Clinical trial NCT05670678: Improved Respiratory Infection by Consuming Lactoferrin Fortified a2 Growing up Formula in Children of 2 to 3 Year Old
Official title: Improved Respiratory Infection Outcomes Associated With Lactoferrin Fortified a2 Growing up Formula Consumption in Children of 2 to 3 Year Old: a Randomized, Open Label Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Respiratory Infection
Diarrheal Disease
Keywords: growing up stage 3 formula
lactoferrin
acute respiratory infection
diarrheal disease
Lead sponsor: a2 Milk Company Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
First posted: 2023-01-04
Enrollment: 200
Sex: ALL
Minimum age (years): 2
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Full term born children who are 2-3 years old and consume Milk or milk-based beverage regularly

Brief summary: The goal of this observational study is to compare the incidence of ARI and/or diarrheal disease associated with feeding different formulas with and without lactoferrin supplement in children of 2-3 years old. 200 children eligible for the study will be enrolled from two study sites and randomly assigned to two groups (a2 growing up stage 3 formula puls lactoferrin supplement, and Enfinitas growing up stage 3 formula) to feed for 90 days. About 160 children (80 for each group) are expected to finish the study, and data will be collected during the four visits across the study.

Researchers will compare the two groups to see if there is significant decrease of the occurrence of diarrheal disease and/or acute respiratory infection for children fed with a2 growing up stage 3 formula puls lactoferrin supplement

Detailed description: This study is two arms, opening parallel-designed, observational study. Diarrheal and infectious episodes, including acute upper and lower respiratory infections (ARI), changes in stool patterns, use of systemic antibiotics, adverse events and study formula consumption will be compared in children 2 - 3 years of age who are assigned to receive one of the two following study formulas for a 3-month feeding period: a2 growing up stage 3 formula puls lactoferrin supplement and Enfinitas growingup stage 3 formula.

200 children eligible for the study will be enrolled from two study sites and randomly assigned to two groups to feed for 90 days. About 160 children (80 for each group) are expected to finish the study, and data of primary and secondary outcomes will be collected during the four visits across the study. A sample size of 80 completed per group is needed to achieve a 80% power.

The Andersen-Gill model will be used to model the primary outcome (recurrent event of either diarrheal disease or an acute respiratory infection) under the framework of the proportional hazard assumption. For other secondary outcomes such as duration of acute respiratory infections(ARI) and/or diarrheal disease, episodes of systemic antibiotic use,amount of study formula consumed,changes in stool pattern and cost of treatment will also be analyzed.

Eligibility criteria: Inclusion Criteria:

* Full term born children current aged 2-3 years old
* Birth weight not less than 2500g (5lb 8oz)
* Consumes Milk or milk-based beverage regularly before recruitment
* Informed consent signed
* Parents or guardians of the infants committ not to participate in interventional clinical research during the intervention

Exclusion Criteria:

* Has a potential risk of metabolic or chronic disease; Fetal malformation; Or present with condition(s) that the investigator believes may affect the infant's ability to be orally fed, the infant's normal growth/development, or the infant's health evaluation.
* In-take prebiotics or probiotic continuesly 15 days before the recruitment.
* Growth problems or other protencial risks.
* Larger-gestational age (LGA) babies born to mothers with gestational diabetes (defined as newborns whose birth weight is above the 90th percentile of average - Treated with antibiotics 7 days before study intervention.

Primary outcomes:
measure: Change of frequency of acute respiratory infection (ARI) and/or diarrheal disease
timeFrame: baseline day 0, day 90
Secondary outcomes:
measure: Duration of acute respiratory infections(ARI) and/or diarrheal disease
timeFrame: baseline day 0, visit 1 day 30, visit 2 day 60, visit 4 day 90
measure: Number of days of antibiotics treated
timeFrame: baseline day 0, visit 1 day 30, visit 2 day 60, visit 4 day 90
measure: Amount of study formula consumed
timeFrame: baseline day 0, visit 1 day 30, visit 2 day 60, visit 4 day 90
measure: Changes in stool pattern
timeFrame: baseline day 0, visit 1 day 30, visit 2 day 60, visit 4 day 90
measure: Cost of medical treatment
timeFrame: baseline day 0, visit 1 day 30, visit 2 day 60, visit 4 day 90
Other outcomes:
Locations:
city: Jinhua
country: China
facility: Nan Quan Community Hospital
state: Zhejiang
city: Jinhua
country: China
facility: Qiu Bin Community Hospital
state: Zhejiang
Study officials:
affiliation: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Xiaoyang Sheng, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li F, Jin X, Liu B, Zhuang W, Scalabrin D. Follow-up formula consumption in 3- to 4-year-olds and respiratory infections: an RCT. Pediatrics. 2014 Jun;133(6):e1533-40. doi: 10.1542/peds.2013-3598. Epub 2014 May 19.
citation: Leyer GJ, Li S, Mubasher ME, Reifer C, Ouwehand AC. Probiotic effects on cold and influenza-like symptom incidence and duration in children. Pediatrics. 2009 Aug;124(2):e172-9. doi: 10.1542/peds.2008-2666. Epub 2009 Jul 27.
citation: Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995 Jun;125(6):1401-12. doi: 10.1093/jn/125.6.1401.
citation: Boehm G, Lidestri M, Casetta P, Jelinek J, Negretti F, Stahl B, Marini A. Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2002 May;86(3):F178-81. doi: 10.1136/fn.86.3.f178.
citation: Cheng JB, Wang JQ, Bu DP, Liu GL, Zhang CG, Wei HY, Zhou LY, Wang JZ. Factors affecting the lactoferrin concentration in bovine milk. J Dairy Sci. 2008 Mar;91(3):970-6. doi: 10.3168/jds.2007-0689.