Feeding Malnourished Children Different Types of Fatty Acids to Promote Neurocognitive Development

Improved Polyunsaturated Ready-to-use Therapeutic Food for Improved Neurocognitive Outcomes in Severe Acute Malnutrition

An appropriate balance of omega-6 and omega-3 fatty acids is important for support of neurocognitive development in healthy infants and toddlers. In young children recovering from severe acute malnutrition (SAM), excess omega-6 intake depletes omega-3 fatty acid status. This research will evaluate how novel ready-to-use therapeutic foods (RUTF) with balanced fatty acids improve the metabolic and neurocognitive effects in young children in Malawi recovering from SAM, yielding new knowledge that also has implications for development of well-nourished children.

Study Overview

• Status: Completed
• Conditions: Severe Acute Malnutrition
• Intervention / Treatment: Drug: Amoxicillin; Dietary supplement: S-RUTF; Dietary supplement: HO-RUTF; Dietary supplement: D-HO-RUTF

• Study Type: Interventional
• Enrollment (Actual): 2897
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malawi
  • Blantyre, Malawi
    • University of Malawi College of Medicine

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 6-59 months
• An acceptable appetite defined by the ability to consume 30 grams RUTF within 20 minutes
• Mid Upper Arm Circumference <11.5 cm, weight-for-height z-score < -3, or bilateral pitting edema on the dorsum of the feet

Exclusion Criteria:

• Participation in any other ongoing study or supplementary feeding program
• Children with a chronic medical condition, including cerebral palsy, static encephalopathy, congenital heart disease, gastrointestinal disease, or peanut allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Conventional RUTF (S-RUTF); This is the control group for the study, which will receive the international standard of care therapeutic food. S-RUTF is made with conventional peanuts, which are inherently high in omega-6 linoleic acid.	Drug: Amoxicillin; All patients with severe acute malnutrition will receive a course of amoxicillin.; Other Names: Amoxil; Dietary supplement: S-RUTF; S-RUTF: Milk, canola oil, palm oil, white sugar, standard peanuts
EXPERIMENTAL: High oleic RUTF (HO-RUTF); The treatment provided to children randomized to this arm of the study includes nutritional content comparable to S-RUTF with the exception of a low lineoleic acid/high oleic acid ratio formulated with high oleic content peanuts.	Drug: Amoxicillin; All patients with severe acute malnutrition will receive a course of amoxicillin.; Other Names: Amoxil; Dietary supplement: HO-RUTF; HO-RUTF: Milk, perilla oil, palm oil, white sugar, high oleic peanuts
EXPERIMENTAL: DHA-supplemented HO-RUTF (D-HO-RUTF); The treatment provided to children randomized to this arm of the study mirrors that provided by HO-RUTF with that addition of supplemental DHA at a level higher than attainable with optimal precursors.	Drug: Amoxicillin; All patients with severe acute malnutrition will receive a course of amoxicillin.; Other Names: Amoxil; Dietary supplement: D-HO-RUTF; D-HO-RUTF: DHA, milk, perilla oil, palm oil, white sugar, high oleic peanuts

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive outcome	Measured by score on the Malawian Developmental Assessment Test (MDAT). The scale is continuous and interval in nature, the range varies by population; The scale title is "Malawi Developmental Assessment Tool z-score"; The primary outcome is Global z-score, titled "Global z-sore"; Secondary outcomes are 4 sub-domain z-scores are titled "Gross motor z-score", "Fine motor z-score", Language z-score", and "Social z-score"	Time Frame: 4 to 7 months after nutritional outcome
Neurocognitive outcome	Defined by Willatts intention score adapted for field training, 3 problems to be tested. The scale is ordinal in nature, with higher values indicated better scores; The scale title is "Intention Score"; Problem 1 is scored 0 - 4; Problem 2 is scored 0 - 4; Problem 3 is scored 0 - 8	Time Frame: within 4 weeks after nutritional outcome

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nutritional recovery	Defined by resolution of edema AND mid-upper arm circumference [MUAC] >12.4cm, AND/OR a weight/height z-score [WHZ] >-3	Up to 12 weeks following enrollment
Attentional orienting speed	Measured by mean saccade latency to peripheral targets	4-7 months after nutritional after nutritional outcome
Adverse Events	Measured by number of days diarrhea and/or rashes.	Fortnightly follow up visits up to 12 weeks following enrollment
Acceptance of RUTF	Mother's report of if the child ate the food well. This is a yes or no question.	Fortnightly follow up visits up to 12 weeks following enrollment

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Cornell University; Kamuzu University of Health Sciences; University of Texas at Austin
• Investigators: Study Chair: Mark J Manary, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• Stephenson K, Callaghan-Gillespie M, Maleta K, Nkhoma M, George M, Park HG, Lee R, Humphries-Cuff I, Lacombe RJS, Wegner DR, Canfield RL, Brenna JT, Manary MJ. Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: a randomized, triple-blinded, controlled clinical trial. Am J Clin Nutr. 2022 May 1;115(5):1322-1333. doi: 10.1093/ajcn/nqab363. Erratum In: Am J Clin Nutr. 2022 May 1;115(5):1442.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 2, 2017
• Primary Completion (ACTUAL): March 23, 2021
• Study Completion (ACTUAL): March 23, 2021

Study Registration Dates

• First Submitted: March 23, 2017
• First Submitted That Met QC Criteria: March 23, 2017
• First Posted (ACTUAL): March 29, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 14, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Micronutrients; Omega-3 fatty acids; Malnutrition; Polyunsaturated fatty acids; Peanuts; Ready-to-use therapeutic foods
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Severe Acute Malnutrition; Anti-Infective Agents; Anti-Bacterial Agents; Amoxicillin
• Other Study ID Numbers: MMPUFA17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the article after deidentification will be indefinitely available within 9 months following article publication through The Washington University Open Scholarship Institutional Repository.
• IPD Sharing Time Frame: Data will be available within 9 months of article publication. Data will remain available indefinitely.
• IPD Sharing Access Criteria: Anyone who wishes to access the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Study Data/Documents

1. Individual Participant Data Set

Drug and device information, study documents

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