Eggs for Gut Health

Stunting Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06002438
• Other study ID #: 202306090
• Status: Recruiting
• Phase: N/A
• Start date: October 9, 2023
• Est. completion date: October 2024

Study information

• Verified date: May 2024
• Source: Washington University School of Medicine
• Contact: Mark J Manary, MD
• Phone: +1 314-454-2341
• Email: manarymj[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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?

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 30 Months

Eligibility

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

Related Conditions & MeSH terms

• Environmental Enteric Dysfunction
• Malnutrition
• Moderate Acute Malnutrition
• Severe Acute Malnutrition
• Stunting

Intervention

Dietary Supplement:
• Whole egg powder
15g daily dose for 24 weeks
• Corn powder
15g daily dose for 24 weeks
• Supercereal 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.
• Micronutrient sprinkles
To be provided after completion of MAM supplementary feeding. Provides 1 RDA of 14 micronutrients.

Drug:
• Sulfadoxine pyrimethamine
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.

Locations

Country	Name	City	State
Sierra Leone	Bandajuma	Bandajuma	Southern
Sierra Leone	Bendu Maleh	Bendu	Southern
Sierra Leone	Blama Massaquoi	Blama Massaquoi	Southern
Sierra Leone	Gbondapi	Gbondapi	Southern
Sierra Leone	Gofor	Gofor	Southern
Sierra Leone	Jendema	Jendema	Southern
Sierra Leone	Potoru	Potoru	Southern
Sierra Leone	Pujehun Static	Pujehun	Southern
Sierra Leone	Taninahun	Taninahun	Southern
Sierra Leone	Zimmi	Zimmi	Southern

Sponsors (4)

Lead Sponsor	Collaborator
Washington University School of Medicine	Ministry of Health and Sanitation, Sierra Leone, Project Peanut Butter, Thrasher Research Fund

Country where clinical trial is conducted

Sierra Leone, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent lactulose excretion	Percent lactulose excretion in urine over >=4 hours after lactulose consumption	Collected 12 and 24 weeks after enrollment
Primary	Change in length-for-age z-score	Difference in length-for-age z-score between enrollment and weeks 12 and 24	To be compared at 12 and 24 weeks after enrollment
Secondary	Percent Lactulose excretion >= 0.2 and >=0.45	Proportion with moderately and severely abnormal small intestinal permeability. Percent lactulose excretion in urine over >=4 hours after lactulose consumption	Collected 6, 12, and 24 weeks after enrollment
Secondary	Rate of length gain	mm/week	Across 24 week follow-up period
Secondary	LAZ < -2	Proportion stunted	To be compared at 12, 18, and 24 weeks after enrollment
Secondary	Fecal host mRNA transcripts	CD53, CDX1, HLA-DRA, TNF, S100A8, MUC12, and REG1A	Collected 12 and 24 weeks after enrollment
Secondary	Fecal host protein alpha-1 antitrypsin	Level of alpha-1 antitrypsin, mg/g	Collected 12 and 24 weeks after enrollment
Secondary	Fecal host protein myeloperoxidase	Level of myeloperoxidase, ng/mL	Collected 12 and 24 weeks after enrollment
Secondary	Fecal host protein neopterin	Level of neopterin, nmol/L	Collected 12 and 24 weeks after enrollment
Secondary	Rate of weight gain	g/kg/d	Enrollment to week 6 (MAM treatment phase), and across 24 week follow-up period
Secondary	Percent Lactulose excretion	Percent lactulose excretion in urine over >=4 hours after lactulose consumption	6 weeks after enrollment
Secondary	Deterioration to severe acute malnutrition	Mid-upper arm circumference < 11.5 cm and/or nutritional edema	Time-to-event across follow-up period
Secondary	Recurrence of MAM	Development of MUAC < 12.5 cm among those who achieved MUAC >= 12.5 cm during initial MAM treatment	Time-to-event across follow-up period
Secondary	Sustained recovery	Defined by achievement mid-upper arm circumference >= 12.5 cm without nutritional edema and maintenance of MUAC >= 12.5 cm throughout follow-up thereafter.	Across 24 week follow-up period
Secondary	Death	As defined by caregiver report	Time-to-event across follow-up period
Secondary	Graduation	Defined by mid-upper arm circumference >= 12.5 cm	Within 6 weeks of enrollment