Oral Immunotherapy in Cow's Milk Allergy (CMA) in Children : "Petit Lait" Study
Condition: Cow's Milk Allergy
MeSH terms: Hypersensitivity; Milk Hypersensitivity
Study type: Interventional

Summary: 
      Prospective study Main objective: to evaluate the efficiency and the security of two
      protocols of immunotherapy (raw milk versus heated milk) in a cohort of children with
      persistent Immunoglobulin E (IgE) mediated CMA (IgE-CMA).

      Secondary objectives: to determinate if the enumeration of casein-specific IL-4- and
      IL-13-secreting T cells could be a valuable biomarker of successful immunotherapy.
    

Detailed description: 
      The study prospectively included children aged older than 3 years, with an IgE-CMA.

      Children were part of the " Petit Lait " Study, led from June 2012 in the Allergology
      Department of Armand Trousseau Children's Hospital, "Assistance Publique-Hôpitaux de Paris
      (AP-HP)", France

        1. Inclusion criteria All the children presenting with a diagnosis of IgE- CMA(defined as a
           history of reaction to the ingestion of cow's milk product and positive skin prick test
           (wheal ≥3 mm to cow's milk with no reaction to the negative control and specific IgE to
           casein >0.35 (kiloUnit) kU/l) and referred to one of the Allergology Department were
           offered to enter the study.

           Double-blind, placebo-controlled (DBPCFC) oral food challenge The DBPCFC was performed
           outside of episodes of exacerbation of acute illness. Children were admitted to the
           allergy clinic on two separate days, and food challenges were performed under the
           supervision of an experienced allergist. A peripheral intravenous line was inserted in
           each patient before starting the challenge, according to recommendations.Increasing
           doses of cow's milk were administered 20 min apart. Two protocols were available, one
           called " standard protocol " and one called "hyperallergic protocol". Type of protocol
           was chosen before inclusion through a multidisciplinar and collegial manner. Challenge
           was stopped in case of a clinical reaction compatible with an allergic reaction.
           Antihistamine, methylprednisolone, bronchodilator or epinephrine was administered if
           necessary. Cumulative dose of cow's milk tolerated defined the reactive threshold in CMA
           children.

        2. Exclusion criteria Children who have presented an anaphylactic reaction during the
           previously year, who reacted with placebo during the DBPCFC or those with lacking
           consent or parents having difficulties to understand the protocol were excluded from the
           study.

        3. Oral Immunotherapy Phase Children were assigned by randomization to raw milk
           immunotherapy or heated milk immunotherapy.

        4. Prospective follow-up A monthly call was performed by a medical staff trained to
           allergology and families were asked on milk dose daily ingested at home and on eventual
           adverse side effects. A final DBPCFC using the standard protocol was planned once the
           daily dose attained 80 mL of raw milk.

        5. Biological markers

             -  Measurement of IgE and Immunoglobulin G4 (IgG4) against casein

             -  Measurement of Interleukin 4 (IL4) and Interleukin 13 (IL13) secreting lymphocyts
                by an Enzym Link ImmunoSpot (ELISpot) assay to cow's milk protein
    

Intervention name(s): raw milk; Heated milk
Intervention type(s): Other; Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment