Milk Matters in Malnutrition, is it the Lactose or Dairy Protein?

Study Overview
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Brief Summary
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This study is to look at the types of sugar and protein composition in the treatment of moderate acute malnutrition and its effects on gut health. The study will use 4 different types of ready to use supplementary foods to see which one if any has better recovery rate along with looking into the gut health. Children will be treated using one food for up to 12 weeks. A subset of about 400 will be tested for intestinal permeability using the dual sugar test.

Official Title
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Milk Matters in Malnutrition, is it the Lactose or Dairy Protein?

Conditions
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Malnutrition, Child

Intervention / Treatment
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* Dietary Supplement: RUSF skimmed milk powder
* Dietary Supplement: RUSF milk protein concentrate and sucrose
* Dietary Supplement: RUSF soy protein and whey permeate
* Dietary Supplement: RUSF soy and sucrose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MUAC < 12.5 cm and ≥ 11.5 cm without bipedal oedema Exclusion Criteria: If they are involved in another research trial in another supplemental feeding program debilitating illness history of peanut or milk allergy

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RUSF skimmed milk powder<br>RUSF will provide 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients. Caregivers will instruct caregivers to feed the supplement only to the enrolled child, to feed it in addition to their usual diet, and to use daily portions. | Dietary Supplement: RUSF skimmed milk powder<br>* ready-to-use supplementary foods 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients<br>|
| Experimental: RUSF milk protein concentrate and sucrose<br>RUSF will provide 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients. Caregivers will instruct caregivers to feed the supplement only to the enrolled child, to feed it in addition to their usual diet, and to use daily portions. | Dietary Supplement: RUSF milk protein concentrate and sucrose<br>* ready-to-use supplementary foods 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients<br>|
| Experimental: RUSF soy protein and whey permeate<br>RUSF will provide 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients. Caregivers will instruct caregivers to feed the supplement only to the enrolled child, to feed it in addition to their usual diet, and to use daily portions. | Dietary Supplement: RUSF soy protein and whey permeate<br>* ready-to-use supplementary foods 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients<br>|
| Experimental: RUSF soy and sucrose<br>RUSF will provide 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients. Caregivers will instruct caregivers to feed the supplement only to the enrolled child, to feed it in addition to their usual diet, and to use daily portions. | Dietary Supplement: RUSF soy and sucrose<br>* ready-to-use supplementary foods 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % lactulose excretion after 4 weeks of supplementary feeding | This will only be assessed in children with higher-risk (MUAC < 12 cm) MAM at baseline. %L measured in the urine relative to the amount ingested will be calculated. %L will be categorized as normal (<0.2%) and abnormal (>0.2) | 4 weeks | 
| 16S rRNA relative abundance of bacterial taxa after 4 weeks of supplementary feeding | This will only be assessed in children with higher-risk (MUAC < 12 cm) MAM at baseline | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of weight gain (g/kg/d) | Changes in weight relative to baseline weight | up to 12 weeks of treatment | 
| Rate of length gain (mm/week) | Changes in linear growth | up to 12 weeks of treatment | 
| Final mid-upper arm circumference | Use the mid-upper are circumference at the visit when outcome was reached | up to 12 weeks of treatment | 
| Proportion with %L < 0.20 | Percentage of children with %L excreted < 0.20 | 4 weeks | 
| 16S rRNA beta-diversity at week 4 | Looking at the 16S configuration in stool samples collected | 4 weeks | 
| 16S rRNA alpha-diversity at week 4 | Several metrics of alpha diversity will be assessed, including Shannon's index | 4 weeks | 
| Rate of recovery from moderate acute malnutrition | Recovery is when a participant reaches a Mid-Upper Arm Circumference of 12.5cm or better | up to 12 weeks of treatment | 
| Rate of deteriorating to severe acute malnutrition or death | Severe acute malnutrition defined by MUAC < 11.5 cm or development of nutritional edema | up to 12 weeks of treatment | 
| Sub-group analysis of %L and 16S rRNA outcomes among children not receiving breastfeeding at baseline vs. those being breastfeed at baseline | o Anthropometric, %L and 16s rRNA outcomes (relative abundance, alpha-diversity, beta-diversity) will be compared between study foods among those who are reported to be breastfeeding vs. those who are not | 4 weeks | 
| Sub-group analysis of anthropometric outcomes among children with MUAC < 12 cm vs. >= 12 cm at baseline | Rate of weight change, length change, final MUAC, recovery, SAM, and death will be compared between the study foods among children with baseline MUAC < vs. >=12 cm. | up to 12 weeks of treatment |