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AsthmaALLIANCENCT02496468

Pediatric Arm of DZL All Age Asthma Cohort

An observational study of Asthma and Wheeze, run by LMU Klinikum at 5 sites in Germany.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 6 months to 18 yearsHealthy volunteers can take part
Conditions the study is for
Asthma, Wheeze, Hypersensitivity
How many people
1,500 participants
Where
5 sitesGermany
Study dates
Jan 2013to Dec 2027
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 18 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Study population: preschool children with wheeze and school children as well as adolescents with asthma

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

5 sites in 1 country

Germany5 sites, 5 recruiting
  • University Children's Hospital Cologne, Department of Paediatric Allergology and Pneumology

    Cologne, 50937

    Silke van Koningsbruggen-Rietschel, MD, +49 221 478- ext. 3798, Silke.vanKoningsbruggen@uk-koeln.de

    Silke van Koningsbruggen-Rietschel, MD, 0221-478 ext. 3798, Silke.vanKoningsbruggen@uk-koeln.de

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

    Hanover, 30625

    Gesine Hansen, MD, ++49511532 ext. 9138, Hansen.Gesine@mh-hannover.de

    Anna-Maria Dittrich, MD, ++49511532 ext. 9138, Dittrich.Anna-Maria@mh-hannover.de

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

    Lübeck, 23528

    Folke Brinkmann, MD, ++49451500 ext. 2550, folke.brinkmann@uksh.de

    Markus Weckmann, PhD, ++49451500 ext. 2550, Markus.Weckmann@uksh.dea

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

    Marburg, 35033

    Stefanie Weber, PD, +4964215866 ext. 651

    Stefanie Weber, PD

    Recruiting
  • Klinikum der Universitaet Muenchen, Comprehensive Pulmonary Center Munich

    Munich, 80337

    Markus Ege, MD, +49894400 ext. 57709, markus.ege@med.uni-muenchen.de

    Bianca Schaub, MD, +49894400 ext. 57897, bianca.schaub@med.uni-muenchen.de

    Recruiting

Other trials in Germany

About this study

Official title: The All Age Asthma Cohort (ALLIANCE) of the German Center for Lung Research (DZL), Pediatric Arm

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).

Read the detailed description

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.

Keywords
childhood asthma, preschool wheeze, adult asthma, transition, phenotype, endotype, trajectory
Medical subject headings
Asthma, Respiratory Sounds, Hypersensitivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02496468
Study groupRoleWhat they receive
new-onset wheeze/asthmachildren with inhaled or systemic corticosteroid-/leukotriene receptor antagonist-naïve wheeze/asthma, will undergo follow-up after initial recruitment
wheeze/asthma under controller therapychildren with wheeze/asthma, already under controller (inhaled or systemic corticosteroids or leukotriene receptor antagonist) therapy, will undergo follow-up after initial recruitment
healthy controlshealthy age- and sex-matched controls, will not undergo follow-up after initial recruitment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prevalence of asthma

    Study participants will be assessed with regard to their development of asthma.

    Measured: At baseline and during yearly follow-ups up to 2 years

  2. Prevalence of transient preschool wheeze

    Study participants will be assessed with regard to their development of transient preschool wheeze.

    Measured: At baseline and during yearly follow-ups up to 2 years

Secondary outcomes (4)
  1. Prevalence of atopic sensitization

    The prevalence of atopic sensitization will be measured by the detection of specific immunoglobin E against common aeroallergens.

    Measured: At baseline and during yearly follow-ups up to 2 years

  2. Lung function

    Study participants will be assessed with regard to lung function parameters (as measured by spirometry/bodyplethysmography and multiple-breath washouts (MBW)).

    Measured: At baseline and during yearly follow-ups up to 2 years

  3. Levels of exhaled nitric oxide

    Levels of exhaled nitric oxide (eNO) will be measured by chemoluminescence analyzers in combination with ultrasound-based flow measurement.

    Measured: At baseline and during yearly follow-ups up to 2 years

  4. Frequency of acute exacerbations during previous 12 months

    The frequency of acute exacerbations during previous 12 months will be assessed by questionnaires.

    Measured: At baseline and during yearly follow-ups up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2015 (estimated)
  2. Study startJan 2013
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
1,500 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02496468
Sponsor's protocol ID
DZL_DA_AA-1
Acronym
ALLIANCE
Status last verified
Aug 2024
First submitted
3 Jul 2015
Last updated
28 Aug 2024
Results posted
No
Data monitoring committee
No

Publications

  • Jakwerth CA, Illi S, Charles H, Oelsner M, Gabr AA, Zissler UM, Erb A, Feuerherd M, Drost F, Buttner M, Schubert B, Maison N, Omony J, Weckmann M, Grychtol R, Dittrich AM, Foth S, Skevaki C, Trojan T, van Koningsbruggen-Rietschel S, Hansen G, Bahmer T, Rabe KF, Brinkmann F, Kopp MV, Protzer U, Chaker AM, Schaub B, von Mutius E, Schmidt-Weber CB; ALLIANCE Study Group as part of the German Center for Lung Research (DZL). Nasal Epithelial Immune Signatures Are Associated With Age-Dependent Asthma Trajectories in Early Life. Allergy. 2026 Sep 6. doi: 10.1111/all.70477. Online ahead of print.

    PubMed 42703035
  • Lagally L, Ullemeyer L, Omony J, Gottschau K, Foppiano F, Abdo M, Veith V, Tholken C, Hose A, Maison N, Grychtol R, Dittrich AM, Riemann L, Weckmann M, Konig I, Kronziel L, Illi S, van Koningsbruggen-Rietschel S, Rabe KF, Renz H, Hansen G, Brinkmann F, Kopp MV, von Mutius E, Bahmer T, Ege M, Skevaki C, Schaub B; ALLIANCE Study Group. Increased high sensitivity C-reactive protein in more severe wheeze/asthma phenotypes in child- and adulthood in ALLIANCE. Respir Res. 2026 Jul 27;27(1):294. doi: 10.1186/s12931-026-03840-x.

    PubMed 42509549
  • 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.

    PubMed 38064241
  • 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.

    PubMed 37604132
  • 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.

    PubMed 35210326
  • 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.

    PubMed 34326188
  • 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.

    PubMed 34128558
  • 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.

    PubMed 30126401

Questions about this trial

What is this clinical trial studying?

An observational study of Asthma and Wheeze, run by LMU Klinikum at 5 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Esther Zeitlmann, Diplom (+49894400 ext. 57787, esther.zeitlmann@med.uni-muenchen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prevalence of asthma (time frame: At baseline and during yearly follow-ups up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02496468, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2024.

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