Effect of Double Fortification (Iron and Zinc) in Synbiotic Milk to Under 5 Years Stunted Children Growth

Effect of Double Fortification (Iron and Zinc) in Synbiotic Milk to Under 5 Years Stunted Children Growth : the Efforts to Achieve Target 2 SDGs Utilizing Local Natural Resources

The purpose of this study is to investigate the effects of double fortification (iron and zinc) in synbiotic milk (L.plantarum Dad13 and fructooligosaccharides) on under 5 years stunted children growth, gut microbiota composition, blood zinc and hemoglobin level, and cognitive level.

Study Overview

• Status: Unknown
• Conditions: Stunting
• Intervention / Treatment: Dietary supplement: fortified synbiotic milk; Dietary supplement: non-fortified synbiotic milk

Detailed Description

This is a parallel, quadruple-blind, randomized controlled trial to determine the effects of double fortification (iron and zinc) in synbiotic milk (containing 7 billion CFU L.plantarum Dad13 and 4 g fructooligosaccharides) on the gut microbiota composition, body height and weight, blood zinc and hemoglobin level, and cognitive level in under 5 years stunted children subjects. The duration of the study is 4 months, including a 2-week pre test and informed consent before randomization of subjects into treatment or control group, a 12-week intervention period, and a 2-week post test after the end of intervention. During the intervention period, subjects will be instructed to take 100 ml of fortified synbiotic milk or non-fortified synbiotic milk per day. They will also be asked to document consumed milk, any unusual symptoms or side effects of treatment. Diet will be monitored via 24-h dietary recalls and SQ-FFQ before and after treatment respectively. Changes in the gut microbiota composition will be determined by measuring bacterial population levels (Bifidobacteria, Lactobacillus, Enterobacteria, Prevotella, and Bacteroides) in stool sampled collected at baseline and 12 weeks by qPCR. Metabolic markers (calprotectin, hemoglobin, and zinc level) will be measured at baseline and 12-weeks in serum and plasma using biochemical and immuno-assay. Changes in the cognitive level, height for age Z-score collected at baseline and 12 weeks using Bayley Scales of Infant Development, 2nd Edition .

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • D.I.Yogyakarta
    • Sleman, D.I.Yogyakarta, Indonesia, 55281
      • Recruiting
      • Universitas Gadjah Mada
      • Contact: Siti Helmyati, DR.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age between 2 year to 5 years
• height per age z-score under -2 (stunting)
• parents sign inform consent form

Exclusion Criteria:

• have congenital abnormality
• lactose intolerant
• use antibiotic for more than 2 weeks
• consume micronutrient supplement (especially iron and zinc) in the last 3 months
• diagnose with chronic diseases and infection that interfere metabolism (i.e. tuberculosis, HIV, autoimmune disease, diabetes mellitus type 1)
• suffer marasmus and/or kwashiorkor
• not willing to continue the intervention

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fortified synbiotic milk; 100 ml fortified (7,47 mg ferrous sulphate and 4,33 mg zinc acetate) synbiotic milk containing 7 billion CFU Lactobacillus plantarum Dad13 in combination with 4 g prebiotic fructooligosaccharides	Dietary supplement: fortified synbiotic milk; 100 ml fortified (7,47 mg ferrous sulphate and 4,33 mg zinc acetate) synbiotic milk containing 7 billion CFU Lactobacillus plantarum Dad13 in combination with 4 g prebiotic fructooligosaccharides; Other Names: susu synbio (synbio milk) fortified
Placebo Comparator: non-fortified synbiotic milk; 100 ml non-fortified synbiotic milk containing 7 billion CFU Lactobacillus plantarum Dad13 in combination with 4 g prebiotic fructooligosaccharides	Dietary supplement: non-fortified synbiotic milk; 100 ml non-fortified synbiotic milk containing 7 billion CFU Lactobacillus plantarum Dad13 in combination with 4 g prebiotic fructooligosaccharides; Other Names: susu synbio (synbio milk) non-fortified

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Gut Microbiota Associated to Synbiotic Milk Treatment	Stools samples will be collected and analyzed before and after the intervention and compared between groups (Lactobacillus, Bifidobacteria, Bacteroides, Prevotella, and Enterobacteria) using qPCR method.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Height per Age Z-score Associated to Synbiotic Milk Treatment	Height data will be collected and analyzed before and after the intervention and compared between groups	3 months
Changes in Hemoglobin Level Associated to Synbiotic Milk Treatment	Hemoglobin data will be collected and analyzed before and after the intervention and compared between groups using biochemistry method	3 months
Changes in Calprotectin Level Associated to Synbiotic Milk Treatment	Calprotectin data will be collected and analyzed before and after the intervention and compared between groups using immuno-assay method	3 months
Changes in Blood Zinc Level Associated to Synbiotic Milk Treatment	Calprotectin data will be collected and analyzed before and after the intervention and compared between groups using Atomic Absorbance Spectrophotometry method	3 months
Changes in Cognitive Level Associated to Synbiotic Milk Treatment	Cognitive level will be collected and analyzed before and after the intervention and compared between groups using Bayley Scales of Infant Development, 2nd Edition (BSID). This part of BSID evaluation, which yields a score called the mental development index, evaluates several types of abilities: sensory/perceptual acuities, discriminations, and response; acquisition of object constancy; memory learning and problem solving; vocalization and beginning of verbal communication; basis of abstract thinking; habituation; mental mapping; complex language; and mathematical concept formation. Total score from test will determine mental development index of children : accelerated performance (score ≥85), within normal limit (score 70-84), mildly delayed performance (score 55-69), and significantly delayed performance (score <55).	3 months
Changes in Psychomotor Level Associated to Synbiotic Milk Treatment	Psychomotor data will be collected and analyzed before and after the intervention and compared between groups using Bayley Scales of Infant Development, 2nd Edition (BSID). This part of the BSID assesses the degree of body control, large muscle coordination, finer manipulatory skills of the hands and fingers, dynamic movement, postural imitation, and the ability to recognize objects by sense of touch (stereognosis). Total score from test will determine motor development index of children : accelerated performance (score ≥85), within normal limit (score 70-84), mildly delayed performance (score 55-69), and significantly delayed performance (score <55).	3 months

Collaborators and Investigators

• Sponsor: Gadjah Mada University
• Investigators: Principal Investigator: Siti Helmyati, DR., Gadjah Mada University; Principal Investigator: Lily A. Lestari, DR., Gadjah Mada University

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2018
• Primary Completion (Anticipated): September 30, 2018
• Study Completion (Anticipated): December 31, 2018

Study Registration Dates

• First Submitted: March 4, 2018
• First Submitted That Met QC Criteria: April 4, 2018
• First Posted (Actual): April 12, 2018

Study Record Updates

• Last Update Posted (Actual): May 1, 2018
• Last Update Submitted That Met QC Criteria: April 29, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Growth Disorders
• Other Study ID Numbers: KE/FK/0640/EC/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No