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

Sponsor
Children's Hospital Medical Center, Cincinnati (Other)
Overall Status
Completed
CT.gov ID
NCT01832636
Collaborator
Universidade Federal do Ceara (Other)
112
1
4
26
4.3

Study Details

Study Description

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?

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: Alanyl-Glutamine
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
112 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Intervention and Mechanisms of Alanyl-Glutamine for Inflammation, Nutrition, and Enteropathy (IMAGINE)
Study Start Date :
Oct 1, 2013
Actual Primary Completion Date :
Dec 1, 2015
Actual Study Completion Date :
Dec 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Alanyl-Glutamine 3g/d

Alanyl-Glutamine orally 3g/day for 10 days

Dietary Supplement: Alanyl-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.
Other Names:
  • AminoStable (Ajinomoto)
  • Active Comparator: Alanyl-Glutamine 6g/d

    Alanyl-Glutamine orally 6g/day for 10 days

    Dietary Supplement: Alanyl-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.
    Other Names:
  • AminoStable (Ajinomoto)
  • Active Comparator: Alanyl-Glutamine 12g/d

    Alanyl-Glutamine orally 12g/d for 10 days

    Dietary Supplement: Alanyl-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.
    Other Names:
  • AminoStable (Ajinomoto)
  • Placebo Comparator: Glycine 12.5g/d

    Glycine orally 12.5 g/d for 10 days. This dose is calculated to be isonitrogenous to 12g of Alanyl-Glutamine.

    Dietary Supplement: Alanyl-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.
    Other Names:
  • AminoStable (Ajinomoto)
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Months to 5 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Universidade Federal do Ceara Fortaleza Ceara Brazil

    Sponsors and Collaborators

    • Children's Hospital Medical Center, Cincinnati
    • Universidade Federal do Ceara

    Investigators

    • Principal Investigator: Sean R Moore, MD, MS, Cincinnati Children´s Hospital
    • Principal Investigator: Aldo Lima, MD, PhD, Universidade Federal do Ceara

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Children's Hospital Medical Center, Cincinnati
    ClinicalTrials.gov Identifier:
    NCT01832636
    Other Study ID Numbers:
    • CIN001 -"IMAGINE"
    First Posted:
    Apr 16, 2013
    Last Update Posted:
    Aug 1, 2016
    Last Verified:
    Jul 1, 2016
    Keywords provided by Children's Hospital Medical Center, Cincinnati
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 1, 2016