Clinical trial NCT04109352: Labelled Carbon Sucrose Breath Test (13C-SBT) as a Marker of Environmental Enteropathy
Official title: Validation and Field-applicability of a 13C-Sucrose Breath Test to Assess Carbohydrate Uptake and Utilization in Environmental Enteropathy Among Children in Resource Poor Settings: A Multi-site Prospective Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Glucose-Galactose Malabsorption
Enteropathy
Malnutrition, Child
Intestinal Permeability
Linear Growth Failure
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: International Atomic Energy Agency
name: Flinders University
name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: St. John's Research Institute
name: The University of The West Indies
name: Mmust Masinde Muliro University of Science and Technology
name: Asociacion Benefica Prisma
name: Scottish Universities Environmental Research Centre
name: University of Michigan
name: Tropical Diseases Research Centre, Zambia
name: Gastroenterology Services, Ltd.
First posted: 2019-09-30
Enrollment: 600
Sex: ALL
Minimum age (years): 12
Maximum age (years): 15
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Because of exigent test requirements enrollment will be restricted to convenience samples from populations near centers of excellence in nutritional studies in Dhaka, Bangladesh (the International Centre for Diarrhoeal Disease Research); Bangalore, India (St. John's Research Institute, St. John's National Academy of Health Sciences); Kingston, Jamaica (The Tropical Metabolism Research Unit of the Caribbean Institute for Health Research, University of West Indies); Kakamega, Kenya (Masinde Muliro University of Science and Technology); Iquitos, Peru44 (Asociación Benefica PRISMA and the University of Virginia); and Ndola, Zambia (Tropical Disease Research Centre). These sites represent a range of epidemiologic contexts which will enhance the cross-context applicability of study results.

Brief summary: Linear growth failure, a manifestation of chronic undernutrition in early childhood, is a recalcitrant problem in resource constrained settings. The underlying causes of growth failure are multifactorial, but persistent and recurrent infection and inflammation of the gastrointestinal tract and immune activation, a condition commonly referred to as environmental enteropathy, is an important contributor. A highly enriched 13C-Sucrose Breath Test, a measure of sucrase-isomaltase activity, will be evaluated as a non-invasive biomarker of environmental enteropathy, and more specifically of intestinal brush border enzyme activity in 6 resource poor countries (Bangladesh, India, Jamaica, Kenya, Peru and Zambia) in 100 volunteers aged 12-15 months (total n=600) and evaluated relative to the lactose rhamnose test and linear and ponderal growth over a 3-6 month period following biomarker assessment. Field usability will also be assessed.

Detailed description: Environmental enteropathy is associated with linear and ponderal growth shortfalls in young children in resource constrained settings. However, the physiological alterations of intestinal function that accompany both the demonstrable evidence of inflammation and architectural changes seen in biopsies from effected children have yet to be elucidated, and this knowledge gap limits the development of effective strategies to optimally manage the condition. Furthermore, a limited number of non-invasive assays exist with which to assess the presence of environmental enteropathy in low resource settings. This study aims 1) to determine if sucrose-isomaltase enzyme is altered in children with environmental enteropathy by using a 13C-Sucrose breath test 2) to determine if the test is able to be employed in resource limited settings.

Eligibility criteria: Inclusion Criteria:

All children will be recruited and enrolled through convenience sampling, either at the community level (if the study site has previously censused the community) or through child clinic visits.

Exclusion Criteria:

1. Severe acute malnutrition
2. HIV positive
3. Weight for height Z \>+2
4. Known medical illness contributing to growth failure

Primary outcomes:
measure: Comparison of SBT to Lactulose rhamnose (LR) test-% dose 90 min
timeFrame: 6 months after enrollment is completed
measure: Comparison of SBT to Lactulose rhamnose (LR) test- time to 50% recovery
timeFrame: 6 months after enrollment is completed
measure: Correlation of SBT (% recovery at 90 minutes) to Lactulose rhamnose (LR) test-Lactulose recovery
timeFrame: 6 months after enrollment is completed
measure: Correlation of SBT (time to 50% recovery) to Lactulose rhamnose (LR) test-Lactulose recovery
timeFrame: 6 months after enrollment is completed
measure: Correlation of SBT (% dose recovered at 09 minutes) to Lactulose rhamnose (LR) test-Mannitol recovery
timeFrame: 6 months after enrollment is completed
measure: Correlation of SBT (time to recovery of 50% of dose) to Lactulose rhamnose (LR) test-Mannitol recovery
timeFrame: 6 months after enrollment is completed
measure: Characterize the relationship between SBT (% of dose recovered at 90 min) and baseline childhood anthropometrics (attained length)
timeFrame: 6 months after enrollment is completed
measure: Characterize the relationship between SBT (time to recovery of 50% of dose) and baseline childhood anthropometrics (attained length)
timeFrame: 6 months after enrollment is completed
measure: Characterize the relationship between SBT and childhood anthropometrics (attained weight)
timeFrame: 6 months after enrollment is completed
measure: Characterize the relationship between SBT and childhood anthropometrics (attained weight for height)
timeFrame: 6 months after enrollment is completed
measure: Characterize the relationship between SBT (time to 50% recovery of 13C) and childhood linear growth, 3 months
timeFrame: 6 months after enrollment is completed
measure: Characterize the relationship between SBT and childhood linear growth, 6 months
timeFrame: 6 months after enrollment is completed
measure: Characterize the relationship between SBT (% dose recovered at 90 min)and childhood linear growth, 3 months
timeFrame: 6 months after enrollment is completed
measure: Characterize the relationship between SBT and childhood linear growth
timeFrame: 6 months after enrollment is completed
Secondary outcomes:
measure: Assess the relationship between the 13C-SBT (% recovery 90min) and fecal myeloperoxidase
timeFrame: Six months from the enrollment of the last subject
measure: Assess the relationship between SBT ( time to recovery of 50% of the 13C-tracer) and fecal myeloperoxidase
timeFrame: Six months from the enrollment of the last subject
measure: Assess the relationship between the 13C-SBT (% recovery 90 min) and serum fatty acid binding protein
timeFrame: Six months from the enrollment of the last subject
measure: Assess the relationship between the 13C-SBT (time to 50% recovery) and serum fatty acid binding protein concentration
timeFrame: Six months from the enrollment of the last subject
measure: Assess the relationship between the 13C-SBT (time to 50% recovery) and kynurenine tryptophan ratio
timeFrame: Six months from the enrollment of the last subject
measure: Assess the relationship between the 13C-SBT (% recovery at 90 minutes) and kynurenine tryptophan ratio,
timeFrame: Six months from the enrollment of the last subject
measure: Assess the relationship between the 13C-SBT as assessed by percent of 13C tracer recovered in at 90 minutes and fecal alpha-antitrypsin concentration
timeFrame: Six months from the enrollment of the last subject
measure: Assess the relationship between the 13C-SBT as measured by the time to 50% recovery of 13C and fecal alpha-antitrypsin
timeFrame: Six months from the enrollment of the last subject
Other outcomes:
measure: Reproducibility of the 13C-SBT test , percent of dose recovered in first 90 minutes
timeFrame: Six months from the enrollment of the last subject
measure: Reproducibility of the 13C-SBT test, time to 50% area under the curve of 13C tracer, expressed in minutes
timeFrame: Six months from the enrollment of the last subject
measure: Epidemiologic factors that influence 13C-SBT measure, percent of dose recovered at 90 minutes
timeFrame: Six months from the enrollment of the last subject
measure: Epidemiologic factors that influence 13C-SBT measure, time to 50% AUC recovered
timeFrame: Six months from the enrollment of the last subject
Locations:
city: Adelaide
country: Australia
facility: Flinders University
city: Dhaka
country: Bangladesh
facility: Nutrition and Clincial Services Division, icddr, b
city: Bengaluru
country: India
facility: CBCI Society for Medical Education, St John's Research Institute
city: Kingston
country: Jamaica
facility: Tropical Metabolism Research Unit, University of West Indies
city: Kakamega
country: Kenya
facility: Masinde Muliro University of Science and Technology
city: Iquitos
country: Peru
facility: Investigaciones Biomedicas, Asociacion Benefica PRISMA
city: East Kilbride
country: United Kingdom
facility: Scottish Universities Environmental Research Centre
city: Lusaka
country: Zambia
facility: Tropical Gastroenterology & Nutrition Ltd
city: Ndola
country: Zambia
facility: Tropical Diseases Research Centre
Study officials:
affiliation: International Atomic Energy Agency
name: Victor Owino, PhD
role: STUDY_CHAIR
References:
citation: Lee GO, Schillinger R, Shivakumar N, Whyte S, Huq S, Ochieng Konyole S, Chileshe J, Paredes-Olortegui M, Owino V, Yazbeck R, Kosek MN, Kelly P, Morrison D. Optimisation, validation and field applicability of a 13C-sucrose breath test to assess intestinal function in environmental enteropathy among children in resource poor settings: study protocol for a prospective study in Bangladesh, India, Kenya, Jamaica, Peru and Zambia. BMJ Open. 2020 Nov 17;10(11):e035841. doi: 10.1136/bmjopen-2019-035841.