Labelled Carbon Sucrose Breath Test (13C-SBT) as a Marker of Environmental Enteropathy

NCT04109352 | Unknown

• 1 other identifier: CE0783.19
• Study Type: observational
• Target: 600
• Locations: 8 countries
• Sites: 9

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.

Conditions

Glucose-Galactose Malabsorption; Enteropathy; Malnutrition, Child; Intestinal Permeability; Linear Growth Failure

Outcome Measures

Primary Outcomes (14)

• Comparison of SBT to Lactulose rhamnose (LR) test-% dose 90 min

  The 13C-SBT (cumulative percent of dose recovered at 90 minutes post administration) will be compared to LR ratio (the ratio of the percent recovery of administered lactulose and mannitol)

  6 months after enrollment is completed

• Comparison of SBT to Lactulose rhamnose (LR) test- time to 50% recovery

  The 13C-SBT (time to 50% area under the curve of 13C tracer, expressed in minutes ) will be compared to LR ratio (the ratio of the percent recovery of administered lactulose and mannitol)

  6 months after enrollment is completed

• Correlation of SBT (% recovery at 90 minutes) to Lactulose rhamnose (LR) test-Lactulose recovery

  The 13C-SBT (cumulative percent of dose recovered at 90 minutes post administration) will be compared to the percent lactulose recovery at 90 minutes post administration

  6 months after enrollment is completed

• Correlation of SBT (time to 50% recovery) to Lactulose rhamnose (LR) test-Lactulose recovery

  The 13C-SBT (time to 50% area under the curve 13C tracer, expressed in minutes) will be compared to the percent lactulose recovery at 90 minutes post administration

  6 months after enrollment is completed

• Correlation of SBT (% dose recovered at 09 minutes) to Lactulose rhamnose (LR) test-Mannitol recovery

  The 13C-SBT (cumulative percent of dose of 13C recovered at 90 minutes post administration) will be compared to percent mannitol recovery

  6 months after enrollment is completed

• Correlation of SBT (time to recovery of 50% of dose) to Lactulose rhamnose (LR) test-Mannitol recovery

  The 13C-SBT (time to 50% area under the curve 13C tracer, expressed in minutes) will be compared to percent mannitol recovery

  6 months after enrollment is completed

• Characterize the relationship between SBT (% of dose recovered at 90 min) and baseline childhood anthropometrics (attained length)

  We will compare results of the SBT test expressed as cumulative percent of dose recovered at 90 minutes post administration and LAZ (length for age Z-score as defined by 2006 World Health Organization norms, cross-sectional)

  6 months after enrollment is completed

• Characterize the relationship between SBT (time to recovery of 50% of dose) and baseline childhood anthropometrics (attained length)

  We will compare results of the SBT test expressed as time to 50% area under the curve 13C tracer, expressed in minutes and LAZ (length for age Z-score as defined by 2006 World Health Organization norms, cross-sectional)

  6 months after enrollment is completed

• Characterize the relationship between SBT and childhood anthropometrics (attained weight)

  We will compare results of the SBT test expressed as the cumulative percent of dose recovered at 90 minutes post administration and WAZ (weight for age Z-score as defined by 2006 World Health Organization norms, cross-sectional)

  6 months after enrollment is completed

• Characterize the relationship between SBT and childhood anthropometrics (attained weight for height)

  We will compare results of the SBT test expressed as time to 50% area under the curve 13C tracer, expressed in minutes and WAZ (weight for age Z-score as defined by 2006 World Health Organization norms, cross-sectional)

  6 months after enrollment is completed

• Characterize the relationship between SBT (time to 50% recovery of 13C) and childhood linear growth, 3 months

  We will compare values for the 13C-SBT expressed as time to 50% area under the curve 13C tracer, expressed in minutes and change in length for age Z score (WHO 2006 reference standards) over the subsequent 3 months

  6 months after enrollment is completed

• Characterize the relationship between SBT and childhood linear growth, 6 months

  We will compare values for the 13C-SBT expressed as time to 50% area under the curve 13C tracer, expressed in minutes and change in length for age Z score (WHO 2006 reference standards) over the subsequent 6 months

  6 months after enrollment is completed

• Characterize the relationship between SBT (% dose recovered at 90 min)and childhood linear growth, 3 months

  We will compare the 13C-SBT tests results (cumulative percent of dose recovered at 90 minutes post administration) and change in LAZ over the subsequent 3 months

  6 months after enrollment is completed

• Characterize the relationship between SBT and childhood linear growth

  We will compare the 13C-SBT tests results (cumulative percent of dose recovered at 90 minutes post administration) and change in LAZ over the subsequent 6 months

  6 months after enrollment is completed

Secondary Outcomes (8)

• Assess the relationship between the 13C-SBT (% recovery 90min) and fecal myeloperoxidase

  Six months from the enrollment of the last subject

• Assess the relationship between SBT ( time to recovery of 50% of the 13C-tracer) and fecal myeloperoxidase

  Six months from the enrollment of the last subject

• Assess the relationship between the 13C-SBT (% recovery 90 min) and serum fatty acid binding protein

  Six months from the enrollment of the last subject

• Assess the relationship between the 13C-SBT (time to 50% recovery) and serum fatty acid binding protein concentration

  Six months from the enrollment of the last subject

• Assess the relationship between the 13C-SBT (time to 50% recovery) and kynurenine tryptophan ratio

  Six months from the enrollment of the last subject

Other Outcomes (4)

• Reproducibility of the 13C-SBT test , percent of dose recovered in first 90 minutes

  Six months from the enrollment of the last subject

• Reproducibility of the 13C-SBT test, time to 50% area under the curve of 13C tracer, expressed in minutes

  Six months from the enrollment of the last subject

• Epidemiologic factors that influence 13C-SBT measure, percent of dose recovered at 90 minutes

  Six months from the enrollment of the last subject

Eligibility Criteria

• Age: 12 Months - 15 Months
• Sex: all
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of Virginia: lead
• International Atomic Energy Agency: collaborator
• Flinders University: collaborator
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• St. John's Research Institute: collaborator
• The University of The West Indies: collaborator
• Mmust Masinde Muliro University of Science and Technology: collaborator
• Asociacion Benefica Prisma: collaborator
• Scottish Universities Environmental Research Centre: collaborator
• University of Michigan: collaborator
• Tropical Diseases Research Centre, Zambia: collaborator
• Gastroenterology Services, Ltd.: collaborator

Study Sites (9)

Flinders University

Adelaide, Australia

RECRUITING

Nutrition and Clincial Services Division, icddr, b

Dhaka, Bangladesh

RECRUITING

CBCI Society for Medical Education, St John's Research Institute

Bengaluru, India

RECRUITING

Tropical Metabolism Research Unit, University of West Indies

Kingston, Jamaica

NOT YET RECRUITING

Masinde Muliro University of Science and Technology

Kakamega, Kenya

RECRUITING

Investigaciones Biomedicas, Asociacion Benefica PRISMA

Iquitos, Peru

COMPLETED

Scottish Universities Environmental Research Centre

East Kilbride, United Kingdom

RECRUITING

Tropical Gastroenterology & Nutrition Ltd

Lusaka, Zambia

NOT YET RECRUITING

Tropical Diseases Research Centre

Ndola, Zambia

NOT YET RECRUITING

Related Publications (2)

• Shivakumar N, Huq S, Paredes-Olortegui M, Konyole SO, Devi S, Yazbeck R, Owino VO, Brouwer AF, Kosek MN, Kelly P, Morrison DJ, Lee GO. A cross-sectional study of associations between the 13C-sucrose breath test, the lactulose rhamnose assay, and growth in children at high risk of environmental enteropathy. Am J Clin Nutr. 2024 Dec;120(6):1354-1363. doi: 10.1016/j.ajcnut.2024.10.001. Epub 2024 Oct 9.

  PMID: 39384142 DERIVED

• 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.

  PMID: 33203623 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Breath prior to and following enriched sucrose ingestion, plasma, saliva, stool, urine following the ingestion of rhamnose and lactulose

MeSH Terms

Conditions

Glucose-Galactose Malabsorption; Intestinal Diseases; Child Nutrition Disorders; Failure to Thrive

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Victor Owino, PhD

  International Atomic Energy Agency

  STUDY CHAIR

Central Study Contacts

Margaret N Kosek, MD

CONTACT

434-243-9552; mkosek@virginia.edu

Victor Owino, PhD

CONTACT

V.Owino@iaea.org

Study Design

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

Study Record Dates

• First Submitted: July 20, 2019
• First Posted: September 30, 2019
• Study Start: September 1, 2019
• Primary Completion: July 1, 2022
• Study Completion: December 1, 2022
• Last Updated: October 6, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1); AU (1); JA (1); PE (1); KE (1); IN (1); ZA (2); GB (1)