Study of Environmental Enteropathy and Malnutrition in Pakistan

Not Applicable

Completed

• Conditions: Stunting; Gastrointestinal Disease; Vaccine Response Impaired; Malnutrition, Child; Enteropathy
• Interventions: Other: Nutritional education; Dietary Supplement: Ready to Use Therapeutic Food; Procedure: Upper gastrointestinal endoscopy with biopsy

• Registration Number: NCT03588013
• Lead Sponsor: Aga Khan University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-03-01
• Study First Submitted: 2018-06-19
• Study First Submitted QC: 2018-07-03
• Study First Posted: 2018-07-17
• Primary Completion: 2019-07-31
• Study Completion: 2019-07-31
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-06
• Last Update Posted: 2021-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 416

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Moderate/severe malnourishment	Nutritional education	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.
Moderate/severe malnourishment	Upper gastrointestinal endoscopy with biopsy	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.
Moderate/severe malnourishment	Ready to Use Therapeutic Food	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.
Well nourished children	Nutritional education	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.

Primary Outcome Measures

Name	Time	Method
Nutritional status in children assessed by measuring parameters of growth at 9 months of age	At approximately 9 months after entry into study	Our birth cohort will be assessed for nutritional status by measuring parameters of growth, length, weight and height. These measurements will be calculated as Z scores according to WHO tables and children will be divided into the appropriate categories: Stunting as Length for Age Z-score \< -2 SD (standard deviation), underweight as Weight-for-Age Z-score \< -2 SD and wasting as Weight-for-Length Z-score \< -2 SD, or normal-for-age.
Nutritional status in children assessed by measuring parameters of growth at 3-6 months of age	Approximately 3-6 months after entry into study	Our birth cohort will be assessed for nutritional status by measuring parameters of growth, length, weight and height. These measurements will be calculated as Z scores according to WHO tables and children will be divided into the appropriate categories: Stunting as Length for Age Z-score \< -2 SD (standard deviation), underweight as Weight-for-Age Z-score \< -2 SD and wasting as Weight-for-Length Z-score \< -2 SD, or normal-for-age.
Association of biomarkers with Environmental Enteropathy at 3-6 months of age	Approximately 3-6 months after entry into study	Serum, stool, and urine biomarkers of EE will be collected and tested in malnourished and well-nourished children
Association of biomarkers with Environmental Enteropathy at the time of endoscopy and biopsy	At approximately 15 months after entry into study	Serum, stool, and urine biomarkers of EE will be collected and tested in those children who are eligible to undergo upper GI endoscopy and biopsy
The use of UGI biopsy tissue for histopathological and multiomic workup for validation of biomarkers associated with EE	At approximately 15 months after entry into study	Biopsy specimens from UGI endoscopy obtained from eligible children will be used for detailed histopathologic and multiomic work up to study the pathophysiology of EE, validate current biomarkers, and generate novel biomarker candidates
Association of biomarkers with Environmental Enteropathy at 9 months of age	At approximately 9 months after entry into study	Serum, stool, and urine biomarkers of EE will be collected and tested in malnourished and well-nourished children

Trial Locations

Locations (1)

Aga Khan University; 🇵🇰 Karachi, Sindh, Pakistan