Clinical trial NCT04874688: Child Health, Agriculture and Integrated Nutrition
Official title: Child Health, Agriculture and Integrated Nutrition (CHAIN): a Randomized Trial to Close the Nutrient Gap in Rural Zimbabwe
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Stunting
Keywords: Infant and young child feeding
Nutrients
Environmental enteric dysfunction
Microbiota
Immune function
Systemic inflammation
Metabolic profile
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
Collaborators: name: CIMMYT
name: University of Southampton
name: Ministry of Health and Child Welfare, Zimbabwe
First posted: 2021-05-06
Enrollment: 192
Sex: ALL
Minimum age (years): 5
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Individually randomized, unblinded clinical trial
Primary purpose: PREVENTION

Brief summary: CHAIN is an open-label, individually randomized trial of improved infant and young child feeding (IYCF) versus "IYCF-plus" among 192 infants enrolled between 5-6 months of age in Shurugwi district, rural Zimbabwe. Interventions comprise sequential behaviour-change interventions delivered by village health workers together with food supplements. In the IYCF arm, infants will receive white maize and small-quantity lipid-based nutrient supplement (SQ-LNS) daily from 6 months of age. In the IYCF-plus arm, infants will receive orange pro-vitamin A-biofortified maize, and SQ-LNS, plus powdered sugar beans, moringa and whole egg powder. The primary outcome will be the proportion of infants in each trial arm reaching daily energy requirements at 9 months of age (visit window 9-11 months of age). Secondary outcomes are other nutrient intake, anthropometry and haemoglobin. Tertiary outcomes are laboratory measures of microbiome composition, environmental enteric dysfunction, inflammation, innate immune function, circulating choline and essential amino acids, and urinary metabolic profile. Two qualitative substudies will explore i) the feasibility and acceptability of the IYCF-plus intervention; and ii) the influence of migration on household food consumption and production.

Detailed description: Linear growth failure (stunting) in childhood is the most prevalent form of undernutrition globally. Diets in rural sub-Saharan Africa have low dietary diversity and a reliance on white maize, which is high in starch and low in other nutrients. Improving infant and young child feeding (IYCF) during the period of complementary feeding from 6-24 months of age, including use of daily small-quantity lipid-based nutrient supplements (SQ-LNS), has a modest impact on linear growth. However, despite intensive IYCF interventions, infants often still have nutrient gaps. Furthermore, three key biological barriers (environmental enteric dysfunction, dysbiosis of the gut microbiota, and systemic inflammation) limit nutrient uptake and utilisation.

The overarching goal of this trial is to fill key nutrient gaps among infants in rural sub-Saharan Africa through an improved IYCF intervention using locally available foods that can ultimately be self-sustaining through agriculture. Addressing intake, uptake and utilization of nutrients in tandem, through use of 'functional foods' could ultimately improve growth and development in young children.

CHAIN is an open-label, individually randomized trial of improved infant and young child feeding (IYCF) versus "IYCF-plus" among 192 infants enrolled between 5-6 months of age in Shurugwi district, rural Zimbabwe. Interventions comprise sequential behaviour-change interventions delivered by village health workers together with food supplements. In the IYCF arm, infants will receive white maize and small-quantity lipid-based nutrient supplement (SQ-LNS) daily from 6 months of age. In the IYCF-plus arm, infants will receive orange pro-vitamin A-biofortified maize, and daily SQ-LNS, plus additional foods that are nutrient-rich, culturally acceptable and locally sustainable: NUA-45 biofortified sugar beans, moringa leaf powder and whole egg powder. For the duration of the trial, these foods will be provided as dried powders, which can be added to infant porridge as point-of-use fortificants. Together, these food supplements have the added plausible benefit of improving the microbiota and gut barrier function and reducing intestinal and systemic inflammation.

The primary outcome will be the proportion of infants in each trial arm reaching daily energy requirements at 9 months of age (visit window 9-11 months of age). Secondary outcomes are intake of protein, iron, zinc and folate; height-for-age Z score, weight-for-age Z-score, and weight-for-height Z-score; and haemoglobin. Tertiary outcomes are laboratory measures of microbiome composition, environmental enteric dysfunction, inflammation, innate immune function, circulating choline and essential amino acids, and urinary metabolic profile. Two qualitative substudies will explore i) the feasibility and acceptability of the IYCF-plus intervention; and ii) the influence of migration on household food consumption and production.

Trained research nurses will collect baseline data on maternal and infant demographics, nutritional status and household characteristics. Infants will have anthropometry measurements undertaken, and baseline infant stool, urine and blood samples will be collected by the research nurse.

All interventions are delivered by trained village health workers, each of whom has an allocated catchment area as part of their regular duties. VHW will provide regular interactive education modules for the IYCF and IYCF-plus arms, and deliver monthly supplies of food supplements from enrolment until 12 months of infant age. VHW will be overseen by a cadre of intervention nurses, who will provide supportive supervision, conduct spot checks, and hold meetings with the VHWs they supervise to ensure consistency in delivering the trial messages. In this way, the cadre delivering the interventions (VHW, supervised by intervention nurses) will be separated from the cadre measuring the trial outcomes (research nurses), to avoid courtesy bias among participants.

At the endline home visit at 9 months of infant age (window: 9-11 months) a research nurse will collect data by maternal recall on use of the IYCF or IYCF-plus supplements and on infant dietary intake by multi-pass 24-hour dietary recall. Infants will have repeat anthropometry undertaken, and urine, stool and blood samples collected, with point-of-care measurement of haemoglobin. A further visit will be undertaken 1 week later in 50% of households to repeat the 24-hour diet recall.

Laboratory analyses will include measures of environmental enteric dysfunction; microbiome composition; innate immune function; systemic inflammation; circulating choline and essential amino acids; and urinary metabolic profile.

To explore the feasibility and acceptability of the IYCF-plus intervention, one qualitative substudy will collect information from study households, the village health workers who support them, and key community stakeholders. Research findings will inform how this intervention can be rolled out at scale. Up to 20 households will be purposively sampled after the baseline survey. In-depth interviews will be conducted by a trained social scientist when the infant is 7-9 months old after the households have been introduced to all the nutrients (SQ-LNS and food powders), focused on household feeding practices and norms, household farming practices and related livelihood strategies, and the acceptability of the new supplements. Attention will also be focused on the influence of gendered norms and social relations on household decision-making practices in these areas.

To identify the influence of migration on household food consumption and production, a second qualitative substudy will enrol up to 30 participating households identified from the baseline questionnaire survey as having at least one family member who has migrated. In addition to exploring the impact of migration on household food consumption and production practices, the in-depth interviews conducted for this sub-study aim to investigate possible interactions between migration and household participation in the CHAIN intervention.

Eligibility criteria: Inclusion Criteria:

* Age between 5-6 months
* Planning to live in the study area for the duration of the trial

Exclusion Criteria:

* Severe infant disability that interferes with feeding
* Known allergy to peanuts or eggs

Primary outcomes:
measure: Energy intake
timeFrame: 9 months of age (window 9-11 months)
Secondary outcomes:
measure: Protein intake
timeFrame: 9 months of age (window 9-11 months)
measure: Iron intake
timeFrame: 9 months of age (window 9-11 months)
measure: Zinc intake
timeFrame: 9 months of age (window 9-11 months)
measure: Folate intake
timeFrame: 9 months of age (window 9-11 months)
measure: Height-for-age Z-score
timeFrame: 9 months of age (window 9-11 months)
measure: Weight-for-age Z score
timeFrame: 9 months of age (window 9-11 months)
measure: Weight-for-height Z score
timeFrame: 9 months of age (window 9-11 months)
measure: Haemoglobin
timeFrame: 9 months of age (window 9-11 months)
Other outcomes:
measure: Microbiome maturity
timeFrame: 9 months of age (window 9-11 months)
measure: Environmental enteric dysfunction
timeFrame: 9 months of age (window 9-11 months)
measure: Innate immune cell phenotype
timeFrame: 9 months of age (window 9-11 months)
measure: Innate immune cell function
timeFrame: 9 months of age (window 9-11 months)
measure: Plasma essential amino acids
timeFrame: 9 months of age (window 9-11 months)
measure: Plasma choline
timeFrame: 9 months of age (window 9-11 months)
measure: Urinary metabolic signature
timeFrame: 9 months of age (window 9-11 months)
Locations:
city: Harare
country: Zimbabwe
facility: Zvitambo Institute for Maternal and Child Health Research
Study officials:
affiliation: Zvitambo Institute for Maternal and Child Health Research
name: Laura E Smith, PhD
role: PRINCIPAL_INVESTIGATOR
References: