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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Children's Hospital Medical Center, Cincinnati
Sponsor:
Collaborator:
Universidade Federal do Ceara
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01832636
First received: April 12, 2013
Last updated: November 26, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Malnutrition
Environmental Enteropathy
Diarrhea
Dietary Supplement: Alanyl-Glutamine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intervention and Mechanisms of Alanyl-Glutamine for Inflammation, Nutrition, and Enteropathy (IMAGINE)

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Urinary Lactulose: Mannitol Intestinal Permeability Test [ Time Frame: Urine Collection on Day 1, 10-13, 30-37 ] [ Designated as safety issue: No ]
    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:
  • Fecal Lactoferrin Test [ Time Frame: Fecal sample collected on Day 1, 10-13, 30-37 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Fecal sample collected on Day 1, 10-13 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Measured and calculated Day 1, 10-13, 30-37, 90-104, 120-141 ] [ Designated as safety issue: No ]
    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.

  • Fecal Calorimetry [ Time Frame: Fecal sample collected on Day 1, 10-13, 30-37 ] [ Designated as safety issue: No ]
    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.

  • Metabolomic Profile of Urine [ Time Frame: Collected on Day 1, 10-13, 30-37 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1, 30-37, 90-104, 120-141 ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 140
Study Start Date: October 2013
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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.

  Eligibility

Ages Eligible for Study:   2 Months to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01832636

Contacts
Contact: Sean Moore, MD,MS 513-636-4415 Sean.Moore@cchmc.org

Locations
Brazil
Universidade Federal do Ceara Recruiting
Fortaleza, Ceara, Brazil
Contact: Aldo AM Lima, MD,PHD       alima@ufc.br   
Principal Investigator: Sean Moore, MD,MS         
Principal Investigator: Aldo Lima, MD,PHD         
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
  More Information

Publications:
Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01832636     History of Changes
Other Study ID Numbers: CIN001 -"IMAGINE"
Study First Received: April 12, 2013
Last Updated: November 26, 2013
Health Authority: Brazil: Ethics Committee

Keywords provided by Children's Hospital Medical Center, Cincinnati:
L-Alanyl-L-Glutamine
Environmental enteric dysfunction
Tropical enteropathy

Additional relevant MeSH terms:
Diarrhea
Inflammation
Intestinal Diseases
Malnutrition
Nutrition Disorders
Signs and Symptoms, Digestive
Signs and Symptoms
Pathologic Processes
Gastrointestinal Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on August 26, 2014