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Table 1 Interventional studies testing management strategies for EED, or using interventions to better understand EED

From: Environmental enteric dysfunction: a review of potential mechanisms, consequences and management strategies

Study title Study population Target sample size Intervention arm(s) Control arm(s) Primary outcome(s)
 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
 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, 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
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
  1. Abbreviations: EED Environmental enteric dysfunction, HAZ Height-for-age z-score, L:M Lactulose-to-mannitol ratio, WAZ Weight-for-age z-score, WHZ Weight-for-height z-score