Study of Environmental Enteropathy and Malnutrition in Pakistan (SEEM)

Aga Khan University

Status: Completed

Conditions: Gastrointestinal Disease; Malnutrition, Child; Vaccine Response Impaired; Stunting; Enteropathy

Treatments: Other: Nutritional education; Dietary Supplement: Ready to Use Therapeutic Food; Procedure: Upper gastrointestinal endoscopy with biopsy

Study type: Interventional

Funder types: Other

Identifiers

NCT03588013

3836-Ped-ERC-15

Details and patient eligibility

About

Environmental Enteropathy (EE) is an acquired sub-clinical inflammatory gut condition in which alterations in intestinal structure, function, and local and systemic immune activation lead to impaired vaccine responses, decreased cognitive potential and undernutrition in low-middle income countries. Approximately half of all global deaths in children aged less than five years are attributable to undernutrition making the study of EE an area of critical priority. However, given the operational limitations and ethical considerations for safely obtaining intestinal biopsies from young children in low resource settings, there have been few detailed investigations of human intestinal tissue in this vulnerable patient group for whom reversal of EE would provide the greatest benefit. EE biomarkers have been studied in different settings but these have not been correlated with the gold standard histopathology confirmation. The Study of Environment Enteropathy and Malnutrition in Pakistan (SEEM Pakistan) is designed to better understand the pathophysiology, predictors, biomarkers, and potential management strategies of EE to inform strategies to eradicate this debilitating pathology.

Enrollment: 416 patients

Sex: All

Ages: Under 10 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Children aged 0-6 months from Matiari, Pakistan with weight for height Z score (WHZ) < -2 at the time of enrollment
• Children aged 0 to 6 months from Matiari, Pakistan who would be growing normally, with WHZ > 0, to serve as controls
• Healthy control children under the age of 3 years, who will undergo endoscopy at CCHMC
• Children under the age of 6 years with newly diagnosed celiac disease per endoscopy at CCHMC
• Children under the age of 10 years with newly diagnosed Crohn's disease per endoscopy at CCHMC

Exclusion criteria

• For healthy control children < 3 years old undergoing endoscopy at CCHMC, biopsies and diagnoses should not supportive of eosinophilic esophagitis
• For healthy control children < 3 years old undergoing endoscopy at CCHMC, biopsies and diagnoses should not supportive of celiac disease
• For healthy control children < 3 years old undergoing endoscopy at CCHMC, biopsies and diagnoses should not supportive of inflammatory bowel disease
• For healthy control children < 3 years old undergoing endoscopy at CCHMC, children should not have been treated with antibiotics ≤ 4 weeks prior to endoscopy

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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416 participants in 5 patient groups

Moderate/severe malnourishment

Experimental group

Description:

Pakistani children from age 0 to 6 months with weight for height Z score (WHZ) \< -2 at the time of enrollment. Parents/caregivers of all participants will undergo a series of rehabilitative interventions to improve the child's nutrition and growth. Those participants who remain WHZ \< -2 despite interventions are eligible for medical evaluation for more advanced workup of malnutrition, including UGI endoscopy and biopsy.

Treatment:

Other: Nutritional education

Dietary Supplement: Ready to Use Therapeutic Food

Procedure: Upper gastrointestinal endoscopy with biopsy

Well nourished children

Active Comparator group

Description:

Pakistani children from age 0 to 6 months who would be growing normally, with WHZ \> 0, to serve as controls. Parents/caregivers of all participants will undergo a series of rehabilitative interventions to improve the child's nutrition and growth.

Treatment:

Other: Nutritional education

US children with celiac disease

No Intervention group

Description:

Comparative group for the Pakistani WHZ \<-2 children who undergo UGI endoscopy and biopsy. Environmental Enteropathy and celiac disease have some shared features therefore we plan to enroll children under the age of 6 years with newly diagnosed celiac disease per endoscopy at CCHMC to assess the extent to which gene signatures and associated biologic pathways for children with celiac disease or environmental enteropathy overlap or differ.

US children with Crohn's disease

No Intervention group

Description:

Comparative group for the Pakistani WHZ \<-2 children who undergo UGI endoscopy and biopsy. As some differentially expressed ileal gene signatures for Crohn's disease bear remarkable similarities to individual gene expression patterns previously reported for EE, children under the age of 10 years with newly diagnosed Crohn's disease per endoscopy at CCHMC will be enrolled to study these similarities and any differences

Healthy age-matched US children

No Intervention group

Description:

Comparative group for the Pakistani WHZ \<-2 children who undergo UGI endoscopy and biopsy. Number of upper gastrointestinal endoscopies performed in children less than 2 years old are limited in Pakistan, therefore US age-matched controls will be used; healthy children \< 3 years old will be enrolled, who will undergo endoscopy at CCHMC as part of a diagnostic workup for digestive symptoms, but whose biopsies and diagnoses are not supportive of eosinophilic esophagitis, celiac disease, or inflammatory bowel disease, and who were not treated with antibiotics ≤ 4 weeks prior to endoscopy.