Clinical trial NCT02479815: Impact of Low Dose Iron-containing Micronutrient Powders on Iron Status and Morbidity of Young Children in Ethiopia
Official title: Assessing the Safety of Iron Supplementation in Micronutrient Powder (MNPs)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nutritional Anemia
Infant Morbidity
Keywords: Complementary feeding recommendation
Program evaluation
Process and impact evaluation
Micronutrient powder (MNP) safety
Lead sponsor: Ethiopian Public Health Institute
Sponsor class: OTHER_GOV
Collaborators: name: Micronutrient Initiative
name: Wageningen University
First posted: 2015-06-24
Enrollment: 2356
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to assess the safety of iron supplementation in MNPs. A quasi-experimental matched-control cluster design will be used in, purposely selected, 18 intervention and 18 matched-control clusters of Oromia and South Nations Nationalities and People (SNNP) regions of Ethiopia. A total of 2340 infants 6-11 months of age, from intervention and non-intervention clusters will be enrolled and followed longitudinally for 12 months. Morbidity data using standardized questionnaire, will be collected at baseline, and every two weeks for a period of 12 months

Research questions to be answered in this study are:

1. Is the provision of low dose iron-containing Micronutrient Powders (MNPs) to young children with or without iron deficiency safe, as assessed by their morbidity from infectious diseases?
2. What is the impact of the provision of low dose iron-containing Micronutrient Powders (MNPs) to young children on (body) iron status? Morbidity data will be collected at baseline, and every two weeks in the same cohort of children.

Body iron status will be assessed at baseline and endline as measured by serum ferritin, serum transferrin receptor, hemoglobin concentration, CRP and AGP.

In addition data on the following outcomes will be collected in these children:

1. Anthropometry (weight, height, MUAC) every 4 months
2. Breastfeeding status and consumption of processed complementary food portions in the previous week -every 4 months
3. Compliance to study intervention.

Detailed description: For morbidity assessment 65 eligible children per cluster (18 intervention and 18non-intervention villages) a total of 2340 will be randomly selected The sample size was calculated based on an expected 12% increase in the incidence of overall diarrhoea and 30% decrease in anemia in the intervention group. The investigators assume that the investigators will be able to detect this increase with 80% power and 95% confidence interval, with an assumed 10% drop-out and design effect of two.

* Morbidity from infectious diseases will be assessed by means of a standardized recall questionnaire. Data will be collected on the following symptoms: diarrhea, respiratory signs, fever and other illnesses. Children who require medical treatment will be examined by a Health Officer at the health center following standard protocols of the Federal Ministry of Health.
* Biochemical iron status will be assessed from non-fasting venous morning blood samples. Blood samples will be kept cool and serum separated and frozen at -20oC within 3 hours of collection. Hemoglobin, serum ferritin, C-reactive protein (CRP), soluble transferrin receptor and AGP will be assessed following standardized methodologies at the laboratories of the Ethiopian Public Health Institute (EPHI).
* Anthropometry: Trained field staff will collect duplicate measurements every four months of weight, recumbent length (infants) and height (children \> 12 months) using standardized methods and high quality equipment. Z-scores for length-for-age (LAZ), weight-for-age (WAZ) and weight-for-length (WLZ) will be calculated, using the 2006 WHO Child Growth Standard; and stunting, under-weight and wasting will be defined as LAZ, WAZ and LAZ \<-2 SD, respectively.
* Infant feeding status. Information on infant feeding status will be collected every four months by means of a standardized questionnaire.
* Compliance to the program intervention: will be assessed by counting the number of returned and used MNP sachets every 2 weeks.
* Social, economic and demographic characteristics: will be collected in baseline questionnaires using Demographic and Health Survey methods.

Data will be analysed on an intention-to-treat basis, using the SPSS 19.0 statistical program. Random effect models will be used to account for repeated measures or episodes within children, and multiple children in each cluster.

For morbidity, the number of actual surveillance days will be counted by subtracting the days on which no recall data were available from the total days of follow-up. For the analysis of disease incidence, differences between groups will be assessed with random effects regression including number of episodes as dependent, control- or intervention as independent, and total days of actual surveillance as off-set term in the model. Longitudinal prevalence of disease will be calculated for each individual as the percentage of actual surveillance days with illness. All continuous variables (longitudinal prevalence, body iron status, mean and total weight and height gain) will be analysed using linear mixed models using cluster, household and child as random effects to account for clustered observations. Mixed effects logistic regression analysis will be used to evaluate binary outcomes (anemia, iron deficiency and iron-deficiency anemia), using cluster, household and child as random effects. All models will include the following fixed effects as co-variates: child's sex, socio-economic status, and baseline values. Non-normal distributed values will be log-transformed. P-values of \< 0.05 will be considered statistically significant.

Eligibility criteria: Inclusion Criteria:

* Living in one of the selected intervention and non-intervention villages
* Between 6 months and 11.99 months old at the day of recruitment
* Have not yet been provided with MNPs as part of the project interventions
* Free of chronic conditions that may impact their health
* Caregivers do not plan to migrate out of the study area
* Caregivers have provided written informed consent for this additional safety component

Exclusion Criteria:

* Children who are severely malnourished (Wt/Ht Z-score \< -3 SD) will be referred to treatment and excluded from the safety component
* Children with a chronic disease and/or chronic use of medications
* Children who are severe anemic (Hb\< 70 g/L)

Primary outcomes:
measure: Anemia
timeFrame: Baseline and Endline
measure: % of new acute diarrhea episodes (>3 loose stools/day) per 52 surveillance weeks
timeFrame: Up to one year
Secondary outcomes:
measure: Iron status
timeFrame: Baseline and Endline
measure: % of new respiratory infection episodes (cough and/or difficult breathing with or without fever, accompanied by rapid breathing and chest in drawing) per 52 surveillance weeks
timeFrame: Up to one year
measure: Prevalence of Fever
timeFrame: Up to one year
measure: Growth
timeFrame: Up to one year
Other outcomes:
Locations:
city: Addis Ababa
country: Ethiopia
facility: Ethiopian Public Health Institute
Study officials:
affiliation: Micronutrient Initiative
name: Saskia JM Osendarp, PhD
role: STUDY_CHAIR
affiliation: Wageningen University
name: Inge D Brouwer, PhD
role: STUDY_DIRECTOR
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