Eggs for Gut Health

Study Overview
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Brief Summary
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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
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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.

Official Title
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Egg to Ameliorate Environmental Enteric Dysfunction and Improve Growth in Children With Moderate Acute Malnutrition

Conditions
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Moderate Acute Malnutrition, Stunting, Environmental Enteric Dysfunction, Severe Acute Malnutrition

Intervention / Treatment
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* Dietary Supplement: Whole egg powder
* Dietary Supplement: Corn powder
* Dietary Supplement: Supercereal Plus
* Dietary Supplement: Micronutrient sprinkles
* Drug: Sulfadoxine pyrimethamine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 30 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Egg powder<br>15g egg powder per day for 24 weeks | Dietary Supplement: Whole egg powder<br>* 15g daily dose for 24 weeks<br>Dietary Supplement: Supercereal Plus<br>* Approximately 110 g per day (1.5 kg every 2 weeks) supplementary food to be provided for treatment of MAM for 6 weeks.<br>Dietary Supplement: Micronutrient sprinkles<br>* To be provided after completion of MAM supplementary feeding. Provides 1 RDA of 14 micronutrients.<br>Drug: Sulfadoxine pyrimethamine<br>* 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.<br>* Other names: SP;|
| Active Comparator: Corn powder<br>15g corn powder per day for 24 weeks | Dietary Supplement: Corn powder<br>* 15g daily dose for 24 weeks<br>Dietary Supplement: Supercereal Plus<br>* Approximately 110 g per day (1.5 kg every 2 weeks) supplementary food to be provided for treatment of MAM for 6 weeks.<br>Dietary Supplement: Micronutrient sprinkles<br>* To be provided after completion of MAM supplementary feeding. Provides 1 RDA of 14 micronutrients.<br>Drug: Sulfadoxine pyrimethamine<br>* 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.<br>* Other names: SP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent lactulose excretion | % lactulose excretion in urine over >=4 hours after lactulose consumption | Collected 12 and 24 weeks after enrollment | 
| Change in length-for-age z-score | Difference in length-for-age z-score between enrollment and weeks 12 and 24. Covariate will be baseline LAZ. | Measured 12 and 24 weeks after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % Lactulose excretion >= 0.2 and >=0.45 | Proportion with moderately and severely abnormal small intestinal permeability | Collected 6, 12, and 24 weeks after enrollment | 
| Rate of length gain | mm/week | Across 24 week follow-up period | 
| LAZ < -2 | Proportion stunted | Measured 6, 12, 18, and 24 weeks after enrollment | 
| Fecal host mRNA transcripts | CD53, CDX1, HLA-DRA, TNF, S100A8, MUC12, and REG1A | Collected 12 and 24 weeks after enrollment | 
| Fecal host proteins MPO, AAT, NEO | Myeloperoxidase, alpha-1 antitrypsin, neopterin | Collected 12 and 24 weeks after enrollment | 
| Rate of weight gain | g/kg/d | Enrollment to week 6, and across 24 week follow-up period | 
| % Lactulose excretion |  | 6 weeks after enrollment | 
| Deterioration to severe acute malnutrition or death | Mid-upper arm circumference < 11.5 cm or nutritional edema | Time-to-event across follow-up period | 
| Recurrence of MAM | MUAC < 12.5 cm | Time-to-event across follow-up period | 
| Sustained recovery | Mid-upper arm circumference >= 12.5 cm without nutritional edema | Weeks 12, 18, 24 |