Investigate Effects of A2 Milk on Breastmilk Composition and Subsequent Infant Gut Health, Crying and Sleep Patterns in Healthy, Full-term Infants

A Double-blind, Parallel Designed, Randomized Controlled Trial to Investigate Effects of Conventional Vs A2 Milk on Breastmilk Composition and Subsequent Infant Gut Health, Crying and Sleep Patterns in Healthy, Full-term Infants

The goal of this interventional study is to investigate effects of a2 Full Cream Milk on Breastmilk composition and subsequent Infant gut health, crying frequency and sleep patterns in Healthy Full-term Infants.

50 mothers and thier infants will be enrolled into 2 study sites, mother and her child as one subject will be randomized to 2 groups for assigned interventions, a2 Full Cream Milk and conventional Milk (Weidendorf). The study will continue for 14 days, and 3 site visits will be made duing the study period. All data specified in the protocol will be captured and recorded into CTMS for analysis.

Researchers will compare the two groups of participants to see if a2 Full Cream Milk has significantly better breastmilk composition and improve infant's gut health, crying frequency and sleep patterns.

Study Overview

• Status: Completed
• Conditions: Sleepiness; Digestive System Disease; Crying
• Intervention / Treatment: Dietary supplement: a2 Full Cream Milk; Dietary supplement: Conventional Milk (Weidendorf)

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Jinhua, Zhejiang, China
      • Qiu Bin Community Hospital
    • Jinhua, Zhejiang, China
      • Jinhua Wenrong Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Mothers who are 25 to 45 years old;
• Mothers who are exclusively breastfeeding with healthy and full-term infants;
• Infants of these mothers who have been exclusively breastfed since birth, and their parent(s) decides to continue exclusively breastfeeding until at least 120 days of age, birth weight between 2500g and 4500g;
• Willing to sign ICF before the study launched.

Exclusion Criteria:

• Mothers with infection or have recently taken the flu / covid vaccine in the last 4 weeks;
• Infant with inborn malformation and with hereditary and/or chronic and/or inborn diseases that could interfere with the survey;
• Evidence of feeding difficulties or intolerance/allergy to cow's milk (mixed-fed group only);
• Conditions requiring infant feedings other than those specified in the protocol;
• Significant systemic disorders (cardiac, respiratory, endocrinological, hematologic, gastrointestinal, or other); or parental refusal to participate;
• Infants with an acute infection or gastroenteritis at time of enrollment;
• Participation in another clinical trial;
• Investigator's uncertainty about the willingness or ability of the parents to comply with the protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: a2 Full Cream Milk; a2 Full Cream Milk, 200ml/bag, per 100ml serving Nutrient Composition Energy: 250 kcal Protein:3.2g Fat:3.3g Carbohydrate:4.3g Sodium:40mg Calcium:104mg	Dietary supplement: a2 Full Cream Milk; Mothers in this arm will drink a2 Full Cream Milk twice a day, 200ml each time, for 14 consecutive days. Infants in this arm will be fed with mather's breastmilk exclusively.
Active Comparator: Conventional Milk (Weidendorf); Conventional Milk (Weidendorf), 200ml/bag,per 100ml serving Nutrient Composition Energy: 267 kcal Protein:3.3g Fat:3.5g Carbohydrate:4.8g Sodium:50mg Calcium:120mg	Dietary supplement: Conventional Milk (Weidendorf); Mothers in this arm will drink Conventional Milk (Weidendorf) twice a day, 200ml each time, for 14 consecutive days. Infants in this arm will be fed with mather's breastmilk exclusively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast milk excretion of Human Milk oligosaccharide content (HMO) content	Qualitative analysis of Breast milk excretion of Human Milk oligosaccharide content (HMO) content on baseline day	Baseline (T0)
Breast milk excretion of Human Milk oligosaccharide content (HMO) content	Qualitative analysis of Breast milk excretion of Human Milk oligosaccharide content (HMO) content on day 14	After 14 days of supplementation (T14)
Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score	Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score, range 10 to 60	Baseline (T0)
Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score	Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score, range 10 to 60	After 14 days of supplementation (T14)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant Crying Frequency	The Frequency of Infant Crying Daily	baseline day, to day 14
Number of Hours of Infants Sleeping	Number of Hours of Infants Sleeping Daily	baseline day, to day 14

Collaborators and Investigators

• Sponsor: a2 Milk Company Ltd.
• Investigators: Principal Investigator: Zhixu Wang, MD, School of Public Health, Nanjing Medical University; Principal Investigator: Fan Yang, PhD, West China Second Hospital, Sichuan University; Principal Investigator: Yi Sun, MD, Shanghai Tongren Hospital

Publications and helpful links

General Publications

• Ul Haq MR, Kapila R, Sharma R, Saliganti V, Kapila S. Comparative evaluation of cow beta-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut. Eur J Nutr. 2014 Jun;53(4):1039-49. doi: 10.1007/s00394-013-0606-7. Epub 2013 Oct 29.
• Iacono G, Merolla R, D'Amico D, Bonci E, Cavataio F, Di Prima L, Scalici C, Indinnimeo L, Averna MR, Carroccio A; Paediatric Study Group on Gastrointestinal Symptoms in Infancy. Gastrointestinal symptoms in infancy: a population-based prospective study. Dig Liver Dis. 2005 Jun;37(6):432-8. doi: 10.1016/j.dld.2005.01.009. Epub 2005 Mar 2.
• He M, Sun J, Jiang ZQ, Yang YX. Effects of cow's milk beta-casein variants on symptoms of milk intolerance in Chinese adults: a multicentre, randomised controlled study. Nutr J. 2017 Oct 25;16(1):72. doi: 10.1186/s12937-017-0275-0.
• Sheng X, Li Z, Ni J, Yelland G. Effects of Conventional Milk Versus Milk Containing Only A2 beta-Casein on Digestion in Chinese Children: A Randomized Study. J Pediatr Gastroenterol Nutr. 2019 Sep;69(3):375-382. doi: 10.1097/MPG.0000000000002437.
• Sheng XY, Buthmanaban V, van Lieshout GAA, Parikh P. Reduced Occurrence of Gastrointestinal Symptoms in Chinese Infants Fed Minimally Processed Commercially Available Formula: A Cross-Sectional Observational Study. J Nutr Metab. 2020 Mar 25;2020:1807397. doi: 10.1155/2020/1807397. eCollection 2020.
• van de Heijning BJ, Berton A, Bouritius H, Goulet O. GI symptoms in infants are a potential target for fermented infant milk formulae: a review. Nutrients. 2014 Sep 25;6(9):3942-67. doi: 10.3390/nu6093942.
• Ferreira-Maia AP, Matijasevich A, Wang YP. Epidemiology of functional gastrointestinal disorders in infants and toddlers: A systematic review. World J Gastroenterol. 2016 Jul 28;22(28):6547-58. doi: 10.3748/wjg.v22.i28.6547.
• Vandenplas Y, Abkari A, Bellaiche M, Benninga M, Chouraqui JP, Cokura F, Harb T, Hegar B, Lifschitz C, Ludwig T, Miqdady M, de Morais MB, Osatakul S, Salvatore S, Shamir R, Staiano A, Szajewska H, Thapar N. Prevalence and Health Outcomes of Functional Gastrointestinal Symptoms in Infants From Birth to 12 Months of Age. J Pediatr Gastroenterol Nutr. 2015 Nov;61(5):531-7. doi: 10.1097/MPG.0000000000000949. Erratum In: J Pediatr Gastroenterol Nutr. 2016 Mar;62(3):516.
• Shamir R, St James-Roberts I, Di Lorenzo C, Burns AJ, Thapar N, Indrio F, Riezzo G, Raimondi F, Di Mauro A, Francavilla R, Leuchter RH, Darque A, Huppi PS, Heine RG, Bellaiche M, Levy M, Jung C, Alvarez M, Hovish K. Infant crying, colic, and gastrointestinal discomfort in early childhood: a review of the evidence and most plausible mechanisms. J Pediatr Gastroenterol Nutr. 2013 Dec;57 Suppl 1:S1-45. doi: 10.1097/MPG.0b013e3182a154ff. No abstract available.
• Jianqin S, Leiming X, Lu X, Yelland GW, Ni J, Clarke AJ. Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk. Nutr J. 2016 Apr 2;15:35. doi: 10.1186/s12937-016-0147-z. Erratum In: Nutr J. 2016 Apr 29;15(1):45. doi: 10.1186/s12937-016-0164-y.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2023
• Primary Completion (Actual): August 17, 2023
• Study Completion (Actual): August 17, 2023

Study Registration Dates

• First Submitted: April 3, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 26, 2023

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Gut Health; A2 Full Cream Milk; Breastmilk Composition
• Additional Relevant MeSH Terms: Sleepiness; Gastrointestinal Diseases; Digestive System Diseases
• Other Study ID Numbers: 22-SM-12-A2-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No