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

NCT03466931 | Unknown

• 1 other identifier: Milk Ladder
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

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.

Conditions

IgE-mediated Milk Allergy

Outcome Measures

Primary Outcomes (3)

• Number of participants that develop tolerance to milk after the 'Milk Ladder' intervention

  Tolerance assessment: participants who successfully pass a double-blind placebo-controlled oral food challenge without experiencing any limiting symptom

  12 months

• Number of participants experiencing any adverse reaction

  Number of participants experiencing any adverse reaction to milk-containing foods along the intervention assessed by Medical Dictionary for Regulatory Activities (MedDRA), version in place at the end of the study.

  12 months

• Change in antigen-specific IgE and IgG4 epitopes repertoire

  Serum specific inmunnoglobulin levels using a milk peptide microarray immunoassay

  6 and 18 months

Secondary Outcomes (3)

• Quality of life

  6 and 18 months

• Potential T-cell epitopes

  12 months

• Ability of the milk allergenic peptides to activate basophils

  12 months

Study Arms (2)

Dietary intervention

EXPERIMENTAL

Meals containing Milk and Milk

Other: Milk

Historical cohort

NO INTERVENTION

Standard care

Interventions

Milk OTHER

Meals containing Milk and Milk

Dietary intervention

Eligibility Criteria

• Age: 1 Month - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital San Carlos, Madrid: lead

Study Sites (1)

Hospital Clinico San Carlos

Madrid, 28040, Spain

RECRUITING

MeSH Terms

Interventions

Milk

Intervention Hierarchy (Ancestors)

Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Dairy Products; Food; Food and Beverages

Study Officials

• Inmaculada Cerecedo, e: MD, PhD

  Hospital Clinico San Carlos

  STUDY CHAIR

Central Study Contacts

Inmaculada Cerecedo, MD, PhD

CONTACT

+ 34 913303000; Inmaculada.cerecedo@salud.madrid.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 2, 2018
• First Posted: March 15, 2018
• Study Start: June 1, 2018
• Primary Completion: June 1, 2021
• Study Completion: August 30, 2021
• Last Updated: June 26, 2020

Record last verified: 2020-06

Locations

ES (1)