medizinische Hochschule Hannover, Biomedical Research in Endstage and Obstructive Lung Disease

Hanover, , Germany

Site Status RECRUITING

Universitaetsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin, Airway Research Center North

Lübeck, , Germany

Site Status RECRUITING

Klinik für Kinder- und Jugendmedizin, Universitaetsklinikum Giessen und Marburg GmbH, Universities of Giessen and Marburg Lung Center

Marburg, , Germany

Site Status RECRUITING

Klinikum der Universitaet Muenchen, Comprehensive Pulmonary Center Munich

Munich, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Esther Zeitlmann, Diplom

Role: CONTACT

+49894400 ext. 57787

Bianca Schaub, MD

Role: CONTACT

+49894400 ext. 57897

Facility Contacts

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Silke van Koningsbruggen-Rietschel, MD

Role: primary

+49 221 478- ext. 3798

Silke van Koningsbruggen-Rietschel, MD

Role: backup

0221-478 ext. 3798

Gesine Hansen, MD

Role: primary

++49511532 ext. 9138

Anna-Maria Dittrich, MD

Role: backup

++49511532 ext. 9138

Folke Brinkmann, MD

Role: primary

++49451500 ext. 2550

Markus Weckmann, PhD

Role: backup

++49451500 ext. 2550

Stefanie Weber, PD

Role: primary

+4964215866 ext. 651

Markus Ege, MD

Role: primary

+49894400 ext. 57709

Bianca Schaub, MD

Role: backup

+49894400 ext. 57897

References

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Jakwerth CA, Weckmann M, Illi S, Charles H, Zissler UM, Oelsner M, Guerth F, Omony J, Nemani SSP, Grychtol R, Dittrich AM, Skevaki C, Foth S, Weber S, Alejandre Alcazar MA, van Koningsbruggen-Rietschel S, Brock R, Blau S, Hansen G, Bahmer T, Rabe KF, Brinkmann F, Kopp MV, Chaker AM, Schaub B, von Mutius E, Schmidt-Weber CB; ALLIANCE Study Group as part of the German Center for Lung Research. 17q21 Variants Disturb Mucosal Host Defense in Childhood Asthma. Am J Respir Crit Care Med. 2024 Apr 15;209(8):947-959. doi: 10.1164/rccm.202305-0934OC.

Reference Type DERIVED
PMID: 38064241 (View on PubMed)

Shahrokny P, Maison N, Riemann L, Ehrmann M, DeLuca D, Schuchardt S, Thiele D, Weckmann M, Dittrich AM, Schaub B, Brinkmann F, Hansen G, Kopp MV, von Mutius E, Rabe KF, Bahmer T, Hohlfeld JM, Grychtol R, Holz O. Increased breath naphthalene in children with asthma and wheeze of the All Age Asthma Cohort (ALLIANCE). J Breath Res. 2023 Oct 12;18(1). doi: 10.1088/1752-7163/acf23e.

Reference Type DERIVED
PMID: 37604132 (View on PubMed)

Maison N, Omony J, Illi S, Thiele D, Skevaki C, Dittrich AM, Bahmer T, Rabe KF, Weckmann M, Happle C, Schaub B, Meyer M, Foth S, Rietschel E, Renz H, Hansen G, Kopp MV, von Mutius E, Grychtol R; ALLIANCE Study Group; ALLIANCE Study Group; Fuchs O, Roesler B, Welchering N, Kohistani-Greif N, Kurz J, Landgraf-Rauf K, Laubhahn K, Liebl C, Ege M, Hose A, Zeitlmann E, Berbig M, Marzi C, Schauberger C, Zissler U, Schmidt-Weber C, Ricklefs I, Diekmann G, Liboschik L, Voigt G, Sultansei L, Nissen G, Konig IR, Kirsten AM, Pedersen F, Watz H, Waschki B, Herzmann C, Abdo M, Biller H, Gaede KI, Bovermann X, Steinmetz A, Husstedt BL, Nitsche C, Veith V, Szewczyk M, Brinkmann F, Malik A, Schwerk N, Dopfer C, Price M, Jirmo AC, Habener A, DeLuca DS, Gaedcke S, Liu B, Calveron MR, Weber S, Schildberg T, van Koningsbruggen-Rietschel S, Alcazar M. T2-high asthma phenotypes across lifespan. Eur Respir J. 2022 Sep 29;60(3):2102288. doi: 10.1183/13993003.02288-2021. Print 2022 Sep.

Reference Type DERIVED
PMID: 35210326 (View on PubMed)

Weckmann M, Bahmer T, Sand JM, Rank Ronnow S, Pech M, Vermeulen C, Faiz A, Leeming DJ, Karsdal MA, Lunding L, Oliver BGG, Wegmann M, Ulrich-Merzenich G, Juergens UR, Duhn J, Laumonnier Y, Danov O, Sewald K, Zissler U, Jonker M, Konig I, Hansen G, von Mutius E, Fuchs O, Dittrich AM, Schaub B, Happle C, Rabe KF, van de Berge M, Burgess JK, Kopp MV; ALLIANCE Study Group as part of the German Centre for Lung Research (DZL). COL4A3 is degraded in allergic asthma and degradation predicts response to anti-IgE therapy. Eur Respir J. 2021 Dec 9;58(6):2003969. doi: 10.1183/13993003.03969-2020. Print 2021 Dec.

Reference Type DERIVED
PMID: 34326188 (View on PubMed)

Skevaki C, Tafo P, Eiringhaus K, Timmesfeld N, Weckmann M, Happle C, Nelson PP, Maison N, Schaub B, Ricklefs I, Fuchs O, von Mutius E, Kopp MV, Renz H, Hansen G, Dittrich AM; ALLIANCE Study Group. Allergen extract- and component-based diagnostics in children of the ALLIANCE asthma cohort. Clin Exp Allergy. 2021 Oct;51(10):1331-1345. doi: 10.1111/cea.13964. Epub 2021 Jun 26.

Reference Type DERIVED
PMID: 34128558 (View on PubMed)

Fuchs O, Bahmer T, Weckmann M, Dittrich AM, Schaub B, Rosler B, Happle C, Brinkmann F, Ricklefs I, Konig IR, Watz H, Rabe KF, Kopp MV, Hansen G, von Mutius E; ALLIANCE Study Group as part of the German Centre for Lung Research (DZL). The all age asthma cohort (ALLIANCE) - from early beginnings to chronic disease: a longitudinal cohort study. BMC Pulm Med. 2018 Aug 20;18(1):140. doi: 10.1186/s12890-018-0705-6.

Reference Type DERIVED
PMID: 30126401 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://www.dzl.de/index.php/en/

Click here for more information about the German Center for Lung Research (DZL)

http://www.dzl.de/index.php/en/research/disease-areas/asthma-and-allergy

Click here for more information about the Disease Area Asthma and Allergy (DA AA) as part of the German Center for Lung Research (DZL)

Other Identifiers

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DZL_DA_AA-1

Identifier Type: -

Identifier Source: org_study_id

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