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Study of Environmental Enteropathy and Malnutrition in Pakistan (SEEM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03588013
Recruitment Status : Completed
First Posted : July 17, 2018
Last Update Posted : September 8, 2021
Sponsor:
Collaborators:
University of Virginia
Children's Hospital Medical Center, Cincinnati
Bill and Melinda Gates Foundation
Washington University School of Medicine
Massachusetts General Hospital
Information provided by (Responsible Party):
Dr Syed Asad Ali, 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.

Condition or disease Intervention/treatment Phase
Malnutrition, Child Enteropathy Vaccine Response Impaired Stunting Gastrointestinal Disease Other: Nutritional education Dietary Supplement: Ready to Use Therapeutic Food Procedure: Upper gastrointestinal endoscopy with biopsy Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 416 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
  1. Moderately or severely malnourished (weight for height Z score (WHZ) < -2) children
  2. Well-nourished (WHZ > 0) children
  3. Control group of children in the US with celiac disease
  4. Control group of children in the US with Crohn's disease
  5. Control group of healthy age-matched children in the US
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Study of Environmental Enteropathy and Malnutrition in Pakistan
Actual Study Start Date : March 1, 2016
Actual Primary Completion Date : July 31, 2019
Actual Study Completion Date : July 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malnutrition

Arm Intervention/treatment
Experimental: Moderate/severe malnourishment
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.
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.
Other Name: Education

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.
Other Name: RUTF

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.
Other Names:
  • UGI endoscopy
  • Biopsy
  • Esophagoduodenoscopy

Active Comparator: Well nourished children
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.
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.
Other Name: Education

No Intervention: US children with celiac disease
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.
No Intervention: US children with Crohn's disease
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
No Intervention: Healthy age-matched US children
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.



Primary Outcome Measures :
  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



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Ages Eligible for Study:   up to 10 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03588013


Locations
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Pakistan
Aga Khan University
Karachi, Sindh, Pakistan, 74800
Sponsors and Collaborators
Aga Khan University
University of Virginia
Children's Hospital Medical Center, Cincinnati
Bill and Melinda Gates Foundation
Washington University School of Medicine
Massachusetts General Hospital
Investigators
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Principal Investigator: Syed Asad Ali, MD, MPH Aga Khan University
Principal Investigator: Sean R Moore, MD University of Virginia
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dr Syed Asad Ali, Associate Professor, Department of Pediatrics and Child Health, Aga Khan University
ClinicalTrials.gov Identifier: NCT03588013    
Other Study ID Numbers: 3836-Ped-ERC-15
First Posted: July 17, 2018    Key Record Dates
Last Update Posted: September 8, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Malnutrition
Child Nutrition Disorders
Nutrition Disorders