Study of Environmental Enteropathy and Malnutrition in Pakistan

Gastrointestinal Disease Clinical Trial

— SEEM  

Official title:

Study of Environmental Enteropathy and Malnutrition in Pakistan

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03588013
• Other study ID #: 3836-Ped-ERC-15
• Status: Completed
• Phase: N/A
• Start date: March 1, 2016
• Est. completion date: July 31, 2019

Study information

• Verified date: September 2021
• Source: Aga Khan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 416
• Est. completion date: July 31, 2019
• Est. primary completion date: July 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 10 Years

Eligibility

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

Related Conditions & MeSH terms

• Child Nutrition Disorders
• Digestive System Diseases
• Enteropathy
• Gastrointestinal Disease
• Gastrointestinal Diseases
• Intestinal Diseases
• Malnutrition
• Malnutrition, Child
• Stunting
• Vaccine Response Impaired

Intervention

Other:
• Nutritional education
4 week home delivered educational program that will focus on breast feeding and complimentary feeding. If child remains WHZ < -2 at by 9 months of age families will be shown 10 minute educational video detailing best practices for complimentary feeding.

Dietary Supplement:
• Ready to Use Therapeutic Food
If child remains WHZ < -2 despite nutritional education then will be managed according to Pakistan's Community Management of Acute Malnutrition protocol. This will include provision of ready to use therapeutic food (RUTF) to the child at home with close follow up. Utilization of the RUTF will be monitored closely by bi-weekly home visits.

Procedure:
• Upper gastrointestinal endoscopy with biopsy
If child remains at WHZ < -2 despite educational and dietary interventions, then will undergo medical evaluation for assessment of need for more advanced workup of malnutrition, including UGI endoscopy at AKUH. Results of the advanced work up, including the UGI endoscopy, will guide future management of these children.

Locations

Country	Name	City	State
Pakistan	Aga Khan University	Karachi	Sindh

Sponsors (6)

Lead Sponsor	Collaborator
Aga Khan University	Bill and Melinda Gates Foundation, Children's Hospital Medical Center, Cincinnati, Massachusetts General Hospital, University of Virginia, Washington University School of Medicine

Country where clinical trial is conducted

Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nutritional status in children assessed by measuring parameters of growth at 3-6 months of age	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.	Approximately 3-6 months after entry into study
Primary	Nutritional status in children assessed by measuring parameters of growth at 9 months of age	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.	At approximately 9 months after entry into study
Primary	Association of biomarkers with Environmental Enteropathy at 3-6 months of age	Serum, stool, and urine biomarkers of EE will be collected and tested in malnourished and well-nourished children	Approximately 3-6 months after entry into study
Primary	Association of biomarkers with Environmental Enteropathy at 9 months of age	Serum, stool, and urine biomarkers of EE will be collected and tested in malnourished and well-nourished children	At approximately 9 months after entry into study
Primary	Association of biomarkers with Environmental Enteropathy at the time of endoscopy and biopsy	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	At approximately 15 months after entry into study
Primary	The use of UGI biopsy tissue for histopathological and multiomic workup for validation of biomarkers associated with EE	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	At approximately 15 months after entry into study