Clinical trial NCT03079583: The Efficacy of Zinc-biofortified Rice in Bangladeshi Children
Official title: The Efficacy of Zinc-biofortified Rice in Improving Zinc Status in Young Bangladeshi Children, a Double Blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Zinc Deficiency
Growth; Stunting, Nutritional
Keywords: Zinc Biofortification
Zinc Status
Zinc Biomarker
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
Collaborators: name: HarvestPlus
name: BRAC University
First posted: 2017-03-14
Enrollment: 520
Sex: ALL
Minimum age (years): 12
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Eligibility criteria: 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).

Primary outcomes:
measure: plasma zinc
timeFrame: 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 outcomes:
measure: Inflammatory markers
timeFrame: 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).
measure: Length
timeFrame: 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).
measure: Weight
timeFrame: 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).
measure: Morbidity
timeFrame: Fixed assessment once a week for every participant throughout the intervention period (week 1-36).
measure: FADS analyses
timeFrame: Secondary analyses of collected plasma samples, in subset of participants (75 children from each group, random selected, matched baseline and endpoint samples)
measure: Iron status
timeFrame: 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).
measure: Iron status
timeFrame: 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).
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: BRACU, Bangladesh
city: Zurich
country: Switzerland
facility: Swiss Federal Institute of Technology (ETH)
Study officials:
affiliation: Professor, Laboratory of Human Nutrition, Department of health science and technology, ETH Zurich, Zurich, Switzerland
name: Michael B Zimmermann, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Associate Professor, James P Grant school of Public Health, BRAC University, Dhaka, Bangladesh
name: Malay K Mridha, Assoc. Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.