Mycotoxin Mitigation Trial
Condition: Aflatoxin Ingestion
Study type: Interventional

Summary: 
      Multiple observational studies show an association between fetal and post-natal aflatoxin
      exposure and reduced linear growth. However, the effects of confounding factors such as
      socio-economic status, food insecurity and nutrient deficiencies due to monotonous diets have
      not been ruled out. This trial will quantify the causal role of infant aflatoxin ingestion on
      post-natal growth by performing a cluster randomized trial in children 6-18 months of age in
      the Dodoma Region of Tanzania.

      All health facilities in one district in Dodoma will be randomized to the control or
      intervention arm. Infants will be recruited into the study over one year to account for
      seasonal variation in AF exposure. Both arms will receive infant and young child feeding
      education, a thermos flask and plastic measuring scoops. The intervention arm will receive a
      low-aflatoxin pre-blended porridge flour containing maize and groundnut (ratio 4:1
      respectively) and low-aflatoxin groundnut flour, whereas in the control arm the same porridge
      mix will be promoted through education, but acquired by the household. The primary outcome is
      length-for-age Z-score at 18 months.
    

Detailed description: 
      The objective of this study is to determine the effect of a very low AF complementary feeding
      intervention on LAZ using a cluster randomized design (CRT), while promoting a nutritionally
      adequate diet to all infants between 6-18 months of age. The hypothesis is that ingestion of
      AF can reduce infant length and that a reduction of AF exposure will result in improved
      length for age z-scores (LAZ). The primary outcome is LAZ, which will be measured at 18
      months.

      The unit of randomization is government-run health facilities (health centers, dispensaries
      and hospital, 52 clusters in total) in the Kongwa District. Mothers and infants will be
      recruited into the trial based on 42 day EPI visit attendance, which has very high (>95%)
      coverage in Kongwa District. Recruitment of infants will be performed for one complete
      calendar year capture variability in exposure by season.

      Critical to casual inference is the intervention's ability to create a contrast of AF
      consumption between the control and intervention groups, without creating differential macro-
      or micro-nutrient intake or differences in feeding and care practices that could affect
      stunting between arms. To reduce the risk of introducing these biases, the investigators
      designed the intervention to include: 1) education to improve infant feeding and care
      practices in both arms, and 2) behavior change communication on the use of blended infant
      porridge flours in both arms. Participants in the intervention group will receive
      low-aflatoxin blended infant porridge flour and groundnut flour, made in accordance with
      Tanzanian food and mycotoxin regulations. Those in the control group will not receive any
      flour, but will be advised to feed their infants a blend similar in ingredients and ratio to
      what the intervention group will receive. Both groups will receive a thermos flask to store
      porridge and a small plastic measuring scoop to measure porridge flour for preparation of the
      porridge.

      The sample size was calculated using a one-sided test of independent sample means, with a
      standard deviation of 1.2 Z, type I error of 0.05, power of 0.90, design effect of 2.0 and
      assuming a coefficient of variation of .144 for varying cluster size, based on previous
      year's data for EPI attendance at 42 days. Given these parameters our total sample size is
      calculated to be 2,322 (1,161 infants per cluster). Conservatively estimating a 20% loss to
      follow-up and infant mortality, the total number of infants is 2,787, or 54 infants recruited
      per health cluster annually or 4.5 infants per cluster per month. Rounding up, 5 infants per
      cluster each month will be recruited for a total of 3,120 potential infants, recognizing that
      in approximately 6 of the health facilities, it is unlikely that all 60 infants because of
      the size of the population served by the facility.

      The trial will be conducted in the Kongwa District of Dodoma, Tanzania, where the
      investigators have performed formative research (Protocol Identification#: 1703007043) and
      confirmed AF contamination in local foods, primarily groundnuts, and that infants are exposed
      to aflatoxin. The frequency and level of exposure is similar in range to the West African
      observational studies. Kongwa District is a good location to perform this study, as exposure
      is high enough to be suspected of contributing to stunting, but low enough as to not cause
      aflatoxicosis.

      NOTE: Data collection was stopped between April 9 and June 8, 2020 due to the SARS-CoV-2
      outbreak, in accordance with the guidance of the Tanzanian National Institute for Medical
      Research. The delivery of the intervention continued during this time.
    

Intervention name(s): Provision of flour; Promotion of flour
Intervention type(s): Other; Other
Intervention description(s): Infant and young child feeding education and provision of low AF porridge and groundnut flours from 6-18 months; Infant and young child feeding education and promotion of porridge and groundnut flours from 6-18 months
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Aflatoxin ingestion; Growth; Stunting, nutritional