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

• ClinicalTrials.gov Identifier: NCT03094247
• Recruitment Status: Completed
• First Posted: March 29, 2017
• Last Update Posted: July 19, 2022
• Sponsor: Washington University School of Medicine
• Collaborators: University of Texas at Austin; Cornell University; Kamuzu University of Health Sciences
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Severe Acute Malnutrition	Drug: Amoxicillin; Dietary Supplement: HO-RUTF; Dietary Supplement: D-HO-RUTF; Dietary Supplement: S-RUTF	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2897 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Improved Polyunsaturated Ready-to-use Therapeutic Food for Improved Neurocognitive Outcomes in Severe Acute Malnutrition
• Actual Study Start Date: October 2, 2017
• Actual Primary Completion Date: March 23, 2021
• Actual Study Completion Date: March 23, 2021

Arms and Interventions

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 Name: 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 Name: 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 Name: Amoxil; Dietary Supplement: D-HO-RUTF; D-HO-RUTF: DHA, milk, perilla oil, palm oil, white sugar, high oleic peanuts

Outcome Measures

Primary Outcome Measures :

1. Neurocognitive outcome [ Time Frame: Time Frame: 4 to 7 months after nutritional 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"
2. Neurocognitive outcome [ Time Frame: Time Frame: within 4 weeks after nutritional 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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 59 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Malawi

University of Malawi College of Medicine

Blantyre, Malawi

Sponsors and Collaborators

Washington University School of Medicine

University of Texas at Austin

Cornell University

Kamuzu University of Health Sciences

Investigators

• Study Chair: Mark J Manary, MD; Washington University School of Medicine

  Study Documents (Full-Text)

Documents provided by Washington University School of Medicine:

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] July 16, 2021

More Information

Study Data/Documents: Individual Participant Data Set 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03094247
• Other Study ID Numbers: MMPUFA17
• First Posted: March 29, 2017
• Last Update Posted: July 19, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Time Frame: Data will be available within 9 months of article publication. Data will remain available indefinitely.
• Access Criteria: Anyone who wishes to access the data.
• URL: https://openscholarship.wustl.edu/data/101/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Washington University School of Medicine:

Malnutrition; Micronutrients; Polyunsaturated fatty acids; Ready-to-use therapeutic foods; Omega-3 fatty acids; Peanuts

Additional relevant MeSH terms:

Malnutrition; Severe Acute Malnutrition; Nutrition Disorders; Amoxicillin; Anti-Bacterial Agents; Anti-Infective Agents