Clinical trial NCT03181178: Effect of a Complementary Food Supplement on Growth and Morbidity of Ghanaian Infants
Official title: Effect of a Complementary Food Supplement on Growth and Morbidity of Ghanaian Infants (6 to 18 Months)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Growth Disorders
Infant Malnutrition
Micronutrient Deficiency
Protein Malnutrition
Morbidity;Infant
Keywords: Complementary food supplement
Protein quality and linear growth
Intervention targeting complementary foods and growth
Lead sponsor: Nevin Scrimshaw International Nutrition Foundation
Sponsor class: OTHER
Collaborators: name: University of Ghana
name: University of Cape Coast
name: Ajinomoto USA, INC.
name: Ghana Health Services
First posted: 2017-06-08
Enrollment: 1204
Sex: ALL
Minimum age (years): 6
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study has three intervention arms and one cross sectional growth monitoring follow up group.
Primary purpose: PREVENTION

Brief summary: Prevention of malnutrition in infants and children requires access and intake of nutritious food starting at birth with exclusive breastfeeding for the first 6 months of life, breastfeeding in combination with complementary foods from 6-24 months of age, access to clean drinking water and sanitation, access to preventive and curative health care (including prenatal).

In Ghana, the Demographic and Health Survey of 2014 reports rates of stunting, wasting and underweight in children aged 0-59 months are 28%, 14% and 9% respectively. Furthermore, height for age starts dropping from age 4-6 months with children aged 6-23 months being more likely to be stunted (40%) than those below 6 months (4%). Infant and young child feeding data show that for breast-fed children ranging from 6 months through 35 months of age, cereals are predominantly the first foods introduced in the diet (6-8 months of age). As the child grows older, consumption of fruits rich in Vitamin A, other fruits and vegetables and meat, fish, poultry and eggs are reported by the mothers. The Demographic and Health Survey (DHS) found that the proportion of breast fed children aged 6-23 months who received a recommended variety of foods the minimum number of times per day increases with child's age from 28% in children 6-8 months to 50% in children aged 18-23 months.

The study objective is to examine the effect of providing a macro- and micro-nutrient fortified complementary food supplement (KokoPlusTM) on growth and nutritional status of Ghanaian infants.

Detailed description: The current study is a cluster randomized single blind intervention design study with three study arms that aimed to examine the effect of providing a macro- and micro-nutrient fortified complementary food supplement (KokoPlus) for a period of 12 months (starting at 6 months of age) on growth and nutritional status of Ghanaian infants at 18 months of age. KokoPlus was formulated using linear programming methodology based on formative and market analysis research findings.

The subjects in this cluster-randomized trial are from communities in three districts of the Central region in Ghana with high rates of moderate and severe acute malnutrition. A total of 38 communities will be randomly assigned to one of three groups using block randomization and another 11 (randomly selected) will be followed cross sectionally as part of a fourth/non intervention group (growth monitoring).

The total sample size is 1204. Sample size calculations were based on two outcome measures: expected reduction in diarrheal morbidity and growth (improvements in height-for-age). Sample size estimates for detecting a 0.5 cm change in height in children provided a caloric and non caloric micronutrient supplement using a design effect of 2, power of 0.80, alpha of 0.05 and assuming an attrition rate of 15%, the required sample size per group was 301.

Mother-infant pairs will be recruited between infant age of 0 to 3 months to participate in monthly nutrition educations sessions and to encourage the women to continue exclusive breast feeding across all three groups. At 6 months of age, infants in each of the three groups were enrolled into the intervention study (upon receipt of informed consent). Data collection involves baseline, midline and endline measurements in the infants at 6, 12 and 18 months of age. In addition, participating mother-infant pairs will be visited weekly for delivery of the supplements and for morbidity monitoring and monthly for the measurement of anthropometry. Anthropometric measurements include: length (Infant/Child Shorr Height Board; Weigh and Measure, LLC ), weight (Seca 874 digital scale ), mid-upper arm circumference (MUAC) (Child MUAC Tape; Weigh and Measure, LLC), subscapular and triceps skinfolds (Holtain skinfold caliper ),head and chest circumference.

Data collection at baseline, midline and endline included one venous sample (3ml) from the infant, HemoCue (Model 301) measurement to assess severe anemia (7 \<g/dl) with appropriate referrals as mentioned earlier. Ethylenediaminetetracetic acid (EDTA) Vacutainers (BD ; catalog number 368841) for whole blood and plasma analyses and Trace Element Serum Separator Tube Vacutainers (BD; catalog number 368380) for serum analyses will be used for the sample collection with butterfly needles (21 or 23 gauge). Samples will be immediately placed in a super cooler tube rack and transported back to the lab within five hours where they were processed immediately. Questionnaires will be administered to assess socio-economic status, infant and young child feeding practices, morbidity (past week), household food security along with a 24 hour diet recall. Data was uploaded daily through cellular network, stored on Formhub and then Ona organization servers.

The primary outcome of the study is the change in length for age Z-score from 6 to 18 months of age in infants in the KokoPlus group versus Micronutrient powder group and the Nutrition Education group. Data calculations included estimating anthropometric indices using the WHO (World Health Organization) 2006 growth reference charts using the WHO macro in STATA (18), computing the USAID Food and Nutrition Technical Assistance (FANTA) household insecurity access scores (HFIAS) (19) maternal body mass index (BMI), dietary diversity scores (20), and re-coding variables as required to binary and accounting for missing. Infant anthropometric indices calculated include length for age (LAZ) Z- score, weight for age Z-score (WAZ) and weight for length (WLZ score).

All analyses are intent to treat. Descriptive statistics (means, medians, standard deviations and standard errors) were computed. To verify the randomization assumption, any differences in mean values at baseline across three groups were tested using linear mixed effects regression analyses accounting for clustering. The effect of the supplement (KokoPlus, Micronutrients and Nutrition Education group) on different dependent variables across the intervention period will be tested using mixed effects regression analyses accounting for clustering and repeated measures. The dependent variables tested included change in LAZ between baseline and endline (primary outcome), change in LAZ on a monthly basis (primary outcome 2), change in WAZ, WLZ, serum hemoglobin (unadjusted and adjusted for inflammation), serum ferritin (unadjusted and adjusted for inflammation), serum zinc, serum cortisol, serum insulin growth factor-1 (IGF-1), serum retinol binding protein, C-reactive protein and alpha glycoprotein, prevalence of acute and chronic infection.

A cross-sectional assessment (anthropometry) will be conducted at baseline, midline and endline in 301 infants that are randomly selected from another set of communities (to be identified based on the same community selection criteria). These infants will not be followed longitudinally and the only measurements to be collected include weights and heights. Informed consent procedures will be similar to the three intervention arms. This group is a reference group only and cannot be included in any comparative analysis.

Monitoring of groups that receive a supplement will happen weekly. Compliance will be defined based on the number of supplement packets that are consumed per week. To assure that the mothers are compliant in using the supplement, they will be asked to return the empty supplement packages at the end of the week. Optimal compliance will be defined as consumption of at least 50% of the weekly samples. Supplements will be provided in plastic or paper bags with a clearly labelled household ID (identity number). Compliance and dose response to compliance will be reviewed in existing studies to determine minimum compliance required.

Eligibility criteria: Inclusion Criteria:

1. Non pre-term
2. Singleton birth
3. Exclusively or predominantly breast fed up to time of recruitment
4. Parents planning to live in community for a period of 12 months and willing to participate in the trial for the entire period
5. Receive informed consent from both parents and/or caregivers or from mother alone if single

Exclusion Criteria:

1. Severely anemic (\<7 g/dl) (to be referred to Community Health Post (CHP) for routine care on anemia as recommended by Ghana Health Service)
2. Severely malnourished (MUAC \<110 mm) (to be referred to CHP with Community-based Management of Acute Malnutrition (CMAM) protocol) and/or use of CMAM protocol or below -2 standard deviations (SD) weight for age Z score

Primary outcomes:
measure: Change in monthly length for age Z-score (monthly LAZ)
timeFrame: Measured on a monthly basis until 18 months of age
Secondary outcomes:
measure: Change in Serum Hemoglobin
timeFrame: Baseline (6 months), Midline (12 months of age), Endline (18 months of age)
measure: Change in Serum retinol binding protein
timeFrame: Baseline (6 months), Midline (12 months of age), Endline (18 months of age)
measure: Change in serum transferrin receptors
timeFrame: Baseline (6 months), Midline (12 months of age), Endline (18 months of age)
measure: Change in serum ferritin
timeFrame: Baseline (6 months), Midline (12 months of age), Endline (18 months of age)
measure: Change in serum zinc
timeFrame: Baseline (6 months), Midline (12 months of age), Endline (18 months of age)
measure: Change in Weight for age Z-score
timeFrame: Measured at baseline and then on a monthly basis for the duration of the intervention (12 months)
measure: Change in Weight for height Z-score
timeFrame: Measured at baseline and then on a monthly basis for the duration of the intervention (12 months)
measure: Prevalence of diarrhea
timeFrame: Measured at baseline and then in a weekly surveillance for the duration of the intervention (12 months or 52 weeks)
measure: Prevalence of upper respiratory infections
timeFrame: Measured at baseline and then in a weekly surveillance for the duration of the intervention (12 months or 52 weeks)
measure: Change in serum C-reactive protein
timeFrame: Baseline (6 months), Midline (12 months of age), Endline (18 months of age)
measure: Change in serum alpha glycoprotein
timeFrame: Baseline (6 months), Midline (12 months of age), Endline (18 months of age)
measure: Change in Head Circumference for age
timeFrame: Measured at baseline and then on a monthly basis for the duration of the intervention (12 months)
measure: Change in MUAC (Mid Upper Arm Circumference)
timeFrame: Measured at baseline and then on a monthly basis for the duration of the intervention (12 months)
measure: Change in Plasma Amino Acid levels
timeFrame: Baseline (6 months), Midline (12 months of age), Endline (18 months of age)
Other outcomes:
Locations:
Study officials:
affiliation: Nevin Scrimshaw International Nutrition Foundation
name: Shibani Ghosh, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ghana
name: Gloria Otoo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ghana
name: Kwaku Tano-Debrah, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Pee S, Bloem MW. Current and potential role of specially formulated foods and food supplements for preventing malnutrition among 6- to 23-month-old children and for treating moderate malnutrition among 6- to 59-month-old children. Food Nutr Bull. 2009 Sep;30(3 Suppl):S434-63. doi: 10.1177/15648265090303S305.
citation: Pan American Health Organization. Guiding Principles for Complementary Feeding of the Breast Fed Child p37, 2003
citation: Ghana Statistical Service, Ghana Health Service, ICF Macro Ghana Demographic and Health Survey 2008, Accra, Ghana, p 512, 2009
citation: Furuta C, Sato W, Murakami H, Suri DJ, Otoo GE, Tano-Debrah K, Ghosh SA. Changes of Plasma Amino Acid Profiles in Infants With a Nutrient-Fortified Complementary Food Supplement: Evidence From a 12-Month Single-Blind Cluster-Randomized Controlled Trial. Front Nutr. 2021 Sep 30;8:606002. doi: 10.3389/fnut.2021.606002. eCollection 2021.