Oral Immunotherapy in Cow's Milk Allergy (CMA) in Children : "Petit Lait" Study (Petit Lait)
Primary Purpose
Cow's Milk Allergy
Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
raw milk
Heated milk
Sponsored by
About this trial
This is an interventional treatment trial for Cow's Milk Allergy
Eligibility Criteria
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 kU/l)
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
Sites / Locations
- Service d'Allergologie
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Raw milk
Heated milk
Arm Description
For raw milk immunotherapy (RMI), fixed dose of raw milk was daily administered at home, determined using tolerated threshold dose during the DBPCFC. Augmentation was made every 5 weeks in the allergy clinic.
For heated milk immunotherapy (HMI), families were asked to weekly increase the daily dose of milk at home using industrial preparations. Milk included in the preparation was less and less heated among time. Passage from heated-milk to half-heated milk and then raw milk was performed in the allergy clinic.
Outcomes
Primary Outcome Measures
Clinical Outcome: increased tolerance to cow's milk
daily unit dose in milliliters of milk ingested
Clinical Outcome: occurrence of allergic reaction to cow's milk
Number of patients with occurrence of allergic reaction; if yes, severity of allergic reaction evaluated using: Astier score; number of use of rescue medications such as: bronchodilator, anti-histaminics, systemic corticosteroids, epinephrin
Secondary Outcome Measures
Biological Outcome: kinetics of specific IgE against casein
changes in blood level of specific IgE against casein
Biological Outcome: kinetics of specific IgG4 against casein
changes in blood level of specific IgG4 against casein
Biological Outcome: kinetics of IL4 secreting lymphocytes against casein
ELISPOT assay
Biological Outcome: kinetics of IL13 secreting lymphocytes against casein
ELISPOT assay
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02465905
Brief Title
Oral Immunotherapy in Cow's Milk Allergy (CMA) in Children : "Petit Lait" Study
Acronym
Petit Lait
Official Title
Oral Immunotherapy in Cow's Milk Allergy (CMA) in Children : "Petit Lait" Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
May 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr Flore AMAT
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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
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.
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.
Oral Immunotherapy Phase Children were assigned by randomization to raw milk immunotherapy or heated milk immunotherapy.
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cow's Milk Allergy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Raw milk
Arm Type
Active Comparator
Arm Description
For raw milk immunotherapy (RMI), fixed dose of raw milk was daily administered at home, determined using tolerated threshold dose during the DBPCFC. Augmentation was made every 5 weeks in the allergy clinic.
Arm Title
Heated milk
Arm Type
Active Comparator
Arm Description
For heated milk immunotherapy (HMI), families were asked to weekly increase the daily dose of milk at home using industrial preparations. Milk included in the preparation was less and less heated among time. Passage from heated-milk to half-heated milk and then raw milk was performed in the allergy clinic.
Intervention Type
Other
Intervention Name(s)
raw milk
Intervention Type
Other
Intervention Name(s)
Heated milk
Primary Outcome Measure Information:
Title
Clinical Outcome: increased tolerance to cow's milk
Description
daily unit dose in milliliters of milk ingested
Time Frame
12 months
Title
Clinical Outcome: occurrence of allergic reaction to cow's milk
Description
Number of patients with occurrence of allergic reaction; if yes, severity of allergic reaction evaluated using: Astier score; number of use of rescue medications such as: bronchodilator, anti-histaminics, systemic corticosteroids, epinephrin
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Biological Outcome: kinetics of specific IgE against casein
Description
changes in blood level of specific IgE against casein
Time Frame
12 months
Title
Biological Outcome: kinetics of specific IgG4 against casein
Description
changes in blood level of specific IgG4 against casein
Time Frame
12 months
Title
Biological Outcome: kinetics of IL4 secreting lymphocytes against casein
Description
ELISPOT assay
Time Frame
12 months
Title
Biological Outcome: kinetics of IL13 secreting lymphocytes against casein
Description
ELISPOT assay
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 kU/l)
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
Facility Information:
Facility Name
Service d'Allergologie
City
Paris
ZIP/Postal Code
75012
Country
France
12. IPD Sharing Statement
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Oral Immunotherapy in Cow's Milk Allergy (CMA) in Children : "Petit Lait" Study
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