A First-ever Research Collaboration to Characterize MRI Measured Neural Flexibility Development in Chinese Toddlers

Recruiting

• Conditions: Growth & Development; Brain
• Interventions: Radiation: MRI

• Registration Number: NCT04916652
• Lead Sponsor: Société des Produits Nestlé (SPN)

Brief Summary

The overall objective is to characterize the developmental characteristics of MRI measured neural flexibility, as an index of cognitive flexibility, in Chinese toddlers (32 to 42 months old).

Detailed Description

The primary objective of this clinical study is to characterize in Chinese toddlers ages 32 - 42 months old the developmental characteristics of MRI measured neural flexibility, as an index of cognitive flexibility, and to assess a range of executive functions (inhibit, shift, emotional control, working memory, plan/organize) using the Global Executive Composite summary score obtained from the BRIEF-P standardized rating scale.

Study Timeline

• Study First Submitted: 2020-10-29
• Study First Submitted QC: 2021-06-03
• Study First Posted: 2021-06-07
• Study Start: 2024-04-06
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-24
• Last Update Posted: 2025-06-25
• Primary Completion: 2025-08
• Study Completion: 2025-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Written informed consent has been obtained from the parent/legally acceptable representative.
2. Full-term birth (≥ 37 weeks and ≥ 2.5kg)
3. Typically developing Children aged between 32-34 months (2 years 8 months to 2 years10 month of age) at enrolment
4. Neurotypical development as assessed by interview
5. No major risk factors for learning, neurologic, or psychiatric disorder as assessed by interview [defined as a diagnosed learning neurologic or psychiatric disorder in a first degree relative (e.g. parents, siblings)].
6. Dietary requirement detailed below:

S-26 GOLD or ULTIMA GUM--fed group:

I. Daily consumption of S-26 GOLD or ULTIMA GUM for the last 60 days (2 months) II. Desire of the parent to continue feeding GUM during the course of the study

Cow's milk-fed group:

I. Daily consumption of cow's milk or for the last 60 days (2 months) II. Desire of the parent to continue feeding cow's milk during the course of the study

Exclusion Criteria

1. Delayed birth ( > 41 weeks gestation) as reported in medical record
2. Birth Weight < 2500 g or small for gestational age (birth weight below the 10th percentile) or large for gestational age (birth weight above the 90th percentile) as reported in medical record
3. History of neurological (e.g., head injury, epilepsy), psychiatric or developmental disorder in the toddler as assessed by interview
4. History of diagnosed neurological (e.g., head injury, epilepsy), psychiatric or developmental disorder in parents or siblings, as assessed by interview
5. In utero exposure to alcohol abuse or illicit substances as defined as diagnosis of current substance use disorder in the biological mother and guidelines set by the American College of Obstetricians and Gynecologists and the Royal College of Physicians
6. Multiple birth as reported in medical record
7. Complicated pregnancy (e.g., preeclampsia, gestational diabetes) as assessed by medical interview/ medical record
8. Abnormal screening laboratory values and studies considered to be clinically significant in the opinion of the Investigator (e.g., metabolic disease screening, neonatal bilirubin)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cow's milk-fed group:	MRI	Parent(s) to continue feeding their child cow's milk during the course of the study. We will collect information from parents on the cow's milk consumed for a maximum of 2 months prior to the study start and during the course of the study.
S-26 GOLD/ULTIMA GUM-fed group:	MRI	Parent(s) to continue feeding their child S-26 GOLD or ULTIMA GUM during the course of the study. We will collect information from parents on the S-26 GOLD/ ULTIMA GUM for a maximum of 2 months prior to the study start and during the course of the study.

Primary Outcome Measures

Name	Time	Method
Neural flexibility	at baseline and 42 months after baseline	MRI-derived neural flexibility associated with cognitive flexibility (including anterior cingulate cortex, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, anterior insula, interior frontal junction, superior parietal lobule, precuneus, intraparietal sulcus, and temporoparietal junction)
Global Executive Composite (GEC) score	at baseline and 42 months of age	executive functions (inhibit, shift, emotional control, working memory, plan/organize) using the Global Executive Composite summary score obtained from the BRIEF-P standardized rating scale

Secondary Outcome Measures

Name	Time	Method
Brain structure (brain regions volume)	at baseline and 42 months of age	Brain structure (brain regions volume) measured using MRI, including the hippocampal
Brain structure (cortical surface area)	at baseline and 42 months of age	Brain structure (cortical surface area) measured using MRI
Brain structure (cortical thickness)	at baseline and 42 months of age	Brain structure (cortical thickness) measured using MRI
Brain structure (myelination)	at baseline and 42 months of age	Brain structure (myelination) measured using MRI
Brain function (network topologies)	at baseline and 42 months of age	Brain functional network topologies of the nine commonly assessed brain functional networks, including the primary visual, secondary visual, visual association, motosensory, default mode, frontoparietal, medial frontal, subcortical and cerebellum networks using MRI
Brain function (connection strengths)	at baseline and 42 months of age	Brain functional connection strengths of the nine commonly assessed brain functional networks, including the primary visual, secondary visual, visual association, motosensory, default mode, frontoparietal, medial frontal, subcortical and cerebellum networks using MRI
Cognitive flexibility	at baseline and 42 months of age	Using the Dimensional Change Card Sort (DCCS) task
Children development	at baseline and 42 months of age	Verbal Comprehension, Visual Spatial, Working Memory, and IQ using Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV)
School readiness	at 42 months of age	Using Early Human Capability Index (eHCI)
Children behavior (for toddlers)	at baseline and 42 months of age	Using the Early Childhood Behavioral Questionnaire (ECBQ)
Curiosity	at baseline and 42 months of age	Using the Curiosity Questionnaire
Sleep quality	at baseline and 42 months of age	Sleep quality, duration and efficiency (total sleep time / duration of sleep episode \*100) computed using the Brief Infant Sleep Questionnaire (BISQ). In addition, an actigraphy in combination with a sleep diary will be used during home period and their relationship will indicate the sleep quality
Home environment	at baseline and 8 months after baseline	Using validated Child Feeding Practice Questionnaire. In addition, to complete the feeding and adverse events calendar monthly during home period
Feeding practice	at baseline and 42 months of age	Using the Early Feeding Practice Questionnaire. In addition, the feeding and adverse events calendar monthly during home period
Fecal microbiota composition	at baseline and 42 months of age	Measured via the shotgun metagenomics sequencing for species composition and functional pathways through stool samples collected

Trial Locations

Locations (1)

Shanghai Children's Medical Center; 🇨🇳 Shanghai, Shanghai, China