Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
NA
1500 participants
INTERVENTIONAL
2023-12-05
2026-06-30
Brief Summary
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\- Will the addition of a 500mg daily dose of choline to RUTF during treatment for SAM improve cognitive development among 6-59-month-old Malawian children compared with standard RUTF without added choline?
Detailed Description
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Ready-to-use therapeutic food (RUTF) revolutionized SAM treatment by allowing it to occur in the home setting. RUTF cures most children with SAM and ameliorates many of its worst consequences. RUTF was designed to be food-safe and promote anthropometric recovery. Since its inception, evidence has accumulated suggesting that the original fatty acid content of RUTF was not optimized for cognitive recovery from SAM. A 2021 trial, the Improved PUFA Trial (PMID: 34726694), demonstrated that reducing the omega-6 fatty acid content of RUTF and adding docosahexaenoic acid (DHA) improved cognitive development 6 months after SAM treatment in Malawian children. It is possible that further modifications to RUTF's composition might promote greater cognitive recovery.
Choline is essential for human health and development and is recognized as such by the Institute of Medicine, which designates daily recommended intakes. Choline deficiency has been shown to induce a host of cognitive developmental problems in animal models, is associated with neural tube defects in humans, and mutations of choline transporters in humans yield developmental degenerative conditions which, while rare, shed light on the essential nature of choline in brain development. Several small randomized, controlled trials have shown benefits of choline supplementation during early life on child cognitive development, both in healthy children and in those exposed to insults such as in fetal alcohol syndrome.
Choline plays important roles in brain structure and function and is found primarily in animal-source foods, which are deficient in the diets of children with SAM. Choline is an essential component of the neuronal membrane as well as a precursor for acetylcholine, a key neurotransmitter. In addition, choline plays a role in the trafficking and cell membrane integration of DHA, which rapidly accumulates in the human brain during childhood and ultimately composes 40-50% of brain polyunsaturated fatty acids. Decades of findings from epidemiological studies and laboratory science, including with animal models, support the essential role of DHA in the structure and function of the brain and retina. The Improved PUFA Trial leveraged these insights and showed that the developing brain is sensitive to fatty acid intake in the context of SAM; providing DHA in RUTF improved brain development. Hepatic export of DHA into plasma and its target tissues, including the brain, relies in part on synthesis of phosphatidylcholine (PC) by phosphatidylethanolamine N-methyltransferase (PEMT). DHA-enriched PC molecules (PC-DHA) are generated by PEMT and exported for delivery throughout the body. Indeed, PEMT-deficient mice have reduced DHA plasma concentrations and pups born to PEMT-deficient dams have limited DHA brain accumulation. The PEMT pathway relies on adequate supply of dietary methyl donors such as choline. Pairing (1) choline's ability to increase DHA trafficking to/integration within the brain with (2) the power of DHA in SAM, it is possible that adding choline to RUTF containing DHA might promote cognitive recovery and development among malnourished children.
This will be an individually randomized, investigator/outcomes assessors/caregiver-blinded, controlled clinical trial designed to determine whether the addition of a daily dose of 500mg of choline to ready-to-use therapeutic food (C-RUTF) will improve cognitive development among Malawian children 6-59 months of age with SAM compared with standard RUTF (S-RUTF). This trial will be conducted at 10 rural sites in southern Malawi. 1500 children will be randomized 1:1 to receive 2 sachets per day of either C-RUTF or S-RUTF. Children will receive their allocated RUTF and return to clinic fortnightly for repeat anthropometric measurements, illness questions, and to receive more RUTF until they achieve a clinical outcome or for a maximum of 12 weeks, at which point they will undergo Malawi Developmental Assessment Tool (MDAT) testing and blood spot collection. Participants will be asked to return to clinic 5-7 months later for MDAT testing, the global z-score from which will be the trial's primary outcome.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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C-RUTF (Ready-to-Use Therapeutic Food with added choline)
A daily dose of 500mg choline will be added to RUTF. 2 sachets (daily dose) of RUTF will provide approximately 1000 Kcal, 14g of protein, 28g of fat, and 1 RDA of 14 micronutrients.
C-RUTF (Ready-to-Use Therapeutic Food with added choline)
Choline added to peanut paste-based ready-to-use therapeutic food meeting Codex Alimentarius specifications
Amoxicillin
Oral amoxicillin tablets twice per day for 7 days dosed based on weight
S-RUTF (Ready-to-Use Therapeutic Food without added choline)
A daily dose of 5mg choline will be added to RUTF for masking. 2 sachets (daily dose) of RUTF will provide approximately 1000 Kcal, 14g of protein, 28g of fat, and 1 RDA or 14 micronutrients.
S-RUTF (Ready-to-Use Therapeutic Food without added choline)
Standard peanut paste-based ready-to-use therapeutic food meeting Codex Alimentarius specifications
Amoxicillin
Oral amoxicillin tablets twice per day for 7 days dosed based on weight
Interventions
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C-RUTF (Ready-to-Use Therapeutic Food with added choline)
Choline added to peanut paste-based ready-to-use therapeutic food meeting Codex Alimentarius specifications
S-RUTF (Ready-to-Use Therapeutic Food without added choline)
Standard peanut paste-based ready-to-use therapeutic food meeting Codex Alimentarius specifications
Amoxicillin
Oral amoxicillin tablets twice per day for 7 days dosed based on weight
Eligibility Criteria
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Inclusion Criteria
* mid-upper arm circumference \< 11.5 cm and/or weight-for-length z-score \< -3 and/or presence of bilateral pedal pitting edema
* willingness to comply with all study procedures and availability for the duration of the study, including no plan to move from the catchment area of a participating clinic
Exclusion Criteria
* participation in a separate feeding program within the past month
* known allergy to study food ingredient (peanut, milk, fish)
* intention to move away from catchment area within 9 months
* developmental delay
* presence of a chronic severe medical condition (other than TB and HIV), such as congenital heart disease
6 Months
59 Months
ALL
No
Sponsors
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Project Peanut Butter
OTHER
Kamuzu University of Health Sciences
OTHER
Balchem Corporation
INDUSTRY
Washington University School of Medicine
OTHER
Responsible Party
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Principal Investigators
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Mark J Manary, MD
Role: PRINCIPAL_INVESTIGATOR
Washington University School of Medicine
Locations
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Makhwira
Makhwira, Chikwawa, Malawi
Mitondo
Mitondo, Chikwawa, Malawi
Nkhate
Nkhate, Chikwawa, Malawi
Chipolonga
Chipolonga, Machinga, Malawi
Chikonde
Chikonde, Mulanje, Malawi
Mbiza
Mbiza, Mulanje, Malawi
Milonde
Milonde, Mulanje, Malawi
Muloza
Muloza, Mulanje, Malawi
Namasalima
Namasalima, Mulanje, Malawi
Naphimba
Naphimba, Mulanje, Malawi
Countries
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Central Contacts
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Facility Contacts
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Lameck Kachali
Role: primary
Lameck Kachali
Role: primary
Lameck Kachali
Role: primary
Lameck Kachali
Role: primary
Lameck Kachali
Role: primary
Lameck Kachali
Role: primary
Lameck Kachali
Role: primary
Lameck Kachali
Role: primary
Lameck Kachali
Role: primary
Lameck Kachali
Role: primary
Other Identifiers
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202308160
Identifier Type: -
Identifier Source: org_study_id