Moderate Acute Malnutrition, Stunting, Environmental Enteric Dysfunction, Severe Acute Malnutrition
Conditions
Brief summary
The goal of this clinical trial is to test egg powder supplementation in children with moderate acute malnutrition in Sierra Leone. The main question it aims to answer is: \- Will provision of 15g of whole egg powder per day during and after treatment for moderate acute malnutrition (for 24 weeks total) improve small intestinal permeability and linear growth among 6-30 month old Sierra Leonean children compared with daily corn powder supplementation?
Detailed description
Undernutrition in children manifests as wasting, stunting, or both. While wasting is generally responsive to high-quality nutritional interventions, stunting is less so. Affected children are at increased risk of acute and chronic illnesses, have reduced neurocognitive development, lower academic achievement, reduced adult earning potential, and shortened lifespans. Given that stunting affects over 140 million children at any one time, the costs incurred are deep and broad, particularly among children in sub-Saharan Africa, where nearly half of the world's population growth is expected to occur over the next 30 years. Part of the challenge of treating stunting has been attributed to environmental enteric dysfunction (EED), an acquired small intestine disorder characterized by chronic inflammation, villus blunting, and impaired nutrient absorption. EED is prevalent in the same populations plagued by stunting, develops concurrently with loss in linear growth, and has explained upwards of 43% of observed growth faltering. EED has recently also been found in over 75% of children with moderate acute malnutrition (MAM, moderate wasting) in Sierra Leone, a population with high rates of deterioration to severe acute malnutrition and death, 20%. EED is a plausible cause for this treatment resistance, and for the high rates of recurrence seen in these children. There is an urgent need to increase understanding of the concurrence of stunting, EED, and wasting, and to test interventions targeted to their pathological underpinnings. Dietary egg can play a critical role in the fight against malnutrition by providing abundant high-quality protein and nutrients essential for physical and cognitive recovery. One egg/day has been shown to reduce stunting in several contexts. Recent evidence has shown that short-term egg/bovine colostrum supplement given to 9-12-month-old Malawian children improved linear growth and intestinal permeability in children with severe EED. It is possible that prolonged supplementation with egg in a high-risk population in rural Sierra Leone could improve acute and long-term health trajectories for children and put eggs on the map for food aid. This will be a randomized, investigator-blinded, controlled clinical trial testing whether daily supplementation with 15g whole egg powder during and for 18 weeks after treatment for moderate acute malnutrition might reduce intestinal permeability and improve linear growth, among other outcomes, when compared with control corn powder. Children with relatively higher risk MAM will be enrolled (MUAC \< 12.5 cm AND MUACz \< -2), treated with Supercereal Plus for up to 6 weeks, and undergo urine and stool collections at 6, 12, and 24 weeks. Urine collections will be for assessment of lactulose permeability and will involve participant consumption of a known amount of lactulose and collection of all urine over at least 4 hours thereafter. Stool collections will be for fecal host mRNA transcripts and selected proteins. Participants will also receive intermittent malaria chemoprophylaxis.
Interventions
DIETARY_SUPPLEMENTWhole egg powder
15g daily dose for 24 weeks
DIETARY_SUPPLEMENTCorn powder
15g daily dose for 24 weeks
DIETARY_SUPPLEMENTSupercereal Plus
Approximately 110 g per day (1.5 kg every 2 weeks) supplementary food to be provided for treatment of MAM for up to 6 weeks.
DIETARY_SUPPLEMENTMicronutrient sprinkles
To be provided after completion of MAM supplementary feeding. Provides 1 RDA of 14 micronutrients.
Infants \< 12 months of age: 250/12.5mg SP at enrollment, week 6, week 12, week 18. Infants \>= 12 months of age: 500/25mg SP at enrollment, week 6, week 12, week 18.
Sponsors
Project Peanut Butter
Thrasher Research Fund
Ministry of Health and Sanitation, Sierra Leone
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
The intervention and control powders will be packaged such that investigators and outcomes assessors will not know their identity. Participants and care providers are likely to be able to distinguish them, however.
Eligibility
Sex/Gender
ALL
Age
6 Months to 30 Months
Healthy volunteers
No
Inclusion criteria
* At least 6 months of age and less than 30 months of age * Mid-upper arm circumference \>= 11.5cm and \< 12. 5 cm * Mid-upper arm circumference-for-age z-score \< -2 * Provision of signed (or thumb-printed) and dated informed consent form * Stated 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
* Nutritional edema * Simultaneous involvement in another research trial or supplementary feeding program * Chronic debilitating illness * Allergy to egg * Receipt of treatment for acute malnutrition within 1 month prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent lactulose excretion | Collected 12 and 24 weeks after enrollment | Percent lactulose excretion in urine over \>=4 hours after lactulose consumption |
| Change in length-for-age z-score | To be compared at 12 and 24 weeks after enrollment | Difference in length-for-age z-score between enrollment and weeks 12 and 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LAZ < -2 | To be compared at 12, 18, and 24 weeks after enrollment | Proportion stunted |
| Fecal host mRNA transcripts | Collected 12 and 24 weeks after enrollment | CD53, CDX1, HLA-DRA, TNF, S100A8, MUC12, and REG1A |
| Fecal host protein alpha-1 antitrypsin | Collected 12 and 24 weeks after enrollment | Level of alpha-1 antitrypsin, mg/g |
| Fecal host protein myeloperoxidase | Collected 12 and 24 weeks after enrollment | Level of myeloperoxidase, ng/mL |
| Fecal host protein neopterin | Collected 12 and 24 weeks after enrollment | Level of neopterin, nmol/L |
| Rate of weight gain | Enrollment to week 6 (MAM treatment phase), and across 24 week follow-up period | g/kg/d |
| Percent Lactulose excretion >= 0.2 and >=0.45 | Collected 6, 12, and 24 weeks after enrollment | Proportion with moderately and severely abnormal small intestinal permeability. Percent lactulose excretion in urine over \>=4 hours after lactulose consumption |
| Deterioration to severe acute malnutrition | Time-to-event across follow-up period | Mid-upper arm circumference \< 11.5 cm and/or nutritional edema |
| Recurrence of MAM | Time-to-event across follow-up period | Development of MUAC \< 12.5 cm among those who achieved MUAC \>= 12.5 cm during initial MAM treatment |
| Sustained recovery | Across 24 week follow-up period | Defined by achievement mid-upper arm circumference \>= 12.5 cm without nutritional edema and maintenance of MUAC \>= 12.5 cm throughout follow-up thereafter. |
| Death | Time-to-event across follow-up period | As defined by caregiver report |
| Graduation | Within 6 weeks of enrollment | Defined by mid-upper arm circumference \>= 12.5 cm |
| Percent Lactulose excretion | 6 weeks after enrollment | Percent lactulose excretion in urine over \>=4 hours after lactulose consumption |
| Rate of length gain | Across 24 week follow-up period | mm/week |
Countries
Sierra Leone
Outcome results
None listed