Intervention and Mechanisms of Alanyl-Glutamine for Inflammation, Nutrition, and Enteropathy

Phase 3

Completed

• Conditions: Environmental Enteropathy; Diarrhea; Malnutrition
• Interventions: Dietary Supplement: Alanyl-Glutamine

• Registration Number: NCT01832636
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

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?

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-04-12
• Study First Submitted QC: 2013-04-15
• Study First Posted: 2013-04-16
• Study Start: 2013-10
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-07
• Last Update Submitted: 2016-07-28
• Last Update Posted: 2016-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 112

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alanyl-Glutamine 3g/d	Alanyl-Glutamine	Alanyl-Glutamine orally 3g/day for 10 days
Alanyl-Glutamine 12g/d	Alanyl-Glutamine	Alanyl-Glutamine orally 12g/d for 10 days
Alanyl-Glutamine 6g/d	Alanyl-Glutamine	Alanyl-Glutamine orally 6g/day for 10 days
Glycine 12.5g/d	Alanyl-Glutamine	Glycine orally 12.5 g/d for 10 days. This dose is calculated to be isonitrogenous to 12g of Alanyl-Glutamine.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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).

Trial Locations

Locations (1)

Universidade Federal do Ceara; 🇧🇷 Fortaleza, Ceara, Brazil