Identification of Novel Bio-markers for Environmental Enteropathy in Children Using an Evidence Based Approach

NCT05072834 | Completed DMC

• 1 other identifier: 12-2012
• Study Type: observational
• Target: 380
• Locations: 1 country
• Sites: 1

Brief Summary

EE is increasingly recognized as a key factor underlying malnutrition, weakened immune response and impaired cognitive development in children in developing countries. Absence of a distinct biomarker of EE in the blood, urine or stool makes it difficult to study the impact of interventions against it. Biomarkers for EE have been challenging to find, partly because of our inadequate understanding of its pathophysiology. Investigators aim to identify novel biomarkers for EE, based on our hypothesis that EE is a result of two processes: 1) repeated exposure to enteric pathogens and environmental toxins leading to gut inflammation and 2) weaning on diets high in carbohydrates but low in proteins and fat, leading to atrophy of the intestinal mucosa. This leads to gut dysfunction, including leaky gut, small bowel stasis, bacterial overgrowth, decreased immune response to infections, and frequent diarrhea. The candidate biomarkers investigators have selected for our study (CRP, GLP- 2, Claudin 3, Reg-1, plasma amino acids profile, serum cytokine profile, Neopterin and Myeloperoxidase) are markers of inflammation, hormonal dysfunction and tight junction malfunction of the small intestines. The 'gold standard test' for EE will be direct histopathologic analysis of the duodenal mucosa, which will be available in a subset of study children undergoing upper GI endoscopy. For other study subjects, clinical surrogates for EE will be used to calculate the sensitivity and specificity of biomarkers being tested. These clinical surrogates of EE include HAZ and WAZ score \< 2 SD at 12 months and 15 months of age, and the worsening in HAZ and WAZ scores between 6, 9, 12 and 15 months of age. Investigators plan to study and compare duodenal biopsies from children with and without EE using cutting edge technologies including electron microscopy, immunofluorescence, and mRNA sequencing. This will allow direct correlation of the biomarkers in the blood, urine and stools with the histopathologic features of the gut mucosa. The mRNA sequencing of the gut tissue will allow us to identify new evidence-based biomarkers for EE, which could be further tested in the future. This is a strong, multidisciplinary collaboration between investigators in Pakistan and the United States with expertise in complementary areas including chemokines, inflammation, gut architecture, infectious diseases, field studies, and technology development.

Conditions

Malnutrition; Enteropathy

Keywords

Environmental Enteropathy; Childhood malnutrition; biomarkers

Outcome Measures

Primary Outcomes (2)

• Correlation of Intestinal biomarkers with growth faltering from birth to 24 months

  Investigators aimed to validate putative biomarkers of growth faltering, selected based on their role in gut inflammation \[fecal myeloperoxidase (MPO) and neopterin (NEO)\], enterocyte regeneration (Reg-1b) and proliferation \[Glucagon Like Peptide-2 (GLP2)\].

  24 months

• Correlation of systemic inflammation biomarkers with growth faltering from birth to 24 months

  We also measured the association of a few systemic inflammatory biomarkers \[serum Ferritin, c-reactive protein (CRP), α1 acid glycoprotein (AGP)\] as well as Insulin-Like Growth factor 1 (IGF-1) with linear growth

  24 months

Study Arms (2)

Cohort A

children with chronic malnutrition who do not respond to adequate supplemental feeding will undergo Upper Gastrointestinal Endoscopy

Procedure: Upper Gastrointestinal Endoscopy

Cohort B

Children 6 months to 24 months old who are undergoing Upper Gastrointestinal endoscopy for any appropriate indication

Procedure: Upper Gastrointestinal Endoscopy

Interventions

Upper Gastrointestinal Endoscopy PROCEDURE

Procedure Upper gastro-intestinal endoscopic procedure involves collection of intestinal samples and it can be helpful in identifying the causes of malnutrition. Upon parental approval, the child along with two relatives will be provided transportation to Karachi, accommodation and the compensation for their time and expenses. For this procedure the child will be admitted to the hospital a day before the procedure till one day after the procedure. This procedure takes 30 minutes, requires general anesthesia and involves insertion of a flexible tube with a small TV camera and a light on one end and an eyepiece on the other. The endoscope will allow the doctor to examine the inside of certain tube-like structures in the body. Some tissue samples for laboratory testing will be taken.

Also known as: UGI endoscopy

Cohort A; Cohort B

Eligibility Criteria

• Age: 6 Months - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

children 6- 24 months

You may qualify if:

• chronically malnourished children at 9 months of age via HAZ score and
• no adequate response despite one month of supplemental feeding, and
• if there is history of GI illness like chronic or recurrent diarrhea

You may not qualify if:

• no parental consent
• no anesthesia clearance

Sponsors & Collaborators

• Aga Khan University: lead
• University of Reading: collaborator
• Boston University: collaborator
• Washington University School of Medicine: collaborator
• University of Chicago: collaborator
• University of Virginia: collaborator

Study Sites (1)

Matiari

Matiari, Sindh, Pakistan

Location

Biospecimen

Retention: SAMPLES WITH DNA

collect blood, urine and stools at 6 and 9 months of age and test for biomarkers including GLP-2, Claudin 3, CRP, Reg 1, serum cytokines profile, plasma amino acids profile, Neopterin and Myeloperoxidase

MeSH Terms

Conditions

Malnutrition; Intestinal Diseases

Interventions

Endoscopy, Digestive System

Condition Hierarchy (Ancestors)

Nutrition Disorders; Nutritional and Metabolic Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Syed Asad Ali

  Aga Khan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 26, 2015
• First Posted: October 11, 2021
• Study Start: January 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: September 1, 2015
• Last Updated: October 11, 2021

Record last verified: 2021-10

Locations

PA (1)