Study of Environmental Enteropathy and Malnutrition in Pakistan
SEEM
1 other identifier
interventional
416
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Mar 2016
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2016
CompletedFirst Submitted
Initial submission to the registry
June 19, 2018
CompletedFirst Posted
Study publicly available on registry
July 17, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
July 31, 2019
CompletedSeptember 8, 2021
September 1, 2021
3.4 years
June 19, 2018
September 6, 2021
Conditions
Outcome Measures
Primary Outcomes (6)
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
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
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
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
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
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
Study Arms (5)
Moderate/severe malnourishment
EXPERIMENTALPakistani 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
ACTIVE COMPARATORPakistani 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.
US children with celiac disease
NO INTERVENTIONComparative 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 INTERVENTIONComparative 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 INTERVENTIONComparative 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.
Interventions
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Aga Khan Universitylead
- University of Virginiacollaborator
- Children's Hospital Medical Center, Cincinnaticollaborator
- Bill and Melinda Gates Foundationcollaborator
- Washington University School of Medicinecollaborator
- Massachusetts General Hospitalcollaborator
Study Sites (1)
Aga Khan University
Karachi, Sindh, 74800, Pakistan
Related Publications (4)
Ahmed S, Iqbal J, Sadiq K, Umrani F, Rizvi A, Kabir F, Jamil Z, Syed S, Ehsan L, Zulqarnain F, Sajid M, Hotwani A, Rahman N, Ma JZ, McNeal M, Ann Costa Clemens S, Talat Iqbal N, Moore SR, Ali A. Association of Anti-Rotavirus IgA Seroconversion with Growth, Environmental Enteric Dysfunction and Enteropathogens in Rural Pakistani Infants. Vaccine. 2022 May 31;40(25):3444-3451. doi: 10.1016/j.vaccine.2022.04.032. Epub 2022 May 6.
PMID: 35534310DERIVEDZhao X, Setchell KDR, Huang R, Mallawaarachchi I, Ehsan L, Dobrzykowski Iii E, Zhao J, Syed S, Ma JZ, Iqbal NT, Iqbal J, Sadiq K, Ahmed S, Haberman Y, Denson LA, Ali SA, Moore SR. Bile Acid Profiling Reveals Distinct Signatures in Undernourished Children with Environmental Enteric Dysfunction. J Nutr. 2021 Dec 3;151(12):3689-3700. doi: 10.1093/jn/nxab321.
PMID: 34718665DERIVEDHaberman Y, Iqbal NT, Ghandikota S, Mallawaarachchi I, Tzipi Braun, Dexheimer PJ, Rahman N, Hadar R, Sadiq K, Ahmad Z, Idress R, Iqbal J, Ahmed S, Hotwani A, Umrani F, Ehsan L, Medlock G, Syed S, Moskaluk C, Ma JZ, Jegga AG, Moore SR, Ali SA, Denson LA. Mucosal Genomics Implicate Lymphocyte Activation and Lipid Metabolism in Refractory Environmental Enteric Dysfunction. Gastroenterology. 2021 May;160(6):2055-2071.e0. doi: 10.1053/j.gastro.2021.01.221. Epub 2021 Jan 29.
PMID: 33524399DERIVEDIqbal NT, Syed S, Sadiq K, Khan MN, Iqbal J, Ma JZ, Umrani F, Ahmed S, Maier EA, Denson LA, Haberman Y, McNeal MM, Setchell KDR, Zhao X, Qureshi S, Shen L, Moskaluk CA, Liu TC, Yilmaz O, Brown DE, Barratt MJ, Kung VL, Gordon JI, Moore SR, Ali SA. Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation. BMC Pediatr. 2019 Jul 22;19(1):247. doi: 10.1186/s12887-019-1564-x.
PMID: 31331393DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Syed Asad Ali, MD, MPH
Aga Khan University
- PRINCIPAL INVESTIGATOR
Sean R Moore, MD
University of Virginia
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor, Department of Pediatrics and Child Health
Study Record Dates
First Submitted
June 19, 2018
First Posted
July 17, 2018
Study Start
March 1, 2016
Primary Completion
July 31, 2019
Study Completion
July 31, 2019
Last Updated
September 8, 2021
Record last verified: 2021-09