Trial document




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  DRKS00016770

Trial Description

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Title

Tolerance induction through early feeding to prevent food allergy in infants with eczema

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

Up to 8% of all infants and children suffer from IgE-mediated food allergy and therefore this condition is a veritable burden in industrialized countries. Our understanding of underlying immunological, environmental, genetic and epigenetic mechanisms is still limited. Especially infants with eczema are at high risk for developing food allergies, which may result in life threatening anaphylaxis. The most common foods are hen’s egg, cow’s milk, peanuts, and tree nuts. Food allergy often starts in infancy and interestingly many children become sensitized against certain foods even before eating them for the first time. According to the current understanding sensitization occurs via the cutaneous route due to an impaired skin barrier function in these infants. In addition genetic factors play an important role. The cutaneous route of sensitization is of special interest and we could show that food proteins can be found in bed dust and increase with consumption. In order to avoid anaphylactic reactions occurring at home with the first feeding, children with moderate to severe eczema are routinely screened for sensitization against the most important food allergens before these foods are introduced into the infant diet. In the past prevention strategies concerning the development of food allergy have been driven by avoidance of allergenic foods in high risk infants. Despite these attempts a rising prevalence of food allergy has been observed. Therefore current guidelines do not recommend avoidance any longer. However, the optimal strategy of allergen introduction into the infants diet is still under a heavy debate. The main questions are “when”, “how”, “which allergen” and “which children”. In order to address this question several randomized controlled studies with different food allergens have been conducted by others and us. However, many questions still require an answer before evidence based advice can be given for prevention of food allergy. Therefore, in our proposed trial, we will introduce small amounts of four highly allergenic foods (heated hen’s egg, cow’s milk, peanut and hazelnut) in parallel in one feeding along with the first weaning foods in infants with eczema at 4-6 months of age in a randomized placebo controlled trial in order to promote oral tolerance development and to understand the underlying mechanisms. With this approach we will be able to give additional answers to all relevant remaining questions in current research. With the gained knowledge we should be able to update current prevention guidelines and shed also light in the immunological mechanism of food allergy and tolerance development.

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Brief Summary in Scientific Language

Background:
Food allergies often develop within the first year of life, mainly in infants with eczema, and may result in life threatening anaphylaxis. Sensitization seems to occur via the cutaneous route caused by an impaired skin barrier. In order to prevent the onset of food allergies, especially in these children with atopic conditions, several intervention studies with different food allergens have been conducted. On the one hand, it has been shown that the frequency of peanut allergy in infants with severe eczema was reduced through early oral feeding but in contrast, early feeding with high amounts of raw hen’s egg resulted in frequent allergic reactions but did not prevent hen’s egg allergy. Another study tried a parallel prevention of food allergy through the sequential introduction of various highly allergenic foods, but due to a complicated protocol the majority of families could not be included in the intention-to-treat analysis. Therefore, a well-designed prevention trial including mechanistic approaches to offer fundamental insights in the mechanism of tolerance induction is urgently needed.

Aims:
In order to address these knowledge gaps, we aim to induce oral tolerance to hen’s egg, cow’s milk, peanut, and hazelnut in infants with eczema through early oral allergen exposure in a randomized placebo controlled study. We hypothesize that in children with eczema early feeding of these allergens while breast-feeding continues will reduce the incidence of food allergy by 70% at one year of age. In order to understand the mechanisms involved in allergy development or tolerance induction biological samples for the mechanistic projects within this clinical research unit will be obtained.

Methods:
150 Infants with eczema at age 4-6 months will be randomized (2:1) into two groups. Group A will receive cookies with small amounts of hen’s egg, cow’s milk, peanut and hazelnut once a day, whereas group B will receive allergen-free cookies in a double-blind manner until age 12 months. The primary outcome is at least one IgE-mediated food allergy to hen’s egg, cow’s milk, peanut or hazelnut at 12 months of age confirmed by an oral food challenge. Blood, stool, saliva, dust samples and skin swabs will be analysed before intervention and at 12 months.

Conclusion:
Due to inconsistent results, current research results are insufficient for evidence-based prevention advice. Therefore, this study should provide insight into the underlying pathomechanisms of food allergy and tolerance development as well as update the current prevention guidelines.

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

No

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00016770
  •   2020/01/09
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  •   yes
  •   Approved
  •   EA2/032/19, Ethik-Kommission der Charité -Universitätsmedizin Berlin-
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Secondary IDs

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Health Condition or Problem studied

  •   T78.1 -  Other adverse food reactions, not elsewhere classified
  •   L20.9 -  Atopic dermatitis, unspecified
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Interventions/Observational Groups

  •   Infants, Age 4-6 months, with eczema, receiving daily rust-like biscuits containing small amounts of hen´s egg, cow´s milk, peanut and hazelnut
  •   Infants, Age 4-6 months, with eczema, receiving daily rust-like biscuits without hen´s egg, cow´s milk, peanut and hazelnut
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist, caregiver, assessor
  •   Placebo
  •   Prevention
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Food allergy to at least on one of the following Foods: hen´s egg, cow´s milk, hazelnut and peanut at 12 months

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Secondary Outcome

1. Allergic reactions during Intervention
2. Multiple food allergies, bronchial asthma, changes in disease severity of eczema
3. Changes of the microbiome (Skin and gut), changes in immunological processes
4. Identification of genetic and epigenetic factors associated with Food allergy
5. Identification of biomarker characterizing anaphylactic reactions

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Planned
  •   2020/02/01
  •   150
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   4   Months
  •   6   Months
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Additional Inclusion Criteria

1. children, age 4-6 months
2. eczema
3. signed informed consent of parents

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Exclusion Criteria

- previous consumption of hen´s egg, cow´s milk, peanut or hazelnut
- severe diseases (cardiac, congenital)
- participation in another interventional Trial

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Addresses

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    • Charité Campus Charité Mitte
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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    • Charité Campus Charité Mitte
    • Charitéplatz 1
    • 10117  Berlin
    • Germany
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    • Max-Delbrück-Centrum für Molekulare Medizin
    • Robert-Rössle Str. 10
    • 13125  Berlin
    • Germany
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    • Berlin-Brandenburger Centrum für Regenerative Therapien
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Charité Campus Virchow-Klinikum
    • Ms.  Prof. Dr.  Kirsten  Beyer 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Charité Campus Virchow-Klinikum
    • Ms.  Prof Dr  Kirsten  Beyer 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Forschungsgemeinschaft
    • Kennedyallee 40
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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