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

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.

Study Overview

• Status: Completed
• Conditions: Malnutrition, Child
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 1102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sierra Leone
  • Freetown, Sierra Leone
    • Project Peanut Butter Factory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 4 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RUSF skimmed milk powder; 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; ready-to-use supplementary foods 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients
Experimental: RUSF milk protein concentrate and sucrose; 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; ready-to-use supplementary foods 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients
Experimental: RUSF soy protein and whey permeate; 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; ready-to-use supplementary foods 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients
Experimental: RUSF soy and sucrose; 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; ready-to-use supplementary foods 75 kcal/kg/day (314 kJ/kg/day) and full daily doses of vitamins and micronutrients

What is the study measuring?

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 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
Sub-group analysis of %L and 16S rRNA outcomes among children not receiving breastfeeding at baseline vs. those being breastfeed at baseline	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
Metabolomic feature abundance in the 4 dietary groups	Metabolomic feature abundance in the 4 dietary groups, as determined by untargeted metabolomics in 200 randomly selected children with MUAC < 12.1 cm on enrollment	After 4 weeks of supplementary feeding

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Project Peanut Butter, Sierra Leone
• Investigators: Principal Investigator: Mark Manary, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Black RE, Allen LH, Bhutta ZA, Caulfield LE, de Onis M, Ezzati M, Mathers C, Rivera J; Maternal and Child Undernutrition Study Group. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet. 2008 Jan 19;371(9608):243-60. doi: 10.1016/S0140-6736(07)61690-0. No abstract available.
• Nackers F, Broillet F, Oumarou D, Djibo A, Gaboulaud V, Guerin PJ, Rusch B, Grais RF, Captier V. Effectiveness of ready-to-use therapeutic food compared to a corn/soy-blend-based pre-mix for the treatment of childhood moderate acute malnutrition in Niger. J Trop Pediatr. 2010 Dec;56(6):407-13. doi: 10.1093/tropej/fmq019. Epub 2010 Mar 23.
• Caulfield LE, de Onis M, Blossner M, Black RE. Undernutrition as an underlying cause of child deaths associated with diarrhea, pneumonia, malaria, and measles. Am J Clin Nutr. 2004 Jul;80(1):193-8. doi: 10.1093/ajcn/80.1.193.
• Shankar AH. Nutritional modulation of malaria morbidity and mortality. J Infect Dis. 2000 Sep;182 Suppl 1:S37-53. doi: 10.1086/315906.
• Matilsky DK, Maleta K, Castleman T, Manary MJ. Supplementary feeding with fortified spreads results in higher recovery rates than with a corn/soy blend in moderately wasted children. J Nutr. 2009 Apr;139(4):773-8. doi: 10.3945/jn.108.104018. Epub 2009 Feb 18.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Actual): March 7, 2022
• Study Completion (Actual): March 7, 2022

Study Registration Dates

• First Submitted: December 23, 2019
• First Submitted That Met QC Criteria: December 30, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Child Nutrition Disorders; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Caseins
• Other Study ID Numbers: 201912091

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No