Diarrhea, Environmental Enteropathy, Malnutrition
Conditions
Keywords
L-Alanyl-L-Glutamine, Environmental enteric dysfunction, Tropical enteropathy
Brief summary
Several host factors underlie the pathogenesis of the reciprocal cycle of childhood diarrhea and undernutrition in developing countries. These include intestinal inflammation, mucosal damage, and alterations in intestinal barrier function that lead to malabsorption, growth failure, and heightened susceptibility to recurrent and prolonged episodes of diarrhea. Recent studies from Northeast Brazil demonstrate the benefits of a novel alanyl-glutamine-based oral rehydration and nutrition therapy (Ala-Gln ORNT) in speeding the recovery of damaged intestinal barrier function in cell culture, animal models, patients with AIDS, and underweight children. Oral supplementation with Alanyl-Glutamine (Ala-Gln; 24g a day for 10 days) improves short-term gut integrity and weight velocity 4 months after therapy in a group of undernourished children from Northeast Brazil. Intervention and Mechanisms of Alanyl-Glutamine for Inflammation, Nutrition, and Enteropathy (IMAGINE) is a study designed to answer the following questions: 1) What is the lowest dose of Ala-Gln that improves intestinal barrier function, intestinal inflammation, and nutritional status in children at risk of underweight, wasting, or stunting? 2) What are the mechanisms by which Ala-Gln exerts these benefits?
Interventions
DIETARY_SUPPLEMENTAlanyl-Glutamine
Alanyl-Glutamine and Glycine doses will be prepared immediately prior to administration by dissolving in formula, milk, or fruit juice. Administration of each dose will be directly observed by a study nurse or health agent.
Sponsors
Universidade Federal do Ceara
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Months to 5 Years
Healthy volunteers
No
Inclusion criteria
1. Children who are undernourished or at risk of undernutrition, with anthropometric z-scores less than or equal to -1 for one of these parameters: height-for-age, weight-for-age, or weight-for-height. 2. Children ages 2 months to 5 years old.
Exclusion criteria
1. Children who are exclusively breastfed. 2. Have participated in another intervention study in the past two years. 3. Fever greater than 38.8 ° C. 4. Use of antibiotics. 5. Systemic disease or other serious medical condition (including, but not limited to meningitis, pneumonia, tuberculosis, and chickenpox). 6. Children who are unable to ingest, retain or absorb nutritional supplements. 7. Children whose families plan to move from the study area within the next 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Lactulose: Mannitol Intestinal Permeability Test | Urine Collection on Day 1, 10-13, 30-37 | Determine the dose-and time-effect of alanyl-glutamine on intestinal barrier function recovery using the intestinal permeability test, with measurement of the percentage of urinary excretion of lactulose, mannitol and ratio of lactulose:mannitol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fecal Cytokine Measurement | Fecal sample collected on Day 1, 10-13 | To evaluate the effect of alanyl-glutamine on intestinal inflammation, by measuring proinflammatory cytokines interleukin-1, interleukin-8, tumor necrosis factor-alpha (TNF), and regenerating gene 1B (REG1B) in stools of children at risk of undernutrition. |
| Anthropometry | Measured and calculated Day 1, 10-13, 30-37, 90-104, 120-141 | To evaluate the time and dose-effect of alanyl-glutamine on short and medium-term nutritional status by evaluating changes in anthropometric measures (z scores) over time: height-for-age, weight-for-age, and weight-for-height. |
| Fecal Lactoferrin Test | Fecal sample collected on Day 1, 10-13, 30-37 | To evaluate the effect of time and dose-response of alanyl-glutamine on intestinal inflammation, as measured by qualitative or quantitative testing for fecal lactoferrin in stools of children at risk of undernutrition. |
| Metabolomic Profile of Urine | Collected on Day 1, 10-13, 30-37 | To evaluate the time and dose-effect of alanyl-glutamine on metabolism in children at risk of undernutrition by means of urine metabolomic profile tests. |
| History of Diarrhea in the Previous Two Weeks | Day 1, 30-37, 90-104, 120-141 | History of diarrhea in the previous two weeks. A day of diarrhea will be defined as 3 or more looser than normal bowel movements in a 24-hour period. Distinct episodes must be separated by at least 2 days without diarrhea. Duration of episodes will be classified as acute (\< 7 days), prolonged acute (\>6 and \<14 days), or persistent (\>13 days). |
| Fecal Calorimetry | Fecal sample collected on Day 1, 10-13, 30-37 | To evaluate the effect of time and dose-response of alanyl-glutamine on the intestinal absorption of fat, protein, and carbohydrates, by measurement of fecal energy content by bomb calorimetry. |
Countries
Brazil
Outcome results
None listed