NUPICO: Nutrigenomics, PUFA, Iron and Cognition Amongst Under-two-year-old Indonesian Children

Sponsor

Indonesia University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01504633

Collaborator

Wageningen University (Other)

240

Enrollment

Location

Arms

Duration (Months)

6.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Rationale: Review on the positive effect of long chain polyunsaturated fatty acids (LCPUFA), especially docosahexanoic acid (DHA), supplementation on cognitive function in human using randomized controlled trials (RCTs) showed that results in RCTs were mixed and inconsistent. It has been suggested that the effect may be subtle, which is currently difficult to detect, but could be significant, or there may be individual variation which mediate the effect.

Objectives: This study aims to assess gene-nutrient inter-relation in explaining the effect of LCPUFAs i.e. DHA and/or iron on cognitive functioning of children <24mo in Indonesia. Specifically the study's objectives are: (1) to assess effect of LCPUFA (as DHA oil) and iron (as iron supplement) in altering gene expressions, and (2) to assess the mediating effect of genes involved in fatty acid and iron metabolism in improving serum LCPUFA, alpha-linolenic acids (ALA), DHA and cognitive function.

Study design and study population: The study is a double-blind randomized controlled trial with children aged less than 24 months (window of opportunity). The study area is in East Lombok district, in West Nusa Tenggara province, Indonesia where nutrient intake including iron and presumably LCPUFA, is not optimal.

Intervention: The study is an intervention study, consisting of four groups: DHA, iron, DHA+iron, and placebo (60 subjects/group = 240 subjects in total). Capsule containing 100mg/d DHA or its placebo and syrup containing 16mg/d iron will be given daily for 24 weeks. Before and after the intervention child cognition (as Bayley Mental Developmental Index or MDI score), serum PUFA level, iron status (haemoglobin, transferrin receptor, ferritin), inflammation status (CRP, AGP), gene expression profiles, and potential confounders of child cognition such as lengt-for-age, weight-for-length, and weight-for-age Z-scores, stimulation/home environment, maternal characteristics will be collected.

Study outcome: The primary study outcomes will be cognitive score (as Bayley Mental Developmental Index or MDI score) and gene expression profiles. Secondary study outcomes will be serum PUFA level, iron status (haemoglobin, TfR, ferritin).

Nature and extent of the burden and risks benefit and group relatedness:

Subjects, who will be included into the study will invest 14 hours. The consumption of iron is not associated with any increased risk of iron overload both for infectious (including malaria) and chronic diseases nor consumption of n-3 fatty acids EPA and DHA exceed the US Food and Drug Administrator (FDA) Generally Recognized as Save (GRAS) limit. Venous blood of 5 mL will be drawn at baseline and endline. During screening, children with severe anaemia (Hb<70g/L) will be excluded from the study and referred to the local public health center for further treatment.

Condition or Disease	Intervention/Treatment	Phase
Cognitive Ability, General	Dietary Supplement: DHA/EPA and iron supplementation	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Official Title:

Can NUtrigenomics / Nutrigenetics Help Explain the Mixed Results on Effect of LCPUFA (DHA) and Iron on Child COgnition?

Study Start Date :

Dec 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2014

Anticipated Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DHA+EPA Group DHA/EPA capsule (100mg DHA + 20mg) and placebo syrup per day	Dietary Supplement: DHA/EPA and iron supplementation 24-week supplementation consisting of daily dosage of DHA/EPA or placebo capsule and iron/placebo syrup Capsule: DHA/EPA (100mg DHA + 20mg per day) or placebo Syrup: Fe syrup (16mg elemental iron per day) or placebo
Experimental: Fe Group Placebo capsule and Fe syrup (16mg elemental iron) per day	Dietary Supplement: DHA/EPA and iron supplementation 24-week supplementation consisting of daily dosage of DHA/EPA or placebo capsule and iron/placebo syrup Capsule: DHA/EPA (100mg DHA + 20mg per day) or placebo Syrup: Fe syrup (16mg elemental iron per day) or placebo
Experimental: DHA/EPA+Fe Group DHA/EPA capsule (100mg DHA + 20mg) and Fe syrup (16mg elemental iron) per day	Dietary Supplement: DHA/EPA and iron supplementation 24-week supplementation consisting of daily dosage of DHA/EPA or placebo capsule and iron/placebo syrup Capsule: DHA/EPA (100mg DHA + 20mg per day) or placebo Syrup: Fe syrup (16mg elemental iron per day) or placebo
Experimental: Placebo Group Placebo capsule and placebo syrup	Dietary Supplement: DHA/EPA and iron supplementation 24-week supplementation consisting of daily dosage of DHA/EPA or placebo capsule and iron/placebo syrup Capsule: DHA/EPA (100mg DHA + 20mg per day) or placebo Syrup: Fe syrup (16mg elemental iron per day) or placebo

Outcome Measures

Primary Outcome Measures

change in cognitive function (MDI score) [within 24 weeks after start of intervention]
Mental Developmental Index (MDI) score of Bayley Scale of Infant Development (BSID)

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months to 16 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Child aged 12 to 17months old
Both father and mother of Sasak ethnicity
Currently breastfed

Exclusion Criteria:

Birth weight <2500 grams (LBW)
Congenital malformation and/or disorder that interfered with adequate functioning in daily life
Hemoglobin value below 70 g/L
Malaria
Maternal depression