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NCT Number: NCT01832636

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

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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Key information

Conditions

Malnutrition Diarrhea Digestive System Diseases Environmental Enteropathy Gastrointestinal Diseases Intestinal Diseases Malabsorption Syndromes Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Digestive Sprue, Tropical

Age range

2 month–5 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Universidade Federal do Ceara

Fortaleza, Ceará, Brazil

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • Children ages 2 months to 5 years old.

Exclusion criteria

  • Children who are exclusively breastfed.
  • Have participated in another intervention study in the past two years.
  • Fever greater than 38.8 ° C.
  • Use of antibiotics.
  • Systemic disease or other serious medical condition (including, but not limited to meningitis, pneumonia, tuberculosis, and chickenpox).
  • Children who are unable to ingest, retain or absorb nutritional supplements.
  • Children whose families plan to move from the study area within the next 6 months.

Treatment and study plan

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.

Other names: AminoStable (Ajinomoto)

Primary outcomes

  1. Urinary Lactulose: Mannitol Intestinal Permeability Test

    Time frame: 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 outcomes

  1. Fecal Lactoferrin Test

    Time frame: 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.

  2. Fecal Cytokine Measurement

    Time frame: 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.

  3. Anthropometry

    Time frame: 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.

  4. Fecal Calorimetry

    Time frame: 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.

  5. Metabolomic Profile of Urine

    Time frame: 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.

  6. History of Diarrhea in the Previous Two Weeks

    Time frame: 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).

Sponsors and collaborators

Lead sponsor

Children's Hospital Medical Center, Cincinnati

Other

Collaborators

  • Universidade Federal do Ceara

Registry information

Official study title

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

Acronym: IMAGINE

Important dates

Study start
2013
Primary completion
2015
Study completion
2015
First posted
Apr 16, 2013
Registry last updated
Aug 1, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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