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NCT Number: NCT03588013

Study of Environmental Enteropathy and Malnutrition in Pakistan

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.

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Key information

Conditions

Malnutrition, Child Child Nutrition Disorders Digestive System Diseases Enteropathy Gastrointestinal Disease Gastrointestinal Diseases Growth Disorders Intestinal Diseases Nutrition Disorders Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Stunting Vaccine Response Impaired

Age range

0 day–10 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Aga Khan University

Karachi, Sindh, 74800, Pakistan

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Nutritional education

Other

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.

Other names: Education

Ready to Use Therapeutic Food

Dietary Supplement

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.

Other names: RUTF

Upper gastrointestinal endoscopy with biopsy

Procedure

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.

Other names: UGI endoscopy, Biopsy, Esophagoduodenoscopy

Primary outcomes

  1. Nutritional status in children assessed by measuring parameters of growth at 3-6 months of age

    Time frame: 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.

  2. Nutritional status in children assessed by measuring parameters of growth at 9 months of age

    Time frame: 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.

  3. Association of biomarkers with Environmental Enteropathy at 3-6 months of age

    Time frame: 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

  4. Association of biomarkers with Environmental Enteropathy at 9 months of age

    Time frame: 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

  5. Association of biomarkers with Environmental Enteropathy at the time of endoscopy and biopsy

    Time frame: 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

  6. The use of UGI biopsy tissue for histopathological and multiomic workup for validation of biomarkers associated with EE

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Aga Khan University

Other

Collaborators

  • Bill and Melinda Gates Foundation
  • Children's Hospital Medical Center, Cincinnati
  • Massachusetts General Hospital
  • University of Virginia
  • Washington University School of Medicine

Registry information

Acronym: SEEM

Important dates

Study start
2016
Primary completion
2019
Study completion
2019
First posted
Jul 17, 2018
Registry last updated
Sep 8, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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