Trial document





This trial has been registered retrospectively.
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  DRKS00015738

Trial Description

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Title

Towards the understanding of regulatory networks influencing the exacerbation of wheeze and Asthma.

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Trial Acronym

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URL of the Trial

https://www.helios-gesundheit.de/kliniken/wuppertal/

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Brief Summary in Lay Language

For several years we have been observing a worldwide increase of asthma and allergic disorders in childhood. Asthma is one of the most common diseases in childhood with an incidence of around 10%. There are currently around 300 million people worldwide suffering from asthma. The diagnosis of bronchial asthma is guideline-oriented on the basis of lung function examinations from the age of 6 years; children under the age of 6 years with typical respiratory symptoms particularly “asthmatic symptoms” (e.g. frequent obstructive bronchitis episodes) are classified as so-called "wheezers".

The earlier stages of asthma development can be observed as early as in toddlerhood. About 30-40% of all children undergo at least one obstructive bronchitis episode in their lifetime. Although most of these children lose their symptoms later in life (mostly at school enrollment), but some children still suffer from asthmatic symptoms and eventually an asthma manifest. Therefor, we established The German Pediatric Exacerbation Study Network Group.

Bronchial asthma is a heterogenous disease that can be associated with acute exacerbations and often seasonally. Depending on the underlying appearance, the severity of the disease and the inflammatory activity in the respiratory tract, this can lead to frequent obstructive bronchitis episodes / asthma attacks. The goal of the therapy is to minimize symptoms, to achieve optimal lung function and to prevent exacerbations in order to improve the quality of life of children and adolescents.

Due to this rather heterogeneous clinical picture, different molecular mechanisms are usually present. The aim of this study is to understand these molecular mechanisms during an obstructive bronchitis episode / asthma attack and to find out the differences and similarities between the two disease groups in order to sustainably improve the quality of life of those affected in the context of personalized diagnostics and therapy.

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Brief Summary in Scientific Language

The main focus of our clinical and experimental work is to describe new pheno- and endotypes, to characterize (detect) (new) signaling cascades, to evaluate developed biomarkers and to identify new biomarkers, to reveal the functions of cells and to define the role of pathogens (bacteria, viruses, fungi) during an exacerbation episode in childhood. Differentiated molecular biological and immunological methods will be used. The importance of biological libraries (e.g. “Omics-Science”) will be analyzed with clinical item parameters and their clinical significance will be highlighted in the context of multivariate analyzes of "big data" in order to find approaches for any unresolved questions still currently presenting in literature and to define new hypotheses.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00015738
  •   2018/10/31
  •   [---]*
  •   yes
  •   Approved
  •   158/2017, Ethik-Kommission der Universität Witten/Herdecke
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Secondary IDs

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Health Condition or Problem studied

  •   J45.0 -  Predominantly allergic asthma
  •   J45.1 -  Nonallergic asthma
  •   J45.8 -  Mixed asthma
  •   J45.9 -  Asthma, unspecified
  •   J20.9 -  Acute bronchitis, unspecified
  •   J40 -  Bronchitis, not specified as acute or chronic
  •   J42 -  Unspecified chronic bronchitis
  •   J20 -  Acute bronchitis
  •   J44 -  Other chronic obstructive pulmonary disease
  •   J41.0 -  Simple chronic bronchitis
  •   J41.1 -  Mucopurulent chronic bronchitis
  •   J41.8 -  Mixed simple and mucopurulent chronic bronchitis
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Interventions/Observational Groups

  •   Patients with asthma (AB) and wheeze / chronic bronchitis:

    Exacerbated patients with AB and Wheeze / chronic bronchitis who are registered at the Children’s Hospital, Helios University Medical Center Wuppertal, Witten/Herdecke University (HUKW) or Pediatric and Adolescent Medicine, Pediatric Neurology, Helios Clinic Niederberg (HKN) (academic teaching hospital of the university Duisburg / Essen) due to shortness of breath, increasing cough (respiratory tract infection), wheezing-like symptoms (including whistling, wheezing, wheezing, etc.) and acute respiratory deterioration, will, after extensive information about the exacerbation study, receive consent and the subsequent test of suitability, included in the study. The study program and the clarification are carried out by the (deputy) head of each individual test center. A separate study course is / is carried out with the medical colleagues from the children's clinic of the HUKW or HKN and a corresponding training log is kept. In cooperation with the attending doctor, the emergency clinical treatment of the patient during his acute symptoms / exacerbation is carried out. The indication for blood sampling and / or peripheral venous access system (PVK) for diagnostic and therapeutic purposes (for example, diagnostic blood sampling, administration of intravenous medication, parenteral fluid substitution, etc.) usually occurs in this phase. During the blood collection / PVK system, the additional filling of the blood tubes (maximum 4 - 7.2 milliliters, in infants (<1 year of age the maximum blood volume of 4.8 milliliters must be observed), the carrying out of the airway epithelial swabs and nasal brushing as well as the Collection of sputum.
    Depending on the clinical stabilization or improvement in the course and depending on the level of cooperation, a lung function test is attempted (spirometry / body plethysmography). The medical history and the clinical examination are carried out during the clinical stay by the attending doctor and / or (deputy) study director.
    The lung function examination is carried out either by a nurse, a doctoral candidate or by the head / deputy head.

    1. Follow-up visit
    In order to better understanding the course of an exacerbation, a telephone consultation with the parents takes place 14 to 28 days after admission to inquire about the general condition of the patient post-in-patient. If there is a corresponding pathological abnormality and / or acute illness and / or other health warning signals that could endanger the health of the child, the patient becomes a pediatrician for co-assessment / care by the pediatrician. The telephone visit is carried out by the (deputy) director or the doctoral candidate in supervision by the (deputy) director.

    2. Follow-up visit
    28 days to 3 months after the initial complaint, the patient is invited to HUKW or HKN for follow-up. Here, questionnaires are filled out with the parents, a physical examination, a lung function examination and a new biomaterial collection as in the baseline visit. The visit is carried out by the head / deputy head accompanied by a doctoral student. The follow-up visit should be made to evaluate the clinical course for comparison so that the results during the baseline visit can be compared after 28 days to 3 months. A new biomaterial collection takes place here. To minimize the puncture pain during the blood collection, appropriate pain / anesthetic plasters (e.g. 20-30 minutes can be applied to the respective puncture site). The lung function examination is carried out either by a nurse, a doctoral candidate or by the head / deputy head.


    Healthy control cohort:

    Healthy pediatric individuals from the age of 3 months to <18 years of age or healthy adult individuals> 18. to <65. Years of age who volunteer at HUKW or HKN to take part in the exacerbation study will be included in the study after detailed information about the exacerbation study, receipt of consent and the subsequent suitability test. Healthy children who are already in our children's clinic for other indications (e.g. condition after syncope, headache for clarification, head bruises etc. and a chronic organic cause cannot be proven) are also characterized as healthy individuals and asked about the study admission and afterwards Education and consent included in the study.
    Questionnaires are answered, a clinical examination and, depending on the child's cooperation, a lung function examination and a biomaterial collection.
    The director / deputy director carries out the study, the education, the physical examination as well as the biomaterial collection for children abroad. Children who are already in HUKW or HKN have already been physically examined by the receiving doctor. In order to minimize the puncture pain during the blood collection, appropriate pain / anesthetic plasters can be applied to the respective puncture site.
    For patients who are already in HUKW or HKN and already have a PVK system, the biomaterials are collected (blood, (maximum 4 - 7.2 milliliters, in infants (<1 year of life) the maximum blood volume is 4.8 milliliters If this is unsuccessful, a separate blood sample is taken, in which case appropriate pain / anesthetic plasters can be applied to the puncture site beforehand in order to minimize the puncture pain. The lung function examination is carried out either by a nurse, a doctoral candidate or by the head / deputy head. The follow-up visits in this cohort are omitted.

    Possible complications during a study visit

    The above-mentioned biomaterials and the lung function examinations are taken or carried out for diagnostic purposes as part of the routine examination. In addition, only the blood volume (maximum 4 - 7.2 milliliters; in infants under the age of 1 the maximum blood volume of 4.8 milliliters must be observed) and the nasal brushing for the study. There is no additional risk for patients from whom blood is to be drawn for diagnostic purposes anyway, since a small amount of blood is sufficient here, which can be drawn or additionally dispensed as part of the routine procedure. The usual risks of drawing blood apply to patients who need additional blood. Basically, the medical risk associated with peripheral venous blood sampling is negligible. In very rare cases, circulatory problems, infection, thrombosis or damage to neighboring tissues and nerves by the blood sampling needle can occur. These are extremely rare with one-time blood sampling as in this case and practically impossible with trained personnel. Nasal throat swabs / nasal brushing can occasionally lead to sneezing and slight nosebleeds due to skin soft tissue nerve injuries.
    The pulmonary function examination is a non-invasive method in which the patient inhales and exhales volumes (forced and at rest) through inspiration and expiration. These values give the pediatrician information about the current lung condition and play a major role in deciding on the further course of therapy. Since the examination is non-invasive, there are usually no side effects / complications. In rare cases, however, repeated inhalation and expiration maneuvers can lead to symptoms of typical hyperventilation (e.g. headaches, tingling sensations on the extremities, a shift in the electrolyte balance, and even impaired consciousness). In such a case, inhalation and exhalation in a plastic bag would be therapeutically indicated.
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Basic research/physiological study
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Clinical course 3 month after exacerbation; comparison of experimental parameters/results between acute exacerbation and clinically healthy condition

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Secondary Outcome

none

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • Medical Center 
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Recruitment

  •   Actual
  •   2017/12/01
  •   300
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   3   Months
  •   65   Years
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Additional Inclusion Criteria

Asthma cohort:
• Patients with asthma ≥ 5.-6. to <18 years of age
• Patients with undeclared asthma but recurrent obstructive bronchitis episodes prior to 5-6. Years of age and with current symptoms of infection, obstructive bronchitis episode, respiratory deterioration or tachy-dyspnea.

Diagnosis of asthma based on objective criteria:
• Pulmonary obstruction (FEV1 / VC <80%)
• Positive bronchospasmolysis (FEV1 / VC> 12%)
• Positive increase of FEV1 / VC> 12% after inhaled steroid therapy> 4 weeks
• FEV1 / VC increase> 10% after treadmill load (bronchial hyperresponsiveness)
• Positive methacholine provocation (decrease of FEV1 / VC> 20%)
• circadian PEF variability> 20%

Perinatal period unremarkable, delivery ≥ 37th week of gestation

No underlying diseases (no postnatal respiratory adaption disorder, no respiratory breathing aid, no machine ventilation, etc., lack of genetic / mental / physical developmental delay, no pulmonary diseases (e.g. Primary ciliary dyskinesia, cystic fibrosis, bronchopulmonary dysplasia, other lung diseases etc.)

Written consent of the patient (≥ 11th year of age) and the parents/legal guardian

Wheezer cohort:
Patients with recurrent obstructive bronchitis ≥ 3 months to ≤ 5 years / 6 years of age
• At least 2 obstructive bronchitis episodes in their life
o at least one outpatient and one inpatient treatment (the current inpatient presentation can also be considered as an episode)

No underlying diseases (no postnatal respiratory adaption disorder, no respiratory breathing aid, no machine ventilation, etc., lack of genetic / mental / physical developmental delay, no pulmonary diseases (e.g. Primary ciliary dyskinesia, cystic fibrosis, bronchopulmonary dysplasia, other lung diseases etc.)
Written consent of the parents/legal guardian

Healthy cohort:
Healthy children and adolescents between ≥ 3 months and <18 years of age

No underlying diseases (no postnatal respiratory adaption disorder, no respiratory breathing aid, no machine ventilation, etc., lack of genetic / mental / physical developmental delay, no pulmonary diseases (e.g. Primary ciliary dyskinesia, cystic fibrosis, bronchopulmonary dysplasia, other lung diseases etc.)

Written consent of the subjects (≥ 11th years of age) and the parents/legal guardian

No permanent medication
No febrile infection in the last 3 weeks


Healthy adults between the ages of ≥ 18 and <65. age

No underlying illnesses
No long-term medication
No febrile infection in the last 2 weeks
Consent of the study patient

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Exclusion Criteria

Asthma cohort:
No fulfilling of inclusion criteria
No consent of patient (≥ 11th year of age) parents/legal guardian

Wheeze cohort:

No fulfilling of inclusion criteria
No consent of parents/ legal guardian

Healthy cohort:
No fulfilling of inclusion criteria
No consent of patient (≥ 11th year of age) parents/legal Guardian
No consent of the study participants

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Addresses

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    • Zentrum für Kinder- und Jugendmedizin, Zentrum für Forschung in der Klinischen Medizin, Helios Universitätsklinikum Wuppertal, Universität Witten/Herdecke
    • Mr.  Prof. Dr.  Stefan  Wirth 
    • Heusnerstr. 40
    • 42283  Wuppertal
    • Germany
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    • Kinder- und Jugendmedizin, Kinderneurologie Helios Klinikum Niederberg – Akademisches Lehrkrankenhaus der Universität Duisburg/Essen
    • Mr.  Dr.  Sören  Lutz 
    • Robert-Koch-Straße 2
    • 42549  Velbert
    • Germany
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  • start of 1:1-Block address scientific-contact
    • Zentrum für Kinder- und JugendmedizinHelios Universitätsklinikum WuppertalUniversität Witten/Herdecke
    • Mr.  Professor Dr.  Stefan  Wirth 
    • Heusnerstr. 40
    • 42283  Wuppertal
    • Germany
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  • start of 1:1-Block address scientific-contact
    • Zentrum für Kinder- und JugendmedizinHelios Universitätsklinikum WuppertalUniversität Witten/Herdecke
    • Mr.  Malik  Aydin 
    • Heusnerstr. 40
    • 42283  Wuppertal
    • Germany
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    • Zentrum für Kinder- und JugendmedizinHelios Universitätsklinikum WuppertalUniversität Witten/Herdecke
    • Mr.  Malik  Aydin 
    • Heusnerstr. 40
    • 42283  Wuppertal
    • Germany
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    end of 1:1-Block address contact public-contact
  • start of 1:1-Block address public-contact
    • Kinder- und Jugendmedizin, Kinderneurologie Helios Klinikum Niederberg – Akademisches Lehrkrankenhaus der Universität Duisburg/Essen
    • Mr.  Dr.  Sören  Lutz 
    • Robert-Koch-Straße 2
    • 42549  Velbert
    • Germany
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Sources of Monetary or Material Support

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    • Zentrum für Kinder- und Jugendmedizin, Zentrum für Forschung in der Klinischen Medizin, Helios Universitätsklinikum Wuppertal, Universität Witten/Herdecke
    • Mr.  Prof. Dr.  Stefan  Wirth 
    • Heusnerstr. 40
    • 42283  Wuppertal
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.