Enteropathy, Glucose-Galactose Malabsorption, Intestinal Permeability, Linear Growth Failure, Malnutrition, Child
Conditions
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.
Interventions
None listed
Sponsors
International Atomic Energy Agency
Flinders University
International Centre for Diarrhoeal Disease Research, Bangladesh
St. John's Research Institute
The University of The West Indies
Mmust Masinde Muliro University of Science and Technology
Asociacion Benefica Prisma
Scottish Universities Environmental Research Centre
University of Michigan
Tropical Diseases Research Centre, Zambia
Gastroenterology Services, Ltd.
University of Virginia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Months to 15 Months
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the relationship between SBT and childhood linear growth | 6 months after enrollment is completed | 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 |
| Comparison of SBT to Lactulose rhamnose (LR) test- time to 50% recovery | 6 months after enrollment is completed | 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) |
| Correlation of SBT (% recovery at 90 minutes) to Lactulose rhamnose (LR) test-Lactulose recovery | 6 months after enrollment is completed | 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 |
| Correlation of SBT (time to 50% recovery) to Lactulose rhamnose (LR) test-Lactulose recovery | 6 months after enrollment is completed | 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 |
| Correlation of SBT (% dose recovered at 09 minutes) to Lactulose rhamnose (LR) test-Mannitol recovery | 6 months after enrollment is completed | The 13C-SBT (cumulative percent of dose of 13C recovered at 90 minutes post administration) will be compared to percent mannitol recovery |
| Correlation of SBT (time to recovery of 50% of dose) to Lactulose rhamnose (LR) test-Mannitol recovery | 6 months after enrollment is completed | The 13C-SBT (time to 50% area under the curve 13C tracer, expressed in minutes) will be compared to percent mannitol recovery |
| Characterize the relationship between SBT (% of dose recovered at 90 min) and baseline childhood anthropometrics (attained length) | 6 months after enrollment is completed | 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) |
| Characterize the relationship between SBT (time to recovery of 50% of dose) and baseline childhood anthropometrics (attained length) | 6 months after enrollment is completed | 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) |
| Characterize the relationship between SBT and childhood anthropometrics (attained weight) | 6 months after enrollment is completed | 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) |
| Characterize the relationship between SBT and childhood anthropometrics (attained weight for height) | 6 months after enrollment is completed | 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) |
| Characterize the relationship between SBT (time to 50% recovery of 13C) and childhood linear growth, 3 months | 6 months after enrollment is completed | 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 |
| Characterize the relationship between SBT and childhood linear growth, 6 months | 6 months after enrollment is completed | 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 |
| Characterize the relationship between SBT (% dose recovered at 90 min)and childhood linear growth, 3 months | 6 months after enrollment is completed | 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 |
| Comparison of SBT to Lactulose rhamnose (LR) test-% dose 90 min | 6 months after enrollment is completed | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the relationship between the 13C-SBT (% recovery at 90 minutes) and kynurenine tryptophan ratio, | Six months from the enrollment of the last subject | Compare 13C SBT as measured by % recovery of 13C probe at 90 minutes with kynurenine tryptophan ratio |
| Assess the relationship between the 13C-SBT as assessed by percent of 13C tracer recovered in at 90 minutes and fecal alpha-antitrypsin concentration | Six months from the enrollment of the last subject | Compare 13CSBT as measured by the percent of tracer recovered at 90 minutes with fecal anti-trypsin concentration (mg/g) |
| Assess the relationship between the 13C-SBT as measured by the time to 50% recovery of 13C and fecal alpha-antitrypsin | Six months from the enrollment of the last subject | Compare 13C SBT as measured by the time to 50% recovery of 13C with fecal anti-trypsin concentration (mg/g) |
| Assess the relationship between the 13C-SBT (% recovery 90min) and fecal myeloperoxidase | Six months from the enrollment of the last subject | Compare fecal myeloperoxidase concentration (ng/mL) with 13SBT (% of cumulative dose recovered at 90 minutes, expressed as %) |
| 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 | Compare fecal myeloperoxidase concentration (ng/mL) with 13SBT (time to recovery of 50% of the administered 13C tracer, measured in minutes) |
| 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 | Compare serum fatty acid binding protein concentration (ng/mL), with 13SBT as assessed by % of administered dose recovered at 90 minutes |
| 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 | Compare serum fatty acid binding protein concentration (ng/mL) with 13SBT as measured by the time (in minutes) to the recovery of 50% of the administered dose of 13C. |
| Assess the relationship between the 13C-SBT (time to 50% recovery) and kynurenine tryptophan ratio | Six months from the enrollment of the last subject | Compare time to recovery of 50% of 13C probe of SBT with kynurenine tryptophan ratio (molar ratio of KT multiplied by 1000) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Reproducibility of the 13C-SBT test , percent of dose recovered in first 90 minutes | Six months from the enrollment of the last subject | We will assess the coefficient of variation and correlation coefficient between repeated cumulative percent of dose recovered at 90 minutes post administration on separate SBT tests administered one week apart done on the same child (Peru site only). |
| Epidemiologic factors that influence 13C-SBT measure, percent of dose recovered at 90 minutes | Six months from the enrollment of the last subject | Determine if significant associations exist between 13C-SBT measured as cumulative percent of dose recovered at 90 minutes post administration and the WAMI index.The WAMI index is a previously validated composite index of environmental variables to create a index that expresses the socioeconomic and physical environment in diverse geographical contexts (PMID 24656134) |
| Epidemiologic factors that influence 13C-SBT measure, time to 50% AUC recovered | Six months from the enrollment of the last subject | Determine if significant associations exist between 13C-SBT measured as the time to recovery of 50% of the administered tracer and the WAMI index. The WAMI index is a previously validated composite index of environmental variables to create a index that expresses the socioeconomic and physical environment in diverse geographical contexts ((PMID 24656134). |
| 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 | We will assess the coefficient of variation and correlation coefficient between repeated SBT tests 7 days apart as assessed by the time to 50% area under the curve of 13C tracer, expressed in minutes from the same child (Peru site only). |
Countries
Australia, Bangladesh, India, Jamaica, Kenya, Peru, United Kingdom, Zambia
Contacts
Primary ContactMargaret N Kosek, MD
Backup ContactVictor Owino, PhD
Outcome results
None listed