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

July 28, 2016 updated by: Children's Hospital Medical Center, Cincinnati

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

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?

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

112

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • Ceara
      • Fortaleza, Ceara, Brazil
        • Universidade Federal Do Ceara

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 months to 5 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Urine Collection on Day 1, 10-13, 30-37

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Fecal sample collected on Day 1, 10-13, 30-37
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.
Fecal sample collected on Day 1, 10-13
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.
Measured and calculated Day 1, 10-13, 30-37, 90-104, 120-141
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.
Fecal sample collected on Day 1, 10-13, 30-37
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.
Collected on Day 1, 10-13, 30-37
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).
Day 1, 30-37, 90-104, 120-141

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

Universidade Federal do Ceará

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2013

Primary Completion (ACTUAL)

December 1, 2015

Study Completion (ACTUAL)

December 1, 2015

Study Registration Dates

First Submitted

April 12, 2013

First Submitted That Met QC Criteria

April 15, 2013

First Posted (ESTIMATE)

April 16, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

August 1, 2016

Last Update Submitted That Met QC Criteria

July 28, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIN001 -"IMAGINE"

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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