An interventional study of MFGM-RUTF (milk fat globule membrane ready-to-use therapeutic food) and S-RUTF (standard ready-to-use therapeutic food) in Severe Acute Malnutrition, Cognitive Impairment and Kwashiorkor, sponsored by Washington University School of Medicine. Active, not recruiting at 10 sites in Sierra Leone. Open to participants aged 6 Months to 59 Months. Per ClinicalTrials.gov, last updated 2026-11-03.
Sponsored by Washington University School of Medicine · Not applicable, Interventional, and Treatment
The goal of this clinical trial is to test the use of milk fat globule membrane (MFGM) in ready-to-use therapeutic food (RUTF) in children with severe acute malnutrition in Sierra Leone. The main questions it aims to answer are:
Researchers will compare the MFGM-containing RUTF to standard RUTF, which contains skim milk powder.
Participants will:
Globally, approximately 15 million children are suffering from severe acute malnutrition (SAM) at any one time, a number that has not declined in recent decades despite significant technological advancements in agriculture and food science. SAM is a condition of total-body depletion of the nutrients required for health and development; without treatment, 50% of affected children will die. Whereas historically children with SAM were admitted to and treated within hospitals, the advent of ready-to-use therapeutic food (RUTF) and community-based management of acute malnutrition revolutionized SAM care by allowing it to occur safely and successfully by the child's caregiver in their own home.
RUTF was designed to provide the nutrients required for physical recovery in a safe, palatable format. It is equal parts peanut paste, sugar, vegetable oil, and skim milk powder, with added micronutrients and emulsifier. At inception, attention was not specifically paid to how RUTF's composition might impact neurodevelopmental recovery in children with SAM. Research over the past decade has revealed that even following successful treatment with RUTF, children diagnosed with SAM still score 1-3 standard deviations below age-based expectations on neurodevelopmental tests. This suggests that the nutrient profile of standard RUTF is not sufficient to recover the developmental damage incurred by SAM.
Recently, progress has been made toward improving the developmental trajectory of children with SAM by altering RUTF. A randomized, blinded trial in Malawi including 2,500 children with SAM showed that improving the polyunsaturated fatty acid (PUFA) profile of RUTF by reducing linoleic acid and adding docosahexaenoic acid (DHA) yields superior neurodevelopment 6 months after treatment, by 0.19 standard deviations on a standardized, culturally adapted neurodevelopmental test. This demonstrates that neurodevelopmental recovery in SAM is sensitive to the lipid profile of RUTF. Despite the benefits of improved PUFA RUTF, however, children with SAM remained 1 standard deviation below expectations in neurodevelopment.
The milk fat globule membrane (MFGM) in mammalian milk contains a host of nutrients and bioactive compounds supportive of physical health and brain development. Bovine MFGM added to infant formula has been tested in several clinical trials and has demonstrated a reduction in infectious episodes, such as diarrhea and ear infections, as well as improvement in cognitive development, compared with infant formula not containing MFGM. In these trials and others, MFGM has been shown to be safe and well-tolerated. Currently, RUTF contains skim milk powder as its high-quality protein source, and peanut and vegetable oils as the primary sources of fat. These vegetable fat sources are deficient in the lipids provided by MFGM: sphingolipids, cholesterol, and other phospholipids such as phosphatidylcholine and phosphatidylethanolamine, all of which play roles in brain development. It is possible that the lipids contained in MFGM may further support neurodevelopmental recovery in SAM children.
By acting as a natural emulsifier, MFGM also offers a food formulation advantage that is relevant to children with SAM. Animal model studies have demonstrated that emulsifiers can compromise the gut barrier. Children with SAM have damaged small intestinal barrier function, which can lead to translocation of gut bacteria and resulting systemic infection. As RUTF will compose nearly 100% of a child's intake for the duration of treatment - up to 3 months - it is possible that inclusion of emulsifier may impede gut healing and recovery. Considering this concern, the Manary lab ran a clinical trial in 2018-2019 testing a novel formulation of RUTF designed with oat in place of some skim milk powder and peanut, and without hydrogenated vegetable oil (standard emulsifier), because oat acts as a natural emulsifier. In this trial, children with SAM receiving the oat-RUTF had 10% absolute higher recovery and a 33% relative reduction in the worst SAM outcomes (death, hospitalization, or remaining severely malnourished). Like oat, MFGM in RUTF allows for omission of emulsifier and may yield similar benefits.
Given (1) the repeated finding that adding MFGM to infant formulas improves neurodevelopment, (2) the impaired neurodevelopment of children with SAM, (3) the current RUTF formulation lacking neuro-supportive fats provided by MFGM, (4) MFGM's natural activity as an emulsifier, and (5), the reality that RUTF provides the sole source of nutrition for children with SAM, it is plausible that adding this high-quality source of lipids and protein to RUTF may also benefit children with SAM in both immediate and long-term physical and cognitive recovery.
This will be an individually randomized, investigator/outcomes assessors-blinded, controlled clinical trial designed to determine if treatment of severely malnourished Sierra Leonean children 6-59-months of age with an RUTF made with MFGM-containing whey protein/fat concentrate will (1) improve neurodevelopment and (2) reduce a composite of poor SAM outcomes (death, hospitalization, remaining severely malnourished), compared with standard RUTF (S-RUTF). This trial will be conducted at 20 rural sites in Sierra Leone. 1600 children will be randomized 1:1 to receive 2 sachets per day of either MFGM-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. Participants will be asked to return to clinic 6 (5-7) months later for MDAT testing, the global z-score from which will be the trial's co-primary outcome. A subset of participants will undergo blood spot and/or stool sample collection at the end of SAM treatment.
45 studies on the registry are indexed under Kwashiorkor; 5 are open to participants now.
This study's planned enrollment of 1,600 is above the median of 100 across 33 interventional studies indexed under Kwashiorkor.
Browse Kwashiorkor studies →Washington University School of Medicine is the lead sponsor of 1,803 studies on the registry; 271 are open to participants now.
Of its 329 completed or terminated interventional studies of FDA-regulated products, 216 (66%) have results posted.
Compared within Kwashiorkor, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Severe Acute Malnutrition. The counts are of registry records indexed under each term, refreshed daily. How we classify →
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Exclusion Criteria:
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The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
One sachet contains 92g of MFGM-RUTF. During SAM treatment, each participant will be given sufficient MFGM-RUTF to consume 2 sachets per day, which will provide approximately 1000 calories, 27g of protein, 63g of fat, and over 1 RDA of micronutrients.
Dietary Supplement: MFGM-RUTF (milk fat globule membrane ready-to-use therapeutic food) · Drug: Amoxicillin · Drug: Sulfadoxine (250 mg)/Pyrimethamine (12.5 mg)
One sachet contains 92g of S-RUTF. During SAM treatment, each participant will be given sufficient S-RUTF to consume 2 sachets per day, which will provide approximately 1000 calories, 27g of protein, 60g of fat, and over 1 RDA of micronutrients.
Dietary Supplement: S-RUTF (standard ready-to-use therapeutic food) · Drug: Amoxicillin · Drug: Sulfadoxine (250 mg)/Pyrimethamine (12.5 mg)
MFGM whey protein/fat concentrate powder used in place of skim milk powder in peanut paste-based ready-to-use therapeutic food meeting Codex Alimentarius specifications. There will be 10g of MFGM-containing whey protein/fat concentrate powder per 100g of MFGM-RUTF. Other ingredients and amounts per 100g: 9.5g rice flour, 5g whey permeate, 18.5g palm oil, 31g peanut paste, 22.1g sugar, 2.9g micronutrient mix, 1g fish oil.
Standard peanut paste-based ready-to-use therapeutic food made with skim milk powder meeting Codex Alimentarius specifications. This RUTF is modeled on the most widely used recipe worldwide, containing per 100g: 19.5g skim milk powder, 9.3g palm oil, 7g canola oil, 31.3g peanut paste, 28g sugar, 1g soy flakes, 1g hydrogenated vegetable oil, and 2.9g micronutrient mix.
Oral amoxicillin tablets twice per day for 7 days dosed based on weight
Drug pages: Sulfadoxine · Pyrimethamine
Malaria chemoprophylaxis, dosed by weight, to be given every month during SAM treatment
Malawi Developmental Assessment Tool global z-score
Age-standardized score, -6 to +6, higher scores are better
Time frame: 6 (5-7) months after SAM treatment completion
Composite of poor severe acute malnutrition treatment outcomes
This composite outcome will include death, hospitalization, and remaining severely malnourished despite 12 weeks of treatment
Time frame: 2-12 weeks of therapeutic feeding
Malawi Developmental Assessment Tool gross motor domain z-score
Age-standardized score, -6 to +6, higher scores are better
Time frame: 6 (5-7) months after SAM treatment completion
Malawi Developmental Assessment Tool fine motor domain z-score
Age-standardized score, -6 to +6, higher scores are better
Time frame: 6 (5-7) months after SAM treatment completion
Malawi Developmental Assessment Tool language domain z-score
Age-standardized score, -6 to +6, higher scores are better
Time frame: 6 (5-7) months after SAM treatment completion
Malawi Developmental Assessment Tool social-emotional domain z-score
Age-standardized score, -6 to +6, higher scores are better
Time frame: 6 (5-7) months after SAM treatment completion
Remaining severely malnourished at end of SAM treatment
For MUAC enrollment: MUAC \< 11.5 cm For WLZ enrollment: WLZ \< -3 For enrollment by both MUAC and WLZ: either remaining in SAM range For nutritional edema enrollment: continued edema
Time frame: 12 weeks of therapeutic feeding
Death during SAM treatment
As per caregiver/family report
Time frame: 2-12 weeks of therapeutic feeding
Hospitalization during SAM treatment
Participant determined to require hospitalization. Determination may be made by caregiver/family, government health workers, or may be recommended by trial staff for clinical decompensation.
Time frame: 2-12 weeks of therapeutic feeding
Graduation from SAM treatment
For MUAC enrollment: MUAC ≥ 12.5cm For WLZ enrollment: WLZ \> -2 based on enrollment length For MUAC and WLZ enrollment: may meet either For edema enrollment: resolution of edema, with at least 4 weeks treatment
Time frame: 2-12 weeks of therapeutic feeding
Malawi Developmental Assessment Tool global z-score
Age-standardized score, -6 to +6, higher scores are better
Time frame: Within 1 month of SAM treatment completion
Malawi Developmental Assessment Tool gross motor domain z-score
Age-standardized score, -6 to +6, higher scores are better
Time frame: Within 1 month of SAM treatment completion
Malawi Developmental Assessment Tool fine motor domain z-score
Age-standardized score, -6 to +6, higher scores are better
Time frame: Within 1 month of SAM treatment completion
Malawi Developmental Assessment Tool language domain z-score
Age-standardized score, -6 to +6, higher scores are better
Time frame: Within 1 month of SAM treatment completion
Malawi Developmental Assessment Tool social-emotional domain z-score
Age-standardized score, -6 to +6, higher scores are better
Time frame: Within 1 month of SAM treatment completion
Rate of weight change
g / kg / day
Time frame: Across initial 4 weeks of therapeutic feeding, or 2 weeks if graduate after 2 weeks
Rate of length change
mm / week
Time frame: Across 2-12 weeks of therapeutic feeding
Rate of mid-upper arm circumference change
mm / week
Time frame: Across 2-12 weeks of therapeutic feeding
Rate of change in length-for-age z-score across entire follow-up
Difference in LAZ at final visit and initial visit divided by time months transpired
Time frame: 7-10 months (2-12 weeks of therapeutic feeding, 5-7 months of follow-up thereafter)
Diarrhea incidence during SAM treatment
Caregiver report of participant diarrhea (\>2 loose stools per day) during SAM treatment
Time frame: 2-12 weeks of therapeutic feeding
Fever incidence during SAM treatment
Caregiver report of participant fever during SAM treatment
Time frame: 2-12 weeks of therapeutic feeding
Plasma DHA status at end of SAM treatment
Blood spot DHA % total fatty acids in subset of participants at end of therapeutic feeding
Time frame: Collected after 2-12 weeks of therapeutic feeding
Fecal host mRNA transcripts as markers of environmental enteric dysfunction at end of SAM treatment
CD53, CDX1, HLA-DRA, TNF, S100A8, MUC12, and REG1A
Time frame: Collected after 2-12 weeks of therapeutic feeding
Malawi Developmental Assessment Tool global z-score trajectory
Change in MDAT global z-score between initial test and final test
Time frame: 6 (5-7) months after SAM treatment completion
Malawi Developmental Assessment Tool global z-score in sub-groups
Age-standardized score, -6 to +6, higher scores are better. Will be tested in subgroups based on SAM treatment outcome (graduation vs. other), age at enrollment, and sex
Time frame: 6 (5-7) months after SAM outcome
Malawi Developmental Assessment Tool global z-score in sub-groups
Age-standardized score, -6 to +6, higher scores are better. Will be tested in subgroups based on SAM treatment outcome (graduation vs. other), age at enrollment, and sex
Time frame: Within 1 month of SAM treatment completion
Composite of poor severe acute malnutrition treatment outcomes
This composite outcome will include death, hospitalization, and remaining severely malnourished despite 12 weeks of treatment. This will be tested in subgroups by age at enrollment, sex, and enrollment criteria.
Time frame: 2-12 weeks of therapeutic feeding
Plan to share: Yes
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: Within 12 months of primary publication
No publications or documents are linked to this record.
Started Sep 2025 (actual). Primary completion is estimated for Dec 2027, 26 months after the start.
Of 21 interventional studies with no phase under Kwashiorkor, half reached primary completion within 20 months of starting (the median), counting those still running; a quarter within 10 and three quarters within 24. This study's planned 26 months is above that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is active, not recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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