Table 1 Interventional studies testing management strategies for EED, or using interventions to better understand EED
Study title | Study population | Target sample size | Intervention arm(s) | Control arm(s) | Primary outcome(s) |
|---|---|---|---|---|---|
Complete | |||||
 Lactoferrin and lysozyme supplementation for environmental enteric dysfunction | Children 12–25 months old, Malawi | 235 | Lactoferrin and lysozyme, 16 weeks | Placebo | L:M at 8 and 16 weeks |
 The impact of legumes vs corn-soy flour on environmental enteric dysfunction in rural Malawian children 1–3 year olds | Children 12–35 months old, Malawi | 337 | Cowpeas complementary food, 12 months Common bean complementary food, 12 months | Corn-soy flour | L:M at 3, 6, and 12 months |
 The impact of legumes vs corn-soy flour on environmental enteric dysfunction in rural Malawian children 6–11 months | Children 6–11 months old, Malawi | 312 | Cowpeas complementary food, 6 months Common bean complementary food, 6 months | Corn-soy flour | L:M at 3 and 6 months |
 Intervention and mechanisms of alanyl-glutamine for inflammation, nutrition, and enteropathy (IMAGINE) | Children 2 months to 5 years old, ≤ − 1 for: HAZ WAZ, or WHZ, Brazil | 112 | Alanyl-glutamine, 10 days | Glycine for 10 days | L:M on D 1, 10–13, 30–37 |
 Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction | Children 12–60 months old with mid upper arm circumference < 11.5 cm or bilateral pedal edema, Kenya | 44 | Mesalazine, 28 days | Placebo | Safety and acceptability at 28 days |
Ongoing | |||||
 Azithromycin to prevent post-discharge morbidity and mortality in Kenyan children (Toto Bora) | Children 1–59 months old discharged from hospital, Kenya | 1400 | Azithromycin, 5 days | Placebo | Death or readmission with 6 months |
 Pilot study of PTM202 for the treatment of environmental enteric dysfunction (EED) | Children 6–9 months old WAZ −1 to − 3, Bangladesh | 200 | PTM202, 30 days | Micronutrient sprinkles | EED biomarker composite score (REG1B, MPO, L:M, sCD14, CRP) at 4 months |
 Clinical effectiveness trial of PTM1001 to reduce stunting and ameliorate environmental enteric dysfunction in Malawian infants | Healthy children 10 months old, Malawi | 250 | Egg powder + bovine colostrum + multiple micronutrient sprinkle powder, 12 weeks | Corn-soya blend + multiple micronutrient sprinkle powder | Linear growth at 12 weeks |
 Protein Plus: improving infant growth through diet and enteric health (JiVitA-6) | Children 3–6 months old born to women enrolled in ongoing community trial, Bangladesh | 3180 | Azithromycin Azithromycin, protein Azithromycin, isocaloric supplement Azithromycin, daily egg provided to infants 6–12 months 3 days | Placebo Placebo, protein supplement Placebo, isocaloric supplement, Placebo, egg provided daily to infants 6–12 months old | HAZ at 12 months |
 Effects of EED on Zinc absorption and retention in children from a standard dose (ZEED1) | Children with and without EED (defined by L:M), Bangladesh | 40 | Zinc sulfate supplement, 0.5 mg of 13C10-retinyl-acetate, 1 day | – | Zinc absorption Endogenous fecal zinc Vitamin A absorption |
 Effects of EED on Zinc absorption and retention in children from a MNP (ZEED2) | Children 18–24 months old with LAZ−1.5 to −3.0 and hemoglobin ≥8, Bangladesh | 80 | Micronutrients + 15 mg zinc Micronutrients + 10 mg zinc Micronutrient + 5 mg zinc 1 day | Micronutrient without zinc | Total daily absorbed zinc |
 Early life interventions for childhood growth and development in Tanzania (ELICIT) | Children ≤14 days old, Tanzania | 1188 | Nicotinamide, azithromycin, nitazoxanide Placebo, azithromycin, nitazoxanide Nicotinamide, placebo, placebo | Azithromycin, placebo, Nitazoxanide, placebo | HAZ at 18 months |
 Safety, acceptability, and feasibility of Enterade® (SAFE) | Children 12–24 months old, HAZ − 3 to − 1, Kenya | 66 | Enterade, 14 days | Placebo | Frequency of severe adverse events Volume of daily consumption |
 Therapeutic approaches to malnutrition enteropathy (TAME) | Children 6–59 months old, hospitalized with severe acute malnutrition and clinically stable, Zambia | 235 | Colostrum GInNAC Teduglutide Budenoside 14 days | Standard of care WHO guidelines of severe acute malnutrition | EED composite score at 18 days |
 Study of environmental enteropathy and malnutrition | Children 0–6 months old, WHZ < −2, Pakistan Children 0–6 months old, WHZ > 0, Pakistan Healthy children < 3 years old, USA Children < 6 years old, newly diagnosed celiac disease, USA Children < 10 years old with newly diagnosed Crohn’s disease, USA | 500 | Ready-to-use supplementary foods (AchaMum), 60–90 days | Educational program focused on breastfeeding and complementary feeding No intervention: US children with celiac disease, Crohn’s disease, and healthy age-matched US children | Nutritional status at 3–6 months and 9 months Association biomarkers with EED at 3–6 months Association of biomarkers with EED at 9 months Association biomarkers at time of endoscopy and biopsy Upper gastrointestinal tissue biopsy and multiomic validation of EED biomarkers |
 Environmental enteropathy in Zambia: biomarkers defined by pathogenesis | Children < 18 months old, HAZ < − 2, Zambia | 400 | HEPS (corn-soya blend) + daily egg + micronutrient sprinkles | – | UGI endoscopy with validation of EED biomarkers |