Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT06652698

Early Supplementation for Cow's Milk Allergy Prevention

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Food Allergy Cow's Milk Allergy Food Hypersensitivity Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Milk Hypersensitivity

Age range

Up to 24 hour

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Medical University of Warsaw

Warsaw, Masovian Voivodeship, 02-091, Poland

Location contact

Andrea Horvath, Assoc Prof

CONTACT

[email protected]

22 317 9444

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Infants of parents who intend to partially or fully formula feed
  • 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
  • Contradictions to exclusive breastfeeding
  • Multiple pregnancy

Treatment and study plan

Cow's milk formula [CMF]

Other

At least 10 ml daily of cow's milk formula (Bebiko 1 NUTRIFlor Expert®, Nutricia; formula with galactooligosaccharides and without probiotics); and if additional supplementation will be needed (i.e., insufficient, partial, or discontinuation of breastfeeding), the randomly assigned nutritional intervention until the end of 4 months of age will be provided.

Amino-acid formula [AAF]

Other

At least 10 ml daily of amino-acid formula (Nutramigen Pureamino®, Reckitt Benckiser Group PLC); and if additional supplementation will be needed (i.e., insufficient, partial, or discontinuation of breastfeeding), the randomly assigned nutritional intervention until the end of 4 months of age will be provided.

Donor human milk [DHM]

Other

At least 10 ml daily of donor human milk; and if additional supplementation will be needed (i.e., insufficient, partial, or discontinuation of breastfeeding), the randomly assigned nutritional intervention until the end of 4 months of age will be provided.

High-pressure processed "pascalized" donor human milk [DHM-P]

Other

At least 10 ml daily of high-pressure processed "pascalized" donor human milk; and if additional supplementation will be needed (i.e., insufficient, partial, or discontinuation of breastfeeding), the randomly assigned nutritional intervention until the end of 4 months of age will be provided.

Primary outcomes

  1. A cumulative incidence of cow's milk allergy confirmed by open oral food challenge

    Time frame: At 4-6 and 12 months of age

Secondary outcomes

  1. 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

    Time frame: at 6 and 12 months of age

  2. A point prevalence of cow's milk allergy confirmed by open oral food challenge

    Time frame: at 4-6, and 12 months of age

  3. 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)

    Time frame: at 4-6, and 12 months of age

  4. In a subgroup of children with confirmed cow's milk allergy, the percentage of children with tolerance acquisition to cow's milk

    Time frame: at 9 and/or 12 months

    Tolerance acquisition to cow's milk will be assessed by subsequent OFC with baked milk (in the form of biscuit or muffin); if baked milk is tolerated, the assessment of tolerance acquisition will be continued with the use of milk ladder.

  5. 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

    Time frame: Up to 4 month of age

  6. A total score in the Cow's Milk-related Symptom Score (CoMiSS)

    Time frame: at 4-6 and 12 months of age

    The total CoMiSS score ranges from 0 to 33, a score of ≥10 indicates CMA.

  7. Percentage of children exclusively breastfed

    Time frame: at 4 and 6 months of age

  8. Percentage of children with mixed feeding

    Time frame: at 4 and 6 months of age

  9. Change in Body Mass Index (BMI)-for-age z-score

    Time frame: at 4, 6 and 12 months of age

    weight and length will be checked each month in a telephone interview or parental report, or during follow-up visit assessed by study physician; change in mean value will be assessed between baseline and each time point

  10. Change in length-for-age z-score

    Time frame: at 4, 6 and 12 months of age

    length will be checked each month in a telephone interview or parental report, or during follow-up visit assessed by study physician; change in mean value will be assessed between baseline and each time point

  11. Adverse events related to the nutritional intervention (according to the randomization)

    Time frame: up to 12 months of age

    defined as any harmful events that may occur during the trial; the process of decision whether an adverse event is related to the intervention (attribution) will be made by the non-blinded principal investigator

  12. A cumulative incidence of atopic dermatitis (defined as meeting the UK Working Party diagnostic Criteria)

    Time frame: at 6 and 12 months of age

  13. A cumulative incidence of allergic rhinitis (confirmed by study physician)

    Time frame: at 6 and 12 months of age

  14. A cumulative incidence of feeding difficulties who will be screened with The Montreal Children's Hospital Feeding Scale (MCH-FS scale)

    Time frame: at 6 and 12 months of age

    Total score range from 14 to 98, score of 46 or higher indicates feeding difficulties.

  15. Human milk energy value (kcal/100 mL)

    Time frame: at 4-14 days postpartum and 6 months of age

  16. Total and true protein concentrations in human milk samples (g/100 mL)

    Time frame: at 4-14 days postpartum and 6 months of age

  17. Fat concentration in human milk samples (g/100 mL)

    Time frame: at 4-14 days postpartum and 6 months of age

  18. Lactose concentration in human milk samples (g/100 mL)

    Time frame: at 4-14 days postpartum and 6 months of age

  19. Dry mass content g/100 mL

    Time frame: at 4-14 days postpartum and 6 months of age

  20. IgA-anty CMA concentration in human milk samples (pg/mL)

    Time frame: at 4-14 days postpartum

  21. IL-1B, IL-6, IL-10, and TGF-beta concentrations in human milk samples (pg/mL)

    Time frame: at 4-14 days postpartum

Study contacts

Contact information is provided by the study sponsor or research team.

Andrea Horvath, Assoc Prof

CONTACT

[email protected]

22 317 9444

Sponsors and collaborators

Lead sponsor

Medical University of Warsaw

Other

Collaborators

  • Medical Research Agency, Poland

Registry information

Official study title

Early Supplementation for Cow's Milk Allergy Prevention in Breastfed Infants in Poland (ESCAPE-PL): a Protocol for Randomised Controlled Trial

Acronym: ESCAPE-PL

Important dates

Study start
2025
Primary completion
2030
Study completion
2031
First posted
Oct 22, 2024
Registry last updated
Jul 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.