Clinical trial NCT06652698: Early Supplementation for Cow's Milk Allergy Prevention
Official title: Early Supplementation for Cow's Milk Allergy Prevention in Breastfed Infants in Poland (ESCAPE-PL): a Protocol for Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Food Allergy
Cow's Milk Allergy
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
Collaborators: name: Medical Research Agency, Poland
First posted: 2024-10-22
Enrollment: 1000
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Cow's milk allergy (CMA) is a common food allergy in infants and young children that can have a significant impact on the individual and their family due to dietary restrictions, risk of nutritional deficiencies, social limitations, and decreased quality of life. It also represents a financial burden for families and healthcare resources.

There is an ongoing debate about the significance of early exposure to cow's milk proteins within hours or days after birth and its relationship to the risk of developing CMA later in life. Current recommendations for early introduction of cow's milk proteins in infants who cannot be breastfed vary and are inconsistent due to a lack of clear evidence. This knowledge gap underscores the need for further research to provide a definitive understanding of the relationship between early exposure to cow's milk proteins and the development of CMA, which will ultimately inform evidence-based prevention strategies to improve the health and well-being of affected individuals and their families.

This trial aims to investigate whether early supplementation with various nutritional interventions (cow's milk formula \[CMF\], amino acids formula \[AAF\], donor human milk \[DHM\], or high-pressure processed "pascalized" donor human milk \[DHM-P\]) could serve as an effective strategy for the primary prevention of CMA in breastfed neonates.

This study is an open-label randomized, controlled, head-to-head trial with four parallel arms and allocation 1:1:1:1.


Eligibility criteria: Inclusion criteria:

1. Healthy newborns of mothers who express the intention to exclusively breastfeed for first 6 months of infant's life
2. Full-term infants (defined as gestational age of at least 37 weeks)
3. Infant birth weight at least 2500 g and ≤ 4500 g
4. Age at enrolment \<24 h of life
5. Regardless of any atopic condition in parents
6. Written informed consent of the caregiver

Exclusion criteria:

1. Infants of parents who intend to partially or fully formula feed
2. Serious congenital anomalies or any other medical condition that would preclude the consumption of any of the study formulas, or interfere with nutrition or growth
3. Contradictions to exclusive breastfeeding
4. Multiple pregnancy

Primary outcomes:
measure: A cumulative incidence of cow's milk allergy confirmed by open oral food challenge
timeFrame: At 4-6 and 12 months of age
Secondary outcomes:
measure: A cumulative incidence of sensitization to cow's milk protein (cut-off levels for specific IgE level ≥0.35 allergen units [UA/mL] and ≥3 mm of wheal size in the skin prick test against cow's milk
timeFrame: at 6 and 12 months of age
measure: A point prevalence of cow's milk allergy confirmed by open oral food challenge
timeFrame: at 4-6, and 12 months of age
measure: An incidence of sensitization to cow's milk protein (cut-off levels for specific IgE level ≥0.35 allergen units [UA/mL] against cow's milk)
timeFrame: at 4-6, and 12 months of age
measure: In a subgroup of children with confirmed cow's milk allergy, the percentage of children with tolerance acquisition to cow's milk
timeFrame: at 9 and/or 12 months
measure: Percentage of children who received a full 3-day nutritional supplementation (3x10 ml according to the randomization) and then were exclusively or predominantly breastfed until 4 months of age
timeFrame: Up to 4 month of age
measure: A total score in the Cow's Milk-related Symptom Score (CoMiSS)
timeFrame: at 4-6 and 12 months of age
measure: Percentage of children exclusively breastfed
timeFrame: at 4 and 6 months of age
measure: Percentage of children with mixed feeding
timeFrame: at 4 and 6 months of age
measure: Change in Body Mass Index (BMI)-for-age z-score
timeFrame: at 4, 6 and 12 months of age
measure: Change in length-for-age z-score
timeFrame: at 4, 6 and 12 months of age
measure: Adverse events related to the nutritional intervention (according to the randomization)
timeFrame: up to 12 months of age
measure: A cumulative incidence of atopic dermatitis (defined as meeting the UK Working Party diagnostic Criteria)
timeFrame: at 6 and 12 months of age
measure: A cumulative incidence of allergic rhinitis (confirmed by study physician)
timeFrame: at 6 and 12 months of age
measure: A cumulative incidence of feeding difficulties who will be screened with The Montreal Children's Hospital Feeding Scale (MCH-FS scale)
timeFrame: at 6 and 12 months of age
measure: Human milk energy value (kcal/100 mL)
timeFrame: at 4-14 days postpartum and 6 months of age
measure: Total and true protein concentrations in human milk samples (g/100 mL)
timeFrame: at 4-14 days postpartum and 6 months of age
measure: Fat concentration in human milk samples (g/100 mL)
timeFrame: at 4-14 days postpartum and 6 months of age
measure: Lactose concentration in human milk samples (g/100 mL)
timeFrame: at 4-14 days postpartum and 6 months of age
measure: Dry mass content g/100 mL
timeFrame: at 4-14 days postpartum and 6 months of age
measure: IgA-anty CMA concentration in human milk samples (pg/mL)
timeFrame: at 4-14 days postpartum
measure: IL-1B, IL-6, IL-10, and TGF-beta concentrations in human milk samples (pg/mL)
timeFrame: at 4-14 days postpartum
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Medical University of Warsaw
state: Masovian
Study officials:
affiliation: Medical University of Warsaw
name: Andrea Horvath, Assoc Prof, MD
role: STUDY_CHAIR
affiliation: Medical University of Warsaw
name: Aleksandra Wesołowska, Assoc Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of Warsaw
name: Hanna Szajewska, Prof, MD
role: PRINCIPAL_INVESTIGATOR
References: