Clinical trial NCT02437721: Suitability of an Infant Formula With L-5-Methyltetrahydrofolate for the Particular Nutritional Use in Infants
Official title: Suitability of an Infant Formula With L-5-Methyltetrahydrofolate for the Particular Nutritional Use in Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Growth and Development
Lead sponsor: DSM Nutritional Products, Inc.
Sponsor class: INDUSTRY
Collaborators: name: University Clinic Dr Dragisa Misovic-Dedinje
name: HiPP GmbH & Co. Vertrieb KG
name: Institute for Laboratory Diagnostics Konzilijum
name: Bevital AS
name: Charite University, Berlin, Germany
name: Sermon CRO
name: Ludwig-Maximilians - University of Munich
First posted: 2015-05-08
Enrollment: 360
Sex: ALL
Minimum age (years): 1
Maximum age (years): 27
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The study is designed to show equivalence of an infant formula containing L-5- Methyltetrahydrofolate (MTHF) compared to a standard infant formula containing folic acid in respect to weight gain of healthy term infants receiving these infant formulae exclusively during the first 4 months of life. Healthy non breast fed infants will be randomized to receive either a standard infant formula with folic acid or a corresponding formula with MTHF instead of folic acid. Besides weight and length further anthropometric measures will be taken monthly from the age of 4 weeks to the age of 16 weeks and at the age 4 and 16 weeks blood samples will be taken for the determination of folate status and genotyping. As a reference the same measures will be taken in a group of breast fed infants, whose mothers' folate status will be determined as well.


Eligibility criteria: Inclusion Criteria:

* Written informed consent (by parents, caregiver)
* Healthy male or female infants \<28 days of life
* Gestational age at delivery ≥37 and ≤42 weeks
* Birth weight between 2500 - 4500g
* Parents / Caregivers are able to speak Serbian language

Exclusion Criteria:

* Serious acquired or congenital diseases that is expected to interfere with normal feeding or growth
* Feeding of more than 10% of energy (1 bottle/day) from sources other than the formula (or breast milk in the reference group) at inclusion
* Participation in another clinical study
* Mothers with diabetes mellitus (including gestational diabetes)
* Reason to presume that the parents are unable to meet the study plan requirements
* Diseases of the mother which have an effect on the child's gastro-intestinal tract/ability to be fed
* Major abnormalities in hematological parameters
* Major abnormalities in hepatic, renal or metabolic functions
* Use of medication and vitamin supplements except vitamin K or D supplementation or vaccination
* Mother follows a vegan diet

Primary outcomes:
measure: weight gain (gram/day)
timeFrame: age of 4 weeks until age of 16 weeks
Secondary outcomes:
measure: body length gain (cm/day)
timeFrame: age of 4 weeks until age of 16 weeks
measure: fronto-occipital head circumference gain (in cm/day)
timeFrame: at age of 4 weeks and at the age of 16 weeks
measure: dietary intake of study formula, non-study formula, additional liquids and solids
timeFrame: during the period age 4 weeks to age 16 weeks
measure: feeding related behavior questionnaire
timeFrame: during the period age 4 weeks to age 16 weeks
measure: stool characteristics (color and consistency)
timeFrame: during the period age 4 weeks to age 16 weeks
Other outcomes:
measure: plasma levels of 5-MTHF in infants
timeFrame: at age of 4 weeks and at the age of 16 weeks
measure: plasma levels of folic acid in infants
timeFrame: at age of 4 weeks and at the age of 16 weeks
measure: plasma levels of 5-Formyl-tetrahydrofolate (fTHF) in infants
timeFrame: at age of 4 weeks and at the age of 16 weeks
measure: plasma levels of 4-Alfa-hydroxy-5-methyl-THF (hmTHF) in infants
timeFrame: at age of 4 weeks and at the age of 16 weeks
measure: plasma levels of Para-aminobenzoylglutamate (pABG) in infants
timeFrame: at age of 4 weeks and at the age of 16 weeks
measure: plasma levels of Acetamidobenzoylglutamate (apABG) in infants
timeFrame: at age of 4 weeks and at the age of 16 weeks
measure: red cell total folate in infants
timeFrame: at age of 4 weeks and at the age of 16 weeks
measure: plasma levels of 5-MTHF in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: breast milk levels of 5-MTHF in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: plasma levels of folic acid in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: breast milk levels of folic acid in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: plasma levels of fTHF in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: breast milk levels of fTHF in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: plasma levels of hmTHF in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: breast milk levels of hmTHF in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: plasma levels of pABG in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: breast milk levels of pABG in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: plasma levels of apABG in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: breast milk levels of apABG in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: hemoglobin value of the breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: hematocrit value of the breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: mean corpuscular volume (MCV) of the breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: weight of infants
timeFrame: at infantile age 1 year
measure: length of infants
timeFrame: at infantile age 1 year
measure: head circumference of infants
timeFrame: at infantile age 1 year
measure: hemoglobin value of infants
timeFrame: between Day 1 and Day 27 of life, at infantile age of 16 weeks and of 12 months
measure: hematocrit value of infants
timeFrame: between Day 1 and Day 27 of life, at infantile age of 16 weeks and of 12 months
measure: mean corpuscular volume (MCV) of infants
timeFrame: between Day 1 and Day 27 of life, at infantile age of 16 weeks and of 12 months
measure: infantile genotype of methylenetetrahydrofolate-reductase
timeFrame: at infantile age 4 weeks
measure: intake of folic acid in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
measure: intake of MTHF in breast feeding mothers
timeFrame: at the infantile age of 8 weeks
Locations:
city: Belgrade
country: Serbia
facility: KBC Dr Dragiša Mišović-Dedinje
city: Belgrade
country: Serbia
facility: HiPP Clinical Study Center
Study officials:
affiliation: Ludwig-Maximilians - University of Munich
name: Berthold Koletzko, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Troesch B, Demmelmair J, Gimpfl M, Hecht C, Lakovic G, Roehle R, Sipka L, Trisic B, Vusurovic M, Schoop R, Zdjelar S, Koletzko B; MEFOLIN Study Group. Suitability and safety of L-5-methyltetrahydrofolate as a folate source in infant formula: A randomized-controlled trial. PLoS One. 2019 Aug 19;14(8):e0216790. doi: 10.1371/journal.pone.0216790. eCollection 2019.