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| Name | Class |
|---|---|
| Universidade Federal do Ceara | OTHER |
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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?
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alanyl-Glutamine 3g/d | Active Comparator | Alanyl-Glutamine orally 3g/day for 10 days |
|
| Alanyl-Glutamine 6g/d | Active Comparator | Alanyl-Glutamine orally 6g/day for 10 days |
|
| Alanyl-Glutamine 12g/d | Active Comparator | Alanyl-Glutamine orally 12g/d for 10 days |
|
| Glycine 12.5g/d | Placebo Comparator | Glycine orally 12.5 g/d for 10 days. This dose is calculated to be isonitrogenous to 12g of Alanyl-Glutamine. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alanyl-Glutamine | Dietary Supplement | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Urine Collection on Day 1, 10-13, 30-37 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Fecal sample collected on Day 1, 10-13, 30-37 |
| Fecal Cytokine Measurement |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sean R Moore, MD, MS | Cincinnati Children´s Hospital | Principal Investigator |
| Aldo Lima, MD, PhD | Universidade Federal do Ceara | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universidade Federal do Ceara | Fortaleza | Ceará | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17325559 | Background | Lima NL, Soares AM, Mota RM, Monteiro HS, Guerrant RL, Lima AA. Wasting and intestinal barrier function in children taking alanyl-glutamine-supplemented enteral formula. J Pediatr Gastroenterol Nutr. 2007 Mar;44(3):365-74. doi: 10.1097/MPG.0b013e31802eecdd. | |
| 32826717 | Derived | Moore SR, Quinn LA, Maier EA, Guedes MM, Quetz JS, Perry M, Ramprasad C, Lanzarini Lopes GML, Mayneris-Perxachs J, Swann J, Soares AM, Filho JQ, Junior FS, Havt A, Lima NL, Guerrant RL, Lima AAM. Intervention and Mechanisms of Alanyl-glutamine for Inflammation, Nutrition, and Enteropathy: A Randomized Controlled Trial. J Pediatr Gastroenterol Nutr. 2020 Sep;71(3):393-400. doi: 10.1097/MPG.0000000000002834. |
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| ID | Term |
|---|---|
| D044342 | Malnutrition |
| D003967 | Diarrhea |
| D013182 | Sprue, Tropical |
| ID | Term |
|---|---|
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| C054122 | alanylglutamine |
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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. |
| 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. | 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. | 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. | 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). | Day 1, 30-37, 90-104, 120-141 |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008286 | Malabsorption Syndromes |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D008659 | Metabolic Diseases |