Clinical trial NCT03466931: Efficacy of the "Milk Ladder" Intervention in the Development of Tolerance and the Recognition of B Cell Epitopes in Babies Who Are Allergic to Cow's Milk Proteins
Official title: Efficacy of the "Milk Ladder" Intervention in the Development of Tolerance and the Recognition of B Cell Epitopes in Babies Who Are Allergic to Cow's Milk Proteins
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: IgE-mediated Milk Allergy
Lead sponsor: Hospital San Carlos, Madrid
Sponsor class: OTHER
First posted: 2018-03-15
Enrollment: 114
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Food allergies have become a relevant health problem in westernized societies, particularly, with children. Cow's milk (CM), along with hen's eggs, are the most common foods eliciting allergic reactions in children under 4 years of age. The main objective of this intervention study is to evaluate the safety and efficacy of the intervention known as "The Milk Ladder" in the development of tolerance by children with CM allergies. This will be compared to an historical cohort (CoALE), which investigated the natural history of this allergy. Additionally, the ability of informative epitopes will be evaluated for their potential to predict tolerance and their correlation against clinical variables.

The "Milk Ladder" will be evaluated within a prospective cohort of CM allergic children. This intervention is enacted through the introduction of meals cooked with progressively increasing amounts of cow's milk into the participant's diet. The primary outcome will be the development of tolerance which will be evaluated through a double-blind placebo-controlled food challenge. IgE and IgG4 epitopes will be described using a peptide microarray immunoassay. Quality of life will be determined by administering the FAQLQ-PF disease-specific questionnaire. Finally, within a subgroup of study participants, the ability of different peptides to activate basophils will be analyzed, and CM T cell epitopes will be studied by means of T-cell proliferation and cytokine production assays.


Eligibility criteria: Inclusion Criteria:

* Babies of both sexes.
* Age \< 12 months.
* Clinical history of immediate reaction (\<2 hours) after the intake of baby's formula and/or foods containing cow's milk.
* Sensitization to cow's milk proteins demonstrated by:

  * sIgE to cow's milk, alpha-Lactoabumin, beta-Lactoglobulin and/or Casein \>0.1KU/l (ImmunoCAP®, ThemoFisher) and/or
  * Skin prick test to cow's milk, alpha-Lactoabumin, beta-Lactoglobulin and/or Casein ≥3mm
* If the reaction to milk occurred over 3 months before the recruitment, it will be mandatory to confirm reactivity to milk with an oral food test.
* Parents / legal representatives of the participant voluntary accept to participate.

Exclusion Criteria:

* Delayed reactions (\> 2 h) after milk intake.
* Contact urticaria to milk if ingestion is well tolerated.
* Previous participation in oral tolerance induction/desensitization protocols.
* Treatment with any medication that might interfere the evaluation of the primary outcome or any study procedure.
* Any disease or condition which presents a contraindication to perform an oral challenge, either open or double-blind or any other study procedure.
* Social circumstances that might interfere with protocol adherence.
* Egg and/or wheat allergy (this exclusion criterion shall be verified before the beginning of the intervention).

Primary outcomes:
measure: Number of participants that develop tolerance to milk after the 'Milk Ladder' intervention
timeFrame: 12 months
measure: Number of participants experiencing any adverse reaction
timeFrame: 12 months
measure: Change in antigen-specific IgE and IgG4 epitopes repertoire
timeFrame: 6 and 18 months
Secondary outcomes:
measure: Quality of life
timeFrame: 6 and 18 months
measure: Potential T-cell epitopes
timeFrame: 12 months
measure: Ability of the milk allergenic peptides to activate basophils
timeFrame: 12 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
Study officials:
affiliation: Hospital Clinico San Carlos
name: Inmaculada Cerecedo, e: MD, PhD
role: STUDY_CHAIR
References: