Toddler Milk Intervention Trial (TOMI)

Effects of Milk Protein Intake in Young Children on Early Growth and Later Obesity Risk: a Multicentre Randomized Clinical Trial

To assess growth of children (enrolled between 11.5 and 13.5 months) fed with two iso-energetic, young-child formulas with different protein content during the second year of life

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Young-child formula with low protein content; Dietary supplement: Young-child formula with protein content similar to that of cow's milk

Detailed Description

This study is designed to investigate in a randomized double-blind parallel-group trial the growth and metabolic effects of different contributions of protein to total energy intakes in healthy children during the second year of life

• Study Type: Interventional
• Enrollment (Actual): 1618
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 80337
    • Dr Von Hauner Children's hospital
• Spain
  • Tarragona, Spain
    • Hospital Universitari Joan 23 de Tarragona. Universitat Rovira i Virgili.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 months to 1 year (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Having obtained his/her parents' (or his/her legally accepted representative [LAR's] written informed consent and having evidence of personally signed and dated informed consent document indicating that the child's parents/LAR have been informed of all pertinent aspects of the study
• Child was born full term (≥ 37 weeks of gestation)
• Age at enrollment: between 11.5 months and 13.5 months of age
• 2.5 kg ≤ birth weight ≤ 4.5 kg
• Born from a singleton pregnancy
• Child's parent(s)/LAR is of legal age of consent, has sufficient local language skills to complete the informed consent and other study documents, is able to be contacted directly by telephone throughout the study, and is willing and able to fulfill the requirements of the study protocol.

Exclusion Criteria:

• Diagnosed disorder considered to interfere with nutrition or growth (e.g. malabsorptive disorders as short bowel syndrome, inflammatory bowel disease; neurological and congenital disorders that may delay growth as cerebral palsy, agenesis of the corpus callosum, spina bifida, Down Syndrome, Cri Du Chat; disorders that may lead to obesity: Prader willi syndrome, Angelman syndrome, etc.)
• Cows' milk allergy
• Lactose intolerance
• Participation in any other interventional clinical trial during the 4 weeks prior to enrollment
• Infant who is being breastfed at the time of enrollment
• Infant who does not usually drink 300ml of cow's and/or formula milk per day
• Institutionalized children
• Child or child's family who in the Investigator's judgment cannot be expected to comply with the protocol or study procedures

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental formula; Young-child formula with low protein content	Dietary supplement: Young-child formula with low protein content; Young-child formula with low protein content
Active Comparator: Control formula; Young-child formula with protein content similar to that of cow's milk	Dietary supplement: Young-child formula with protein content similar to that of cow's milk; Young-child formula with protein content similar to that of cow's milk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMI-for-age z-score	WHO-growth standard	Age 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMI-for-age z-score		Age 72 months
The percentage of overweight and obese children	CDC definition: Overweight above 85th to less than the 95th percentile and obese 95th percentile or greater and analyzed by the method of Peacock (Dichotomising continuous data while retaining statistical power using a distributional approach, Statistics in medicine, 2012).	Age 24 months
The percentage of overweight and obese children		Age 72 months
Growth parameters: Anthropometry: Weight, Length, Heel knee length, Mid-arm circumference, Waist circumference, Hip circumference (only 48 months and 72 months), Head circumference, Triceps skinfold, Subscapular skinfold		Age 12, 18, 24, 48 and 72 months
Child's development: Parental rating of child development with Ages & Stages Questionnaires®		Age 24 and 48 months
Body composition: air displacement plethysmography		at 24, 48 and 72 months of age
Metabolomic profile: Plasma and urine metabolic indicators of energy and protein metabolism (metabolomics with a focus on carnitines, amino acid catabolism, ketone bodies, Krebs cycle, and bacterial utilization of protein and carbohydrates)		Age 12, 18, 24, 48 and 72 months
DNA methylation pattern: Methylation status of specific DNA regions (e.g. CpG sites)		Age 12, 24 and 72 months
Blood pressure		Age 48 and 72 months
Dietary intake: 24-hour recall		Age 12, 18, 24, 48 and 72 months
Metabolic and endocrine markers: Blood and Urine markers	Blood: Complete blood count, Glucose, Creatinine, Ferritin (measured only at 24 months), 25-OH vitamin D (measured only at 24 months), Triglycerides, Total cholesterol, HDL- and LDL-cholesterol, Insulin, FGF-21, IGF-1, IGF-BP2, IGF-BP3, Leptin, Adiponectin, Ghrelin, Amino Acids, Serum albumin, Urea, C-reactive protein, Osteocalcin / Urine: Calcium, C-peptide, Creatinine, Urea nitrogen	Age 12, 24 and 72 months

Collaborators and Investigators

• Sponsor: Société des Produits Nestlé (SPN)

Publications and helpful links

General Publications

• Grote V, Jaeger V, Escribano J, Zaragoza M, Gispert M, Grathwohl D, Koletzko B. Effect of milk protein content in Toddler formula on later BMI and obesity risk: protocol of the multicentre randomised controlled Toddler Milk Intervention (ToMI) trial. BMJ Open. 2021 Dec 7;11(12):e048290. doi: 10.1136/bmjopen-2020-048290.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): October 1, 2024

Study Registration Dates

• First Submitted: August 31, 2016
• First Submitted That Met QC Criteria: September 14, 2016
• First Posted (Estimated): September 20, 2016

Study Record Updates

• Last Update Posted (Actual): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 13.29.INF

Plan for Individual participant data (IPD)

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