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?
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
112
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.
Universidade Federal do Ceara
Fortaleza, Ceará, Brazil
Urinary Lactulose: Mannitol Intestinal Permeability Test
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.
Time frame: Urine Collection on Day 1, 10-13, 30-37
Fecal Lactoferrin Test
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.
Time frame: Fecal sample collected on Day 1, 10-13, 30-37
Fecal Cytokine Measurement
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.
Time frame: Fecal sample collected on Day 1, 10-13
Anthropometry
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.
Time frame: Measured and calculated Day 1, 10-13, 30-37, 90-104, 120-141
Fecal Calorimetry
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.
Time frame: Fecal sample collected on Day 1, 10-13, 30-37
Metabolomic Profile of Urine
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.
Time frame: Collected on Day 1, 10-13, 30-37
History of Diarrhea in the Previous Two Weeks
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).
Time frame: Day 1, 30-37, 90-104, 120-141
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