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

Tracking Information
First Submitted Date ICMJE	December 31, 2011
First Posted Date ICMJE	January 5, 2012
Last Update Posted Date	February 26, 2014
Study Start Date ICMJE	December 2011
Estimated Primary Completion Date	December 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 3, 2012)	change in cognitive function (MDI score) [ Time Frame: within 24 weeks after start of intervention ]; Mental Developmental Index (MDI) score of Bayley Scale of Infant Development (BSID)
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01504633 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Nutrigenomics, PUFA, Iron and Cognition Amongst Under-two-year-old Indonesian Children
Official Title ICMJE	Can NUtrigenomics / Nutrigenetics Help Explain the Mixed Results on Effect of LCPUFA (DHA) and Iron on Child COgnition?
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Condition ICMJE	Cognitive Ability, General
Intervention ICMJE	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
Study Arms	Experimental: DHA+EPA Group DHA/EPA capsule (100mg DHA + 20mg) and placebo syrup per day Intervention: Dietary Supplement: DHA/EPA and iron supplementation; Experimental: Fe Group Placebo capsule and Fe syrup (16mg elemental iron) per day Intervention: Dietary Supplement: DHA/EPA and iron supplementation; Experimental: DHA/EPA+Fe Group DHA/EPA capsule (100mg DHA + 20mg) and Fe syrup (16mg elemental iron) per day Intervention: Dietary Supplement: DHA/EPA and iron supplementation; Experimental: Placebo Group Placebo capsule and placebo syrup Intervention: Dietary Supplement: DHA/EPA and iron supplementation
Publications *	Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1467S-1476S. Review.; Bouwens M, van de Rest O, Dellschaft N, Bromhaar MG, de Groot LC, Geleijnse JM, Müller M, Afman LA. Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Am J Clin Nutr. 2009 Aug;90(2):415-24. doi: 10.3945/ajcn.2009.27680. Epub 2009 Jun 10.; Bouwens M, Grootte Bromhaar M, Jansen J, Müller M, Afman LA. Postprandial dietary lipid-specific effects on human peripheral blood mononuclear cell gene expression profiles. Am J Clin Nutr. 2010 Jan;91(1):208-17. doi: 10.3945/ajcn.2009.28586. Epub 2009 Nov 18.; Cunnane SC, McAdoo KR. Iron intake influences essential fatty acid and lipid composition of rat plasma and erythrocytes. J Nutr. 1987 Sep;117(9):1514-9.; El-khayat H, Shaaban S, Emam EK, Elwakkad A. Cognitive functions in protein-energy malnutrition: in relation to long chain-polyunsaturated fatty acids. Pak J Biol Sci. 2007 Jun 1;10(11):1773-81.; Idjradinata P, Pollitt E. Reversal of developmental delays in iron-deficient anaemic infants treated with iron. Lancet. 1993 Jan 2;341(8836):1-4.; Koletzko B, Demmelmair H, Schaeffer L, Illig T, Heinrich J. Genetically determined variation in polyunsaturated fatty acid metabolism may result in different dietary requirements. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:35-44; discussion 44-9. doi: 10.1159/000146246. Review.; Kwik-Uribe CL, Gietzen D, German JB, Golub MS, Keen CL. Chronic marginal iron intakes during early development in mice result in persistent changes in dopamine metabolism and myelin composition. J Nutr. 2000 Nov;130(11):2821-30.; McCann JC, Ames BN. Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. Am J Clin Nutr. 2005 Aug;82(2):281-95. Review.; McCann JC, Ames BN. An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function. Am J Clin Nutr. 2007 Apr;85(4):931-45. Review.; Murray-Kolb LE, Beard JL. Iron deficiency and child and maternal health. Am J Clin Nutr. 2009 Mar;89(3):946S-950S. doi: 10.3945/ajcn.2008.26692D. Epub 2009 Jan 21.; Oloyede OB, Folayan AT, Odutuga AA. Effects of low-iron status and deficiency of essential fatty acids on some biochemical constituents of rat brain. Biochem Int. 1992 Aug;27(5):913-22.; Smuts CM, Tichelaar HY, van Jaarsveld PJ, Badenhorst CJ, Kruger M, Laubscher R, Mansvelt EP, Benadé AJ. The effect of iron fortification on the fatty acid composition of plasma and erythrocyte membranes in primary school children with and without iron deficiency. Prostaglandins Leukot Essent Fatty Acids. 1995 Jan;52(1):59-67.; Stangl GI, Kirchgessner M. Different degrees of moderate iron deficiency modulate lipid metabolism of rats. Lipids. 1998 Sep;33(9):889-95.; Rajilić-Stojanović M, Heilig HG, Molenaar D, Kajander K, Surakka A, Smidt H, de Vos WM. Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults. Environ Microbiol. 2009 Jul;11(7):1736-51. doi: 10.1111/j.1462-2920.2009.01900.x. Epub 2009 Mar 11.; Fahmida U, Htet MK, Adhiyanto C, Kolopaking R, Yudisti MA, Maududi A, Suryandari DA, Dillon D, Afman L, Müller M. Genetic variants of FADS gene cluster, plasma LC-PUFA levels and the association with cognitive function of under-two-year-old Sasaknese Indonesian children. Asia Pac J Clin Nutr. 2015;24(2):323-8. doi: 10.6133/apjcn.2015.24.2.17.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Estimated Enrollment ICMJE; (submitted: January 3, 2012)	240
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	December 2014
Estimated Primary Completion Date	December 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	12 Months to 16 Months (Child)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Indonesia
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01504633
Other Study ID Numbers ICMJE	NUPICO-Indonesia
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Umi Fahmida, Indonesia University
Study Sponsor ICMJE	Indonesia University
Collaborators ICMJE	Wageningen University
Investigators ICMJE	Principal Investigator: Umi Fahmida, PhD SEAMEO Regional Center for Food and Nutrition (RECFON) University of Indonesia
PRS Account	Indonesia University
Verification Date	February 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP