The Efficacy of Zinc-biofortified Rice in Bangladeshi Children (ZARI)

The Efficacy of Zinc-biofortified Rice in Improving Zinc Status in Young Bangladeshi Children, a Double Blind Randomized Controlled Trial

To assess the efficacy of the zinc biofortified rice on plasma zinc concentrations in infants from a rural area of Bangladesh.

Study Overview

• Status: Completed
• Conditions: Zinc Deficiency; Growth; Stunting, Nutritional
• Intervention / Treatment: Dietary supplement: Control-group; Dietary supplement: Intervention-group

Detailed Description

Rationale: Around the world and estimated 30% of the population is at risk of Zinc deficiency, mainly due to monotonous plant base diets and the poor bioavailability of this sources. One staple food crop which is low in zinc content is rice. Therefore, zinc deficiency is highly common in Asia. Zinc plays a major role in child growth and neurobehavioral development. Furthermore, it is linked to infection control and normal immune response. One way to add extra zinc to someone's diet is zinc bio fortification of staple crops, which can be a cost saving sustainable approach to improve zinc nutrition. However, data on long-term intake of biofortified crops with zinc is scarce and efficacy of newly developed rice crops high in zinc are not well known.

Objective: The objective is to assess the efficacy of a newly developed zinc biofortified rice variety on plasma zinc concentrations in children in a rural area of Bangladesh when compared to their controls in a 9 month randomized controlled trial (RCT).

Study design: A double randomized control trial. Study population: Stunted children whom are zinc deficient at start of the study intervention determined by plasma zinc levels <9.9 µmol/L.

Main study parameters/endpoints: The difference in zinc status between the intervention and control group expressed in blood plasma zinc levels. Plasma zinc will be measured 4 times during the intervention period. Besides plasma zinc other zinc biomarkers will be tested for their usefulness.

• Study Type: Interventional
• Enrollment (Actual): 520
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • BRACU, Bangladesh
• Switzerland
  • Zurich, Switzerland, 8092
    • Swiss federal institute of Technology (ETH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 3 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 12-36 months of age (at baseline assessment)
• Low plasma Zn concentration (<10.71 µmol/L)
• Marginally stunted (height for age Z-score <-1.75)
• The informed consent form has been read and signed by the caregiver (or has been read out to the caregiver in case of illiteracy)

Exclusion Criteria:

• Severe Anemia (Hb< 70 g/L)
• Chronic or acute illness or other conditions that in the opinion of the Principle Investigator (PI) or co-researchers would affect Zn metabolism or would render the participant unable to comply with the protocol (based on self-reporting or diagnosed during screening)
• Participants taking part in other studies requiring the drawing of blood
• Not planning long-term residence in study site
• Regular intake (>2 days) of iron-containing mineral and vitamin supplements or fortified foods within the last 2 months
• Chronic use of drugs that affect the metabolism of Zn, including reducing absorption or increasing excretion; e.g., tuberculosis medications (ethambutal and isoniazides), drugs used as treatment for entamoeba hystolica (diiodohydroxyquin), drugs that reduce stomach acidity (H2 blockers and proton pump inhibitory), antidepressants (nialamide and socarboxazid), anti-inflammatory drugs (corticosteroids), diuretics (thiazides).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control-group; Control Rice used for meal, normal zinc level	Dietary supplement: Control-group; Control Rice with normal zinc levels
Active Comparator: Intervention-group; Biofortified Rice used for meal, around 30% higher zinc level	Dietary supplement: Intervention-group; Biofortified Rice is grown by foliar Zn application

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma zinc	Change of plasma zinc values from baseline to endpoint and 2 times within study period	4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory markers	C reactive protein (CRP),alpha1-acid glycoprotein (AGP)	4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3).
Length	Length (in cm) measurement for anthropometric (HAZ-scores).	4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3).
Weight	Weight (in kg) measurement for anthropometric (HAZ-scores).	4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3).
Morbidity	diarrhea and disease episodes will be recorded weekly throughout the study	Fixed assessment once a week for every participant throughout the intervention period (week 1-36).
FADS analyses	FADS plasma analyses for zinc biomarker determination	Secondary analyses of collected plasma samples, in subset of participants (75 children from each group, random selected, matched baseline and endpoint samples)
Iron status	Plasma ferritin	4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3).
Iron status	Hemoglobin	4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3).

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology
• Collaborators: BRAC University; HarvestPlus
• Investigators: Principal Investigator: Michael B Zimmermann, Prof. Dr., Professor, Laboratory of Human Nutrition, Department of health science and technology, ETH Zurich, Zurich, Switzerland; Principal Investigator: Malay K Mridha, Assoc. Prof., Associate Professor, James P Grant school of Public Health, BRAC University, Dhaka, Bangladesh

Publications and helpful links

General Publications

• Jongstra R, Hossain MM, Galetti V, Hall AG, Holt RR, Cercamondi CI, Rashid SF, Zimmermann MB, Mridha MK, Wegmueller R. The effect of zinc-biofortified rice on zinc status of Bangladeshi preschool children: a randomized, double-masked, household-based, controlled trial. Am J Clin Nutr. 2022 Mar 4;115(3):724-737. doi: 10.1093/ajcn/nqab379.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Actual): April 25, 2019
• Study Completion (Actual): April 25, 2019

Study Registration Dates

• First Submitted: March 3, 2017
• First Submitted That Met QC Criteria: March 8, 2017
• First Posted (Actual): March 14, 2017

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 16, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Zinc Biofortification; Zinc Status; Zinc Biomarker
• Additional Relevant MeSH Terms: Pathologic Processes; Growth Disorders
• Other Study ID Numbers: ZARI_1_trail

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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