Eggs for Gut Health

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

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?

Study Overview

• Status: Recruiting
• Conditions: Environmental Enteric Dysfunction; Moderate Acute Malnutrition; Stunting; Severe Acute Malnutrition
• Intervention / Treatment: Dietary supplement: Whole egg powder; Dietary supplement: Micronutrient sprinkles; Drug: Sulfadoxine pyrimethamine; Dietary supplement: Corn powder; Dietary supplement: Supercereal Plus

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mark J Manary, MD; Phone Number: +1 314-454-2341; Email: manarymj@wustl.edu

Study Locations

• Sierra Leone
  • Southern
    • Bandajuma, Southern, Sierra Leone
      • Recruiting
      • Bandajuma
    • Bendu, Southern, Sierra Leone
      • Recruiting
      • Bendu Maleh
    • Blama Massaquoi, Southern, Sierra Leone
      • Recruiting
      • Blama Massaquoi
    • Gbondapi, Southern, Sierra Leone
      • Recruiting
      • Gbondapi
    • Gofor, Southern, Sierra Leone
      • Recruiting
      • Gofor
    • Jendema, Southern, Sierra Leone
      • Recruiting
      • Jendema
    • Potoru, Southern, Sierra Leone
      • Recruiting
      • Potoru
    • Pujehun, Southern, Sierra Leone
      • Recruiting
      • Pujehun Static
    • Taninahun, Southern, Sierra Leone
      • Recruiting
      • Taninahun
    • Zimmi, Southern, Sierra Leone
      • Recruiting
      • Zimmi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Egg powder; 15g egg powder per day for 24 weeks	Dietary supplement: Whole egg powder; 15g daily dose for 24 weeks; Dietary supplement: 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.; Other Names: SP; Dietary supplement: Supercereal Plus; Approximately 110 g per day (1.5 kg every 2 weeks) supplementary food to be provided for treatment of MAM for 6 weeks.
Active Comparator: Corn powder; 15g corn powder per day for 24 weeks	Dietary supplement: 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.; Other Names: SP; Dietary supplement: Corn powder; 15g daily dose for 24 weeks; Dietary supplement: Supercereal Plus; Approximately 110 g per day (1.5 kg every 2 weeks) supplementary food to be provided for treatment of MAM for 6 weeks.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Thrasher Research Fund; Project Peanut Butter; Ministry of Health and Sanitation, Sierra Leone
• Investigators: Principal Investigator: Mark J Manary, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: August 10, 2023
• First Submitted That Met QC Criteria: August 15, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Severe Acute Malnutrition; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Infective Agents, Urinary; Micronutrients; Trace Elements; Pyrimethamine; Sulfadoxine; Fanasil, pyrimethamine drug combination
• Other Study ID Numbers: 202306090

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Within 12 months of primary publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No