Efficacy of Two HMOs in Chinese Infants

Efficacy of a Ready to Feed (RTF) Starter Liquid Infant Formula Containing 2'FL and LNnT in Chinese Infants: A Double-blind, Randomized Controlled Trial Including a Breastfed Reference Group

This is a randomized, controlled, double-blind, intervention trial of healthy male and female term infants to evaluate the efficacy of the 2 HMOs on beneficially modulating the gut microbiota, gut maturation, gut barrier integrity, immune response, and other developmental outcomes in healthy Chinese infants. The trial consists of 2 randomized formula-fed groups, and a non-randomized breastfed reference group.

Study Overview

• Status: Recruiting
• Conditions: Healthy Infants
• Intervention / Treatment: Other: Experimental Group (EG); Other: Control Group (CG)

• Study Type: Interventional
• Enrollment (Estimated): 262
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qiaoji Li; Phone Number: 008613910051543; Email: qiaoji.li@rd.nestle.com
• Study Contact Backup: Name: Joyce Li; Phone Number: 008615810125435; Email: Joyce.Li@rd.nestle.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • The International Peace Maternity & Child Health Hospital of China Welfare Institute
    • Contact: Zhiwei Liu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy male and female infants of post-natal age of 3-14 days (date of birth = day 0), inclusive, at enrolment
• Evidence of personally signed and dated informed consent document indicating that the infant's parent(s)/ legally accepted representatives LAR have been informed of all pertinent aspects of the trial.
• Infants whose parent(s) have reached the legal age of majority in China.
• Infants whose parent(s)/LAR are willing and able to comply with scheduled visits, and the requirements of the trial protocol.
• Infants whose parent(s)/LAR can be contacted directly by telephone throughout the trial.
• Infants whose parent(s)/LAR have a working freezer.
• Singleton, healthy, full-term gestational birth (≥ 37 completed weeks of gestation), with a birth weight of ≥ 2.5 kg and ≤ 4.5 kg.
• For the formula-fed groups: infant is exclusively consuming and tolerating a cow' s milk infant formula for at least 3 days prior to enrolment. The infant's mother has independently elected not to breastfeed.
• For the breastfed reference group: infant has been exclusively consuming breastmilk since birth (small amounts of other feedings allowed during the first three days of life before breastfeeding is well-established) and the infant's mother has made the decision to continue exclusively breastfeeding until at least 3 months of age.

Exclusion Criteria:

• Infants with conditions requiring infant feedings other than those specified in the protocol.
• Infants receiving complementary foods or liquids defined as 4 or more teaspoons per day or approximately 20 g per day of complementary foods or liquids at or prior to enrolment.
• Infants who have a medical condition or history that could increase the risk associated with trial participation or interfere with the interpretation of trial results, including: Evidence of major congenital malformations (e.g., cleft palate, extremity malformation). Documented or suspected systemic or congenital infections (e.g., human immunodeficiency virus, cytomegalovirus, syphilis). Previous or ongoing severe medical or laboratory abnormality (acute or chronic) which, in the judgment of the investigator, would make the infant inappropriate for entry into the trial.
• Infants who are presently receiving or have received prior to enrolment probiotic supplements or any of the following: medication(s) or supplement(s) which are known or suspected to affect the following: fat digestion, absorption, and/or metabolism (e.g., pancreatic enzymes); stool characteristics and microbiota (e.g., oral and systemic antibiotics, glycerine suppositories, bismuth-containing medications, docusate, Maltsupex, or lactulose); growth (e.g. insulin or growth hormone); gastric acid secretion.
• Currently participating or having participated in another clinical trial since birth.
• Infant who has known or suspected cows' milk protein intolerance / allergy, lactose intolerance, soy intolerance / allergy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group (EG); Starter infant formula supplemented with two HMOs. Following the intervention period, the infants will consume a standard infant follow-up formula (non-trial formula).	Other: Experimental Group (EG); Starter infant formula will be administered to the participants orally, ad libtium to 6 months, after which they will transfer to a classical follow-up formula (non-trial formula) until the end of the trial (12 months of age).
Active Comparator: Control Group (CG); Starter infant formula not supplemented with two HMOs. Following the intervention period, the infants will consume a standard infant follow-up formula (non-trial formula).	Other: Control Group (CG); Starter infant formula will be administered to the participants orally, ad libtium to 6 months, after which they will transfer to a classical follow-up formula (non-trial formula) until the end of the trial (12 months of age).
No Intervention: Breastfed Group (BG); Breast Milk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bifidobacteria abundance in fecal samples	Bifidobacteria abundance using qPCR technology	just prior to 3 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiota composition	Relative abundance of beneficial and potentially pathogenic species using next generation sequencing (NGS) technology	From enrollment until 12 months of age
Fecal metabolism	Fecal pH analyzed using HPLC as well as targeted or untargeted metabolomics profiling	From enrollment until 12 months of age
Fecal metabolism	Short chain fatty acids analyzed using HPLC as well as targeted or untargeted metabolomics profiling	From enrollment until 12 months of age
Fecal markers of intestinal immune health	Fecal secretory IgA measured by ELISA	From enrollment until 6 months of age
Fecal markers of gut barrier function	Calprotectin measured by ELISA	From enrollment until 6 months of age
Fecal markers of gut barrier function	α-1-antitrypsin measured by ELISA	From enrollment until 6 months of age
Fecal markers of gut barrier function	Lipocalin-2 measured by ELISA	From enrollment until 6 months of age
Fecal markers of inflammation	Levels of cytokines such as IL-1β measured by ELISA	From enrollment until 6 months of age
Fecal markers of inflammation	Levels of cytokines such as IFN-γ measured by ELISA	From enrollment until 6 months of age
Fecal markers of inflammation	Levels of cytokines such as TNF-α measured by ELISA	From enrollment until 6 months of age
Stool patterns	Stool frequency, consistency, and difficulty in passing stools assessed using a 1-day retrospective stool consistency diary (24-hr recall)	From enrollment until 14 days
Stool patterns	Stool frequency, consistency, and difficulty in passing stools assessed using a 3-day prospective collection recorded in the stool consistency diary.	From enrollment until 12 months of age
GI symptoms and behaviors	IGSQ-13 Questionnaire	From enrollment until 6 months of age
Immune competence	Pediatric Immune System Index score	From enrollment until 12 months of age
Infant sleep duration and night-time wakings per 24 hours	Brief infant sleep questionnaire (BISQ)	From enrollment until 6 months of age
Infant Health Related Quality of Life	Infant Toddler Quality of Life Questionnaire (ITQoL -SF47)	From enrollment until 6 months of age
Growth	Weight (g) and corresponding Z-scores	From enrollment until 12 months of age
Growth	Length (cm) and corresponding Z-scores	From enrollment until 12 months of age
Growth	Head circumference (cm) and corresponding Z-scores	From enrollment until 12 months of age
Growth	Weight gain and corresponding Z-scores	From enrollment until 12 months of age
Growth	Length gain, corresponding Z-scores	From enrollment until 12 months of age
Physical Examination		At enrollment and at 12 months of age
Infant Illness	Infant Illness Diary	From enrollment until 12 months of age
Infant illness, infections and medication usage	AEs and Serious Adverse Events (SAEs)	From the time the informed consent form has been signed at enrollment infant age less than 3 days until 12 months of age
Medication use (type and duration)	Concomitant medication form and Infant Illness Diary	From enrollment until 12 months of age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Formula feeding	Total quantity of milk consumed for formula-feeding	From enrollment until 12 months of age
Breastfeeding	The frequency of breastfeeding, duration and type of breastfeeding (exclusive, predominant, partial)	From enrollment until 12 months of age
Infant dietary pattern	3-day food diary	From 6 months of age until 12 months of age

Collaborators and Investigators

• Sponsor: Société des Produits Nestlé (SPN)
• Investigators: Principal Investigator: Wei Cai, MD, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Publications and helpful links

General Publications

• Wang Y, Le Roy CI, Li J, Han S, Liu Z, Lahiry A, Sahu H, Li Q, Dong J, Mondragon A, Samuel TM, Cai W. Efficacy of a Ready-to-Feed Starter Liquid Infant Formula Containing 2-Fucosyllactose and Lacto-N-Neotetraose in Chinese Infants: Protocol for a Double Blind, Randomized Controlled Trial. JMIR Res Protoc. 2025 Oct 31;14:e66489. doi: 10.2196/66489.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Growth; Tolerance; Immune response; Human Milk Oligosaccharides; Infant gut microbiota; Infant gut health
• Additional Relevant MeSH Terms: Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Control Groups
• Other Study ID Numbers: 2312INF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No